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NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
Amivantamab (Rybrevant): CADTH Reimbursement Review: Therapeutic area: Non–small cell lung cancer [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2023 May.
Lung Cancer Canada is a registered national charitable organization that serves as Canada’s leading resource for lung cancer education, patient support, research and advocacy. Lung Cancer Canada is a member of the Global Lung Cancer Coalition and is the only organization in Canada focused exclusively on lung cancer. https://www.lungcancercanada.ca/
Lung Cancer Canada is registered with CADTH.
The information discussed throughout this submission consists of the thoughts and experiences of non-small cell lung cancer patients and caregivers, conducted through phone interviews by Lung Cancer Canada. All data was collected in May 2022.
EGFR NSCLC is a relatively common mutation within non-small cell lung cancer (NSCLC); however, exon 20 insertion mutations as per this indication are very rare within the EGFR realm, making up between 0.1 – 4% of all NSCLC cases, and amivantamab is a relatively new therapy given NOC/c by Health Canada just in May 2022. All of the patients interviewed are EGFR positive, though only 2 of 4 patients are EFGR Exon 20 patients. All are currently part of the amivantamab clinical trial in Ontario.
Demographic Data.
Prior to diagnosis, 63-year-old SP was extremely active and was always outdoors as she owns a landscaping business and routinely helps with gardening, landscaping, and designs. Living a healthy lifestyle and as a never-smoker, SP was constantly on-the-go and the thought of lung cancer never crossed her mind. However throughout early fall of 2021, SP developed a persistent cough and tried to treat it with a steroid puffer, but when things hadn’t improved over the next several weeks, something felt amiss. She insisted on an x-ray to rule out pneumonia, but instead, she was shocked to find out there was a mass in her lung, diagnosing her with stage 4 non-small-cell lung cancer, with EGFR Exon 20 insertion mutation. Her entire family, including her three adult children, was shocked to find the news, and it was extremely tough for SP to process herself as well, even until this day.
SP recalls, “it was incredibly shocking to hear the words ’lung cancer’ come out of the doctor’s mouth. I didn’t know what to do, it felt like time had stopped.” As hospital visits became more frequent once she started treatment with maintenance chemotherapy and amivantamab, she had to put her business on hold while still dealing with the emotional implications of her diagnosis. When patients like SP are handed a diagnosis, patients expect to hear what treatment options are available for them next. However, for patients with EGFR Exon 20 NSCLC, treatment options that are precise and specific to their disease are extremely limited, and there is a significant unmet need in this population. There are currently no targeted therapies specific to EGFR Ex20, until now. SP has started her treatment with amivantamab in December 2021 and continues to be on it as of May 2022 and has seen significant improvements in not only her physical health, but also her mental health.
8 years ago in early 2014, then 56-year-old JQ had some back pain and a cough that didn’t seem to go away for months, but simply thought it was due to his blood pressure medication. After he felt breathless after walking up one flight of stairs, he felt something was off and decided to head to his primary care doctor. A few tests and scans later, it was discovered he had lesions in his lower back, spine, and bones, which was traced back to the primary tumor in the lung, thus diagnosing JQ with stage 4 NSCLC in July 2014. After working as a physician in the army for 2 decades, he was faced with a number of patients with serious conditions, but when it became personal, it was hard to digest for not only himself but also his family.
JQ recalls, “When I was first given a diagnosis with stage 4 lung cancer, I felt like I had hit a dead end and didn’t think I’d even make it to the next Christmas, but then I did make it, and then to my next birthday, then Christmas, then each Christmas after that. It has been 8 Christmases and 8 birthdays since I got first diagnosed, and I feel eternally grateful I got this extra time.” Thanks to targeted therapies like amivantamab that are paving the way for patients to have increased quality of life and survivorship with advanced disease, JQ continues to be on amivantamab in May 2022 with a good quality of life and improvements in his disease and is hopeful he’ll continue to celebrate each birthday and each Christmas in the foreseeable future.
Lung cancer represents the highest incidence and prevalence of all cancers in Canada (in men and women), with an estimated 29,800 incident cases in 2020. Approximately 85% of cases are identified as the non-small cell subtype, and 15% of cases are small cell. Moreover, it is the leading cause of cancer-related mortality, with a 19% overall 5-year survival rate in 2020 (Burnett et al., 2021). Mutations in the epidermal growth factor receptor (EGFR) gene are among the most common targetable genomic drivers of non-small cell lung cancer (NSCLC). 90% of the EGFR mutations comprise of EGFR exon 19 deletion and exon 21 L858R mutation, while EGFR exon 20 insertions (EGFR Ex20Ins) are much less common, with a frequency of 0.1 - 4% in NSCLC (Burnett et al., 2021). Patients with EGFR Ex20 mutations have a poorer prognosis as conventional TKIs have poor efficacy in a majority of EGFR Ex20Ins subtypes. Chemotherapy remains the current standard of care for advanced NSCLC patients with this mutation. However, targeted therapy has since emerged as an important mean of disease management for NSCLC patients with a targetable mutation, including EGFR. This form of treatment has greatly improved patient outcomes and quality of life and is now a treatment option that is some patients’ only hope. It has seen incredible success and has allowed patients like SP and JQ a chance at survivorship and a livelihood that is nearly comparable to before diagnosis, something that they may never had thought would be possible before.
Amivantamab is a targeted therapy used to treat NSCLC for EGFR Exon 20 mutations and was given Notice of Compliance by Health Canada very recently in May 2022. It has shown promising results in efficacy and progression-free survival through the CHRYSALIS study, with median PFS of 8.3 months, overall response rate of 43.2%, and median overall survival of 22.8 months (Park et al., 2021). Time is extremely valuable for this subset of patients, and with the promising improvements amivantamab has seen to give patients within this population, it makes all the difference in their quality of life and livelihood. The treatment options for patients with this uncommon EGFR subtype are limited, with amivantamab being the first targeted therapy to be approved for this patient population in Canada, and one of only two Ex20Ins treatments approved by the US FDA (Park et al., 2021). Patients deserve treatment options that are effective beyond the current standard of care, and amivantamab has an incredible amount of potential to drive the pathway for future lung cancer treatment for thousands of Canadians. Lung Cancer Canada strongly encourages CADTH to take this into consideration for amivantamab to be reimbursed as it would lead the pathway to new developments, new treatments, improvements in accessibility, and better affordability for lung cancer patients across the country.
The current standard of care for patients with NSCLC driven by EGFR exon 20 mutations is chemotherapy. Chemotherapy has been a long-standing and well-documented standard of care for lung cancer patients and has seen some benefits. However, it is limited as a viable long-term treatment option due to its nature as a systemic treatment with harsh and toxic side effects, which often creates additional burdens on patients, leading to decreased functionality and increased dependence on caregivers in daily activities without bringing much benefit or efficacy in treating disease. It also limits their ability to remain flexible in returning to work or continuing their hobbies, and thus, a more viable treatment option is necessary. Thus, chemotherapy typically only used as a first-line treatment option in this population, with limited mutation-specific options beyond first line.
Although the patients interviewed for this submission did not have experience on chemotherapy, most were offered chemotherapy as a back-up option should they not choose to take part in the amivantamab clinical trial. For example, JQ’s oncologist reassured him that chemotherapy was always an option, but rather as a last resort should other treatments not be effective. LC was offered a choice between chemotherapy or the amivantamab clinical trial and chose to move forward with amivantamab. SP is currently on combination amivantamab alongside maintenance chemotherapy; her experience is highlighted in Section 6. The experiences of patients on chemotherapy are well documented and discussed in previous Lung Cancer Canada submissions. It should be noted that patients treated with adjuvant chemotherapy still relapse, showing this form of treatment is not effective at preventing recurrence or keeping patients disease-free.
Some patients had experience with other targeted therapies for the EGFR mutation prior to treatment with amivantamab, though they do not have the specific Exon 20 mutation, rather other EGFR mutations. These therapies have been used to treat patients with other EFGR mutations and did have some success in keeping their disease stable but were limited in its effectiveness to target their mutations. Specifically for EGFR exon 20 mutations, there are no current treatment options that are precise and targeted to the genetic mutation, which leads to the significant unmet need within this group.
There have been many incredible advancements in recent years for lung cancer treatment that have changed the paradigm for patients. While EGFR mutations being amongst the most common targetable drivers of non-small cell lung cancers, prevalent in roughly 38% of NSCLCs, EGFR Ex20 mutations are one of the rarest amongst this group, with exon 20 mutations accounting for only 3.8% of EGFR adenocarcinomas (Yoon et al., 2020). As a result, there have not been many opportunities for the development and refinement of new targeted therapy treatments for this specific subset of NSCLC patients, until now. It has been seen that targeted therapies for EGFR-driven NSCLC have been met with incredible success that gives patients their livelihoods back, allows them to hope for a better tomorrow and plan further down the line for a possible future. These outcomes play an integral role in the goals patients have in their treatment decisions, including:
Experience With Drug Under Review.
Amivantamab is effective at treating patients’ disease.
By the time JQ started treatment with amivantamab, his disease had progressed in that he had a lesion in his brain and mets in his bones, in addition to the primary tumour in his lung. Although the treatment did not necessarily shrink the tumours, it was very effective at maintaining stability in his tumours and metastases, which is a feat in itself. The mets in his bones and lung have continued to be stable without any additional growth in the 14 months he has been on the treatment, which is a positive step. However, amivantamab does not cross the blood-brain barrier, so JQ has developed 6 metastases in his brain while on the therapy, compared to the one met when he started. He is hopeful he will be able to stay on the treatment for longer, while his oncologist continues to look into other treatments that are able to treat his brain mets.
Once SP was diagnosed in October 2021 with stage 4 EGFR Exon 20 insertion non-small cell lung cancer, she started on combination chemotherapy and amivantamab in December as her first line of treatment and has already seen improvements in her disease symptoms in the few months since. Within the first few sessions, she felt a noticeable difference as her cough is completely gone, no shortness of breath, and her tumours are responding well according to her oncologist.
LT was diagnosed July 2021 with stage 4 NSCLC with EGFR Exon 20 in both lungs, but fortunately did not have any metastases at diagnosis. She started on first-line treatment with amivantamab in January 2022, and after roughly 5 sessions, her scans have already showed shrinkage in the lung shadows within her scans. As this is her first treatment for her cancer, her oncologist is hopeful she can continue to stay on the treatment for the foreseeable future.
When LC started her treatment with amivantamab, the clinicians said she had responded to the treatment much quicker than most other participants. As of May 2022, about 1.5 years after starting her treatment, all of her tumours and metastases have shrunk and are much smaller than at treatment onset. They have all remained stable and relatively small ever since.
The side effects of amivantamab are manageable with minimal impact on daily life.
As per the CHRYSALIS clinical study, the most common treatment-related adverse events were rash, inflammation of the nailbed, hypoalbuminemia, swelling of the mouth lining, diarrhea, constipation, and nausea (Park et al., 2021). These side effects are all relatively manageable and do not impede the quality of life of patients as much as traditional systemic therapies do, as is the current standard of care for patients with EGFR Ex20 mutations after first-line treatment.
Amongst the patients LCC interviewed for this submission, the aforementioned side effects correspond to what was reported by patients. The main adverse event patients experienced was issues with the skin, including inflammation of the nailbed, rashes on the face and legs, acne, and dry and sensitive skin. Other side effects that were reported include severe dry mouth, slight vision deterioration, severe muscle pain the first few days after treatment, fatigue, chronic constipation, and yeast infections. For SP specifically, she has had tinnitus for about 10 years even prior to her cancer diagnosis due to a bicycle accident, but amivantamab has caused the pitch to change throughout treatment, which was a tough adjustment. However, all patients mentioned the side effects they’ve had are manageable and do not have much impact their ability to go about their livelihoods. Some patients mentioned that although the side effect burden was more than what they had experienced with other targeted therapies in the past, they would not consider discontinuing treatment as the hope of survival outweighs the negatives.
Amivantamab has given patients additional treatment options when they’ve exhausted other options.
Both LC and JQ are currently being treated with amivantamab as their 3rd line of treatment, and both have used other targeted therapies in the past. When LC’s oncologist mentioned she had progressed on her 2nd cancer treatment with osimertinib in November 2020, chemotherapy was most likely the only other option left, and without treatment, LC would have only about 6 months left. LC recalls it felt like she had hit a dead end because of the lack of treatment options that were available for her specific EGFR mutation.
Similarly, for JQ, after he was also on osimertinib for nearly 5 years progression-free, it was hard to accept when he had progressed afterwards in late 2020. JQ mentions that amivantamab was a genuine lifesaver for himself and other patients who have no other option left. He qualified for the clinical trial after a biopsy revealed he had the cMET amplification, which he felt like a weight had been lifted off him because there was still a potential targeted treatment available. As the indication for this submission is for patients with advanced or metastatic disease, they are often faced with limited treatment options because of the lack of available targeted therapies in this patient population. Amivantamab will be the first drug in this exon 20 EGFR space, giving patients the opportunity to have a treatment that is specific and targeted to their disease. Having this opportunity is critical for specificity in treatment options, and there is a significant unmet need for novel targeted therapies that will prolong progression-free survival and improve quality of life for these patients. Amivantamab has the ability to change this.
Patients on amivantamab enjoy a quality of life and level of functionality that is similar to pre-diagnosis.
When LC was first diagnosed in late 2018, she was very weak and needed help from her son, who was about to finish grade 12 at the time. She was so ill that she could not take care of him or herself and needed to depend on her close friends and relatives for basic tasks around the house, including grocery shopping, cooking meals, cleaning, and doing the laundry. She recalls, “At my weakest, they became my strength. Without them, I don’t know how I would have gotten through that moment in time. Since then, they have stood by me – through all of the highs and lows”. When she started on amivantamab, she already started to feel better within 2 months. She has been able to maintain her functionality throughout all of her past cancer treatments, but amivantamab has further accelerated the activities she has been able to do. When she just started amivantamab, she was physically unwell and very weak and needed a lot of help from relatives and friends. She couldn’t drive herself to complete daily errands and required relatives’ help, but now she is able to travel to Toronto for treatments every 2 weeks via public transit and has started driving again while back in her hometown. She has returned to exercising at the gym every single day now after starting treatment, started swimming laps at the pool again, and return to the relatively active lifestyle she was used to. LC is grateful she never had any severe physical impairments that impeded her going about basic tasks but attributes the accelerated return to a quality of life she had before diagnosis from amivantamab.
As amivantamab is SP’s first line of treatment, the success she found with the treatment has allowed her to continue to maintain her independence throughout treatment and continues to be able to do all her activities of daily living that she could prior to diagnosis 7 months ago. As she was a self-employed landscaper, her days mainly consisted of physical labour outdoors, and although she was unable to do much in the first few days after her treatment due to the side effects, she is able to continue helping out with minor gardening and landscaping work as needed for her business and stays active outdoors whenever she feels well. SP is grateful she does not yet have any severe physical impairments because of her cancer so far and is hopeful amivantamab will continue to maintain her independence, functionality, and health-related quality of life.
Since starting the amivantamab clinical trial, JQ travels 4-5 hours across the province every 2 weeks for his treatment, which he coined as “the closest he’s gotten to travelling and being on vacation for the last 8 years”. After he developed further metastases in his brain while on amivantamab, he hasn’t been able to drive long distances and has his son drive each trip instead. However, he still continues to drive while in his hometown and can go about his daily life with some normalcy. He has absolutely no problems when sitting down and is able to go about his day-to-day life running errands like grocery shopping, cooking, cleaning the house, and doing physical activity with no issues. Although he can’t do more intense activities like mowing the lawn or shoveling the snow, JQ feels like amivantamab has given him a great quality of life nonetheless.
When LT was first diagnosed in July 2021, the only symptom of her disease she had was a persistent cough that never went away for months, and only insisted on going back to the doctors when she coughed up blood one day. She had been retired 20 years prior and was living a fulfilling life after immigrating to Canada in 1997, spending time with friends, family, travelling, attending dance and Zumba classes, and being active outdoors. After being diagnosed during the pandemic and subsequent treatment with amivantamab, she had to put a halt to the gym and dance activities, but because the nature of amivantamab does not impose side effects as harsh as other traditional systemic treatments, LT has been able to continue exercising at home and even continue working as a school bus driver every single day for over a decade even after retirement. She drives around the city every day, has no issues running errands like grocery shopping, taking public transit to meet with friends, shopping, and visiting her daughter and son-in-law nearly every weekend. The flexibility that amivantamab has as a targeted therapy with minimal and manageable side effects on patients like LC, LT, and SP allows patients to continue enjoying the hobbies they love and have a worthwhile quality of life.
Amivantamab has given patients a hope for the future and allowed them to make longer term goals.
When LC was diagnosed in late 2018, her son was just finishing grade 12 and as a single mother, she was immediately faced with thoughts about if he would be okay in the worst-case scenario. With a stage 4 diagnosis, these thoughts are unfortunately common in cancer patients with advanced disease like LC’s. However, after seeing the success and effectiveness amivantamab has had on her disease, her mindset has since been filled with hope and excitement. When asked by Lung Cancer Canada about her goals for the future, LC was excited to share she has been able to make short and long term goals alike – to see her son graduate from university next year, and further down the line, hopes that she has a shot at being there when he gets a full-time job, when he gets married, settles down and starts a family, and maybe even be there to meet her grandchildren.
SP has been on amivantamab for about half a year since December 2021, and when she was diagnosed with stage 4 disease, she was shocked as lung cancer was the last thing on her mind being a healthy and very active individual. With three adult children living their own lives, her entire family was shocked to say the least when she was told her prognosis wasn’t looking good. After about 6 months of starting treatment with amivantamab. SP noticed her mindset has improved since the initial shock but is still dealing with emotional implications of diagnosis and treatment. Although she doesn’t have any pressing hopes for her future at the moment, her motivation to keep going stems from “staying alive until the next treatment option”. Her youngest son will be getting married this fall, so she hopes to be around for that. Patients like SP and LC are able to maintain a relatively optimistic mindset thanks to amivantamab and allows patients to continue to have a sense of hope for the future.
Amivantamab has given some patients the flexibility to return to work, even after retirement.
76-year-old LT had already been retired for nearly 20 years when she was diagnosed in 2021, but that did not keep her away from her job for long. 5 years after she retired, she went back to her job as a school bus driver and has continued to drive and work every school day since for the last 16 years, even though her cancer diagnosis and journey. As amivantamab was her first line of treatment after diagnosis, the success and effectiveness she had with the therapy has allowed her to maintain her quality of life, independence, functionality, and livelihood in that she still drives the buses every morning and afternoon rush without needing much time off. LT repeatedly mentioned to LCC that she absolutely is still in love with her job and it’s also a great distraction from her disease while keeping her engaged in the community. It has allowed her to keep herself busy and distracted from the anxiety that would otherwise ensue if she continued to be at home all day, especially evident when schools were closed during the COVID-19 pandemic. LT foresees herself continuing to drive the school bus everyday as long as she is able to, and thanks to amivantamab, she’s able to maintain a relatively “normal” livelihood that she absolutely enjoys and finds worthwhile and fulfilling.
SP had to put her landscaping business on hold for two months at the beginning of treatment with amivantamab because her hospital visits were frequent but has since returned to working throughout her treatment when she’s able to. She did hire additional help to complete remaining contracts and is no longer taking any new projects but getting out of the house and tying up loose ends before her business is scheduled to close in June 2022 gives her a sense of relief.
Patients with EGFR Exon 20 insertions are identified using Next Generation Sequencing (NGS). NGS is routinely conducted in all patients with advanced NSCLC with a non-squamous and squamous histology, without a smoking history.
There is a huge unmet need with this population of NSCLC EGFR Exon 20 mutation patients as there is currently no targeted treatment available, and rather the current standard of care continues to be systemic treatments like chemotherapy. This population is so rare and there are very few treatment options for these patients, yet patients are desperate for a treatment that works with specificity. Amivantamab is an exciting option for targeting this mutation and has the opportunity to be the first targeted therapy to be approved in this population. It is seen to be effective at treating disease, allows patients to continue living a worthwhile quality of life, has manageable side effects, and even allowed some to return to work. Clinical data from the CHRYSALIS study have shown promising results, with median progression-free survival at 8.3 months, overall response rate of 43.2%, and median overall survival of 22.8 months (Park et al., 2021). There are also ongoing clinical trials of amivantamab in NSCLC EGFR Ex20ins in the first line setting, which have been showing promising results as seen with first-line patients LT and SP above.
There is a significant unmet need for novel targeted therapies that will prolong progression-free survival and improve health-related quality of life for patients with EGFR Exon 20 insertions, but amivantamab has the opportunity to change this. Lung Cancer Canada strongly pushes CADTH to recognize this gap and barrier in adequate treatment options that are specific to these patients who deserve treatments that will work and increase the accessibility of these treatment for patients across Canada. LCC is hopeful that this may become the new standard of care in this disease for second line treatment and beyond, and patients in this setting are not faced at a “dead end” when treatment with other TKIs or chemotherapy are no longer effective.
References
Burnett, H., Emich, H., Carroll, C., Stapleton, N., Mahadevia, P., & Li, T. (2021). Epidemiological and clinical burden of EGFR Exon 20 insertion in advanced non-small cell lung cancer: A systematic literature review. PloS one, 16(3), e0247620. DOI: 10.1371/journal.pone.0247620
Park, K., Haura, E. B., Leighl, N. B., Mitchell, P., Shu, C. A., Girard, N., ... & Cho, B. C. (2021). Amivantamab in EGFR exon 20 insertion-mutated non-small-cell lung cancer progressing on platinum chemotherapy: Initial results from the CHRYSALIS phase I study. Journal of Clinical Oncology, 39 (30). 3391-3402. DOI: 10.1200/JCO.21.00662
Yoon, H. Y., Ryu, J. S., Sim, Y. S., Kim, D., Lee, S. Y., Choi, J., Park, S., Ryu, Y. J., Lee, J. H., & Chang, J. H. (2020). Clinical significance of EGFR mutation types in lung adenocarcinoma: A multi-centre Korean study. PloS one, 15(2), e0228925. DOI: 10.1371/journal.pone.0228925
To maintain the objectivity and credibility of the CADTH reimbursement review process, all participants in the drug review processes must disclose any real, potential, or perceived conflicts of interest. This Patient Group Conflict of Interest Declaration is required for participation. Declarations made do not negate or preclude the use of the patient group input. CADTH may contact your group with further questions, as needed.
Did you receive help from outside your patient group to complete this submission? If yes, please detail the help and who provided it.
No.
Did you receive help from outside your patient group to collect or analyze data used in this submission? If yes, please detail the help and who provided it.
No.
List any companies or organizations that have provided your group with financial payment over the past 2 years AND who may have direct or indirect interest in the drug under review.
Financial Disclosures for Lung Cancer Canada.
The Ontario Lung Association (now named Lung Health Foundation) is registered with the CADTH and pCODR (www.lunghealth.ca). The Lung Health Foundation (Ontario Lung Association) is a registered charity that assists and empowers people living with or caring for others with lung disease. It is a recognized leader, voice and primary resource in the prevention and control of respiratory illness, tobacco cessation and prevention, and its effects on lung health. The Foundation provides programs and services to patients and health-care providers, invests in lung research and advocates for improved policies in lung health. It is run by a board of directors and has approximately 46 employees, supported by thousands of dedicated volunteers.
The information provided from the Lung Health Foundation in this submission was obtained from an online survey and three phone interviews that were conducted between September and December 2021. The interviews were with two female patients and one male patient living with lung cancer. All the patients interviewed were over the age of 50. One of the female patients is based in Ontario and the other patient is based in Manitoba. The male patient was from Quebec. There were 2 survey respondents and demographic data was not collected. Input from a Registered Nurse is also included based on information gathered from monthly support groups attended by patients and their caregivers. Input from a certified respiratory educator was also obtained for this submission. The individual reviewed sections related to disease experience, experiences with available treatments and outcomes.
Patients interviewed expressed that they found it difficult to cope with a lung cancer diagnosis. Lung cancer is associated with a poor prognosis and is the leading cause of cancer related deaths (Canadian Cancer Statistics, 2021). The patients interviewed report that the symptoms they experience with lung cancer were, in most cases, mild and are often associated with other conditions which led to a late diagnosis. The symptoms reported were shortness of breath, fatigue and pain. One patient interviewed, reported that she had a lingering cough for over six months before she was screened for lung cancer. She had been considered low risk because she did not have a smoking history. Another patient interviewed reported that she received her diagnosis during the peak of the COVID-19 pandemic. Delays in getting diagnostic tests and starting treatment was a great source of distress for her. Patients found the psychosocial effects of having a disease with a poor prognosis challenging and they also struggled with side effects associated with some treatments.
Some of the psychosocial effects reported were anxiety (66%), distress (100%) and depression (66%). One patient reported that having lung cancer was particularly isolating because of the stigma associated with lung cancer. She withdrew from all activities because she did not want people to know that she was diagnosed with lung cancer. Another patient interviewed described having a challenging time maintaining relationships with families and friends. They felt short tempered and impatient. Physical and emotional intimacy were also reported to be a challenge.
The side effects related to some treatments severely impact day to day and quality of life. One of the patients interviewed reported that he struggled with the side effects of chemotherapy. Prior to starting treatment, he was active and played sports, but once he started chemotherapy, he was unable to participate in his usual activities. He reported having hair loss, loss of appetite, weight loss, poor sleep, difficulty breathing, and this severely impacted his quality of life. This was very challenging for him. He also reported that the hair loss impacted his self-esteem because he looked visibly ill.
Another patient interviewed, reported that she experienced neuropathy, difficulty swallowing, fatigue and scarring in her lungs resulting in breathing difficulties. This negatively impacted her quality of life and ability to work and care for her family.
Family members and caregivers of those living with lung cancer share the same psychosocial burdens as the patients. They also have the added responsibility of providing care. Being a caregiver affects their ability to work, their relationships with family and friends and their emotional well-being. Their independence and ability to travel and socialize are often impacted as well. Having to take time off work to drive those they are caring for to get groceries, run errands or attend medical appointments can be problematic for caregivers. Feelings of fatigue and emotional exhaustion are not uncommon.
The treatments tried by the respondents’ included surgery, radiation, chemotherapy, targeted therapy and immunotherapy. The medications tried included Cisplatin, Docetaxel, Gefitinib, Entrectnib, Alectinib, Brigatinib, Opdivo+Yervoy and Tagrisso.
The benefits experienced with the treatments were prolonged life, delayed disease progression and a reduction in the severity of disease-related symptoms. Although these benefits were noted, most patients struggled with lingering side effects. Respondents who received surgery, reported deconditioning and chronic fatigue. Some of the side effects reported from radiation were fatigue, skin changes, hair loss and tissue scarring.
With oral and subcutaneous medications, the side effects reported included fatigue, nausea, vomiting, mood changes, diminished appetite, weight loss, hair loss, anemia, hypothyroidism and neuropathy. Side effects from chemotherapy severely impacted the patients’ quality of life, ability to work and in some cases, the ability to perform activities of daily living.
When asked about challenges with access to treatment, the respondents reported that they struggled with the cost of treatments and navigating the healthcare system. Some respondents reported travelling several hours to access treatments and sometimes they needed to stay overnight in hotels. This added a financial burden to the treatment process.
Patients also found delays in treatment and diagnostic testing to be a great source of distress because lung cancer progresses quickly, and advanced disease is associated with poorer outcomes.
Patients are looking for medications that are effective in curing lung cancer. Patients are most interested in medications that “cure versus treat”. Patients discussed the mental burden that comes from living with lung cancer. Although some therapies are effective in slowing down disease progression, they describe living in constant fear that the disease will eventually progress.
Lung cancer is often associated with a poor prognosis and patients describe that receiving a lung cancer diagnosis can feel like a “death sentence”. Many patients are diagnosed after the disease has progressed and are often left with limited treatment options. Patients and caregivers would like more treatment options available for advanced disease as well as a reimbursement criteria that allows their healthcare providers to have more flexibility when prescribing treatments.
Patients report that they have struggled with side effects related to some treatments. They reported that they had no symptoms from the actual cancer but struggled more with the side effects from treatment. Patients would like treatments with minimal side effects so that they can carry on with regular activities while on treatment. The importance of maintaining some quality of life cannot be overstated.
No patients within this evidence group submission had experience with the medication under review.
Not applicable.
Not applicable.
Reference
Canadian Cancer Statistics Advisory Committee in collaboration with the Canadian Cancer Society, Statistics Canada and the Public Health Agency of Canada. Canadian Cancer Statistics 2021. Toronto, ON: Canadian Cancer Society; 2021
To maintain the objectivity and credibility of the CADTH reimbursement review process, all participants in the drug review processes must disclose any real, potential, or perceived conflicts of interest. This Patient Group Conflict of Interest Declaration is required for participation. Declarations made do not negate or preclude the use of the patient group input. CADTH may contact your group with further questions, as needed.
Did you receive help from outside your patient group to complete this submission?
No.
Did you receive help from outside your patient group to collect or analyze data used in this submission?
No.
Financial Disclosures for Lung Health Foundation / The Ontario Lung Association.
Lung Cancer Canada (LCC) is a national charity with the purpose of increasing awareness about lung cancer, providing support and education to lung cancer patients and their families, to support research and to advocate for access to the best care for all lung cancer patients in all provinces and territories.
Through the LCC Medical Advisory Committee (MAC), we provide clinician input for submissions of new lung cancer drugs to the HTA process for many years. The LCC MAC consists of clinicians and key opinion leaders in the field of lung cancer across the countries.
The information provided in this submission is from publicly available sources, primarily published manuscripts and conference presentations, together with clinical experience of the members from the MAC. This submission is entirely independent of the manufacturer (Janssen).
Canadian NSCLC patients with an EGFR Exon 20 insertion are rare.
In 2022, lung cancer is again projected to be the leading cause of cancer deaths, accounting for 24.3% of cancer deaths.1 The projected number of new lung cancer cases in Canada in 2022 will be 30,000 (1); of these, approximately 88% will be diagnosed with non-small cell lung cancer (NSCLC).2,3
In Canada, approximately 15% of patients with NSCLC present with mutations in the epidermal-growth factor receptor (EGFR) gene.4 EGFR mutations include the common Exon 19 deletions and the L858R mutation, which make up 85 - 90% of the mutations we see. The remaining 10-15% of EGFR mutations consist of the rarer, uncommon mutations, which can be further subdivided into: “sensitizing” or “non-sensitizing”.
Sensitizing mutations, make up 90% of uncommon mutations, and are often compound, which means that they contain more than one EGFR mutation. Patients whose lung tumours contain sensitizing uncommon mutations can respond to the first and second-generation EGFR tyrosine kinase inhibitors (TKIs) currently used in clinical practice, including erlotinib and afatinib, and to third-generation EGFR TKI, osimertinib
Non-sensitizing mutations make up the remaining 10% of uncommon mutations, split between Exon 20 insertions and de novo T790M mutations. According to some estimates, patients with EGFR Exon 20 insertions make up between 0.1 – 4% of all NSCLC cases2,3, which means that there are few new patients diagnosed each year in Canada, approximately only 200-1000.
NSCLC patients with non-sensitizing uncommon mutations are resistant to the first and second-generation EGFR TKIs.5,6 One reason why EGFR TKIs do not work in patients with an EGFR Exon 20 insertion is because the small size of the binding pocket for the ATP Kinase interferes with the binding of the TKI. Efficacy data for third-generation EGFR TKI’s in patients EGFR Exon 20 insertions is still unknown and is being tested in clinical trials. These include trials with a double dose of osimertinib, a third generation EGFR TKI. While this trial is in a preliminary stage, the rationale for how the double dose will overcome the issue with the size of the binding pocket is unclear. In addition, several clinical trials are ongoing with poziotinib and mobocertinib. The results of these trials are not expected for some time.
The prognosis for patients with locally advanced or metastatic NSCLC EGFR Exon 20 insertions is poor, mostly because they have few treatment options and lack effective targeted therapies.
Several real-world studies, including one from Alberta7, have demonstrated that patients with EGFR Exon 20 insertions have much poorer outcomes in terms of median PFS (mPFS) and median overall survival (mOS) than patients with common EGFR mutations.5-7
Current treatments do not modify the underlying disease mechanisms. For patients with EGFR Exon 20 insertions, chemotherapy platinum doublet (CPD) is by default a standard of care and currently the only treatment used in the first line setting.8 The addition of immunotherapy to CPD makes little sense, as patients with EGFR mutations were excluded from the KEYNOTE189 trial because checkpoint inhibitors have not shown efficacy in the EGFR driver mutation.9
After patients progress on CPD, docetaxel may be used in the second line, however response rates are less than 10%..8
As mentioned previously, EGFR TKIs can be efficacious for patients whose tumours contain common EGFR mutations, but patients with EGFR Exon 20 insertions are resistant to EGFR TKIs and have low response to immunotherapy.10-14 However, as clinicians search for any treatment to help their patients, EGFR TKIs and immunotherapy are sometimes tried in desperation.
There is a significant unmet need for novel targeted therapies that will prolong PFS and improve health-related quality of life (HRQoL) for patients with EGFR Exon 20 insertions.
The ideal treatment for patients with an EGFR Exon 20 insertion is one that directly inhibits the driver mutation. The treatment should be well tolerated, with a predictable and low toxicity profile. The response should be durable and correlate with an improvement in quality of life. Oral medications are preferred over intravenous treatments.
Considering the treatment goals, please describe goals (needs) that are not being met by currently available treatments.
There is a significant unmet need for novel targeted therapies that will prolong PFS and improve health-related quality of life (HRQoL) for patients with EGFR Exon 20 insertions.
Currently available options:
How would the drug under review fit into the current treatment paradigm?
The current submission is for amivantamab in the second line setting for NSCLC patients with EGFR Exon 20 insertions, who have progressed on, or after CPD. This agrees with the indication and trial results of the CHRYSALIS-D study.18,19
CHRISALIS cohort D (CHRYSALIS-D) was a single-arm, open-label, Phase I/Ib dose escalation study (NCT02609776).(19) Patients with advanced NSCLC with EGFR Exon 20 insertions treated with amivantamab post CPD (n=81), experienced an overall response rate (ORR) of 43.2%, mPFS of 8.3 months and a mOS of 22.8 months with a median 14.5 month follow up, as determined by a blinded independent central review.19
Amivantamab is a bispecific monoclonal antibody that binds both to the extracellular domain of EGFR and to the extracellular domain of the MET receptor, blocking the binding of both EGF and MET ligands to their receptors.20
As we have learned from the literature and clinical practice, targeted therapies against driver mutations should ideally be offered in a first line setting for maximal efficacy. Clinical trials of amivantamab in NSCLC patients with Exon 20 insertion, in the first line setting, are ongoing.
Which patients would be best suited for treatment with the drug under review? Which patients would be least suitable for treatment with the drug under review?
The NSCLC patients most likely to respond to amivantamab are those with an EGFR Exon 20 insertion. Patients need to have an adequate performance status to be considered for this therapy.
Patients with EGFR Exon 20 insertions are identified using Next Generation Sequencing (NGS). NGS is routinely conducted in all patients with advanced NSCLC with a non-squamous and squamous histology, without a smoking history.
At this time, it is not yet possible to identify those specific patients who are most likely to respond to this therapy. As with all targeted therapies, studies will be conducted to identify potential biomarkers.
What outcomes are used to determine whether a patient is responding to treatment in clinical practice? How often should treatment response be assessed?
Amivantamab directly helps address the unmet treatment need in this uncommon patient population as it is a targeted agent that significantly improves response rates, progression-free survival, and overall survival compared to real-world controls, while improving aspects of a patient’s HRQoL.
The outcomes used in clinical practice are aligned with the outcomes typically used in clinical trials and include safety/side effect profiles, treatment response and clinical response which are evaluated at regular intervals. The intervals of evaluation in clinical practice are usually not as frequent as in clinical trials, where trial protocols need to be strictly adhered to. In general, patients in clinical practice are often seen and evaluated every 6-8 weeks with a variety of radiological imaging modalities, usually to evaluate baseline disease sites as well as a clinical evaluation to determine side effect profiles and general changes to HRQOL.
A clinically meaningful endpoint to treatment is a stable radiological response, especially if it is durable. In most patients, a radiological response to treatment is reflected by a clinical response, which is also durable.
The magnitude of response will vary across patients but should not vary across physicians.
HRQoL outcomes are often more subjective and are harder to evaluate. In the amivantamab trial, patient-reported outcome analyses show a modest initial improvement in overall symptom severity for cough and chest pain.21
Education of the drug side effect profile, for both physicians and patients, is beneficial for both and helps maintain patients on therapy to achieve the best results.
What factors should be considered when deciding to discontinue treatment with the drug under review?
Factors for consideration when deciding to discontinue amivantamab are similar to any other cancer therapy: disease progression and lack of clinical benefit.
In addition, adverse events may require patients to discontinue amivantamab temporarily or more permanently in some cases. In CHRYSALIS-D, treatment-emergent adverse events (TEAEs) leading to amivantamab discontinuation were reported for 11.8% patients treated, with 5.2% considered to be treatment-related.22
What settings are appropriate for treatment with [drug under review]? Is a specialist required to diagnose, treat, and monitor patients who might receive [drug under review]?
Ideally, this drug needs to be administered at a Cancer Centre or hospital, by personnel experienced in administering chemotherapy agents.
Amivantamab is an intravenous drug administered weekly for the first month (cycle) and then then every two weeks a month (cycle) until disease progression or unwanted toxicity.
Adverse reactions, particularly infusion reactions, can occur in the first week of the first cycle. In the amivantamab clinical trials, infusion reactions were very common, observed 63.4% of patients, with a median time to first onset of 47 minutes. The majority of infusion-related reactions were limited to the first infusion and were of Grade 1 (10.5%) or 2 (50.3%) severity.22 The discontinuation rate due to this side effect were low.
Infusion-related reactions can be prospectively managed by slow administration (delivering the dose over two days, 6 hours on day 1 and 4 hours on day 2) and by co-administering appropriate interventions including steroids and antihistamines.
As for all patients with advanced lung cancer, a medical oncology team is required to diagnose, treat and monitor patients.
In my clinical practice, this is doable.
None of my patients treated with amivantamab has yet experienced a grade three toxicity nor have they experienced an adverse event that have led to discontinuation. The pharmacy has developed a protocol, the nurses are experienced, and the patients well educated about the treatment and possible side effects. This has led to successful treatment delivery in our center.
Although the patients with EGFR Exon 20 insertions are very rare, we do encounter them in clinic. Similar to other EGFR mutated NSCLC patients, they are generally non-smokers. Patients with an EGFR Exon 20 insertion have few treatment options yet are desperate for treatment as most are young and have good performance status.
For these patients, none of the oral TKIs work. Immunotherapy, although not directly studied in this specific setting, is unlikely to work as well. As this population is so rare, adequately powered phase III clinical trials are unfeasible. This applies not only to oral TKIs and immunotherapy, but also to amivantamab. Additionally, this agent has been approved in the US, which reduces the potential participants for a phase III trial. With the incidence of EGFR Exon 20 insertion occurs in <4% of all newly diagnosed NSCLC patients, at least 30% of patients are too sick to even receive first-line CBD therapy, and about 50% of the remaining patients will get second-line therapy, <2% of patients will be candidates for amivantamab as second line therapy. Out of these potential patients, only about 50% will fulfill the stringent eligibility criteria to enroll into a study, making it impossible to generate overall survival or progression-free survival data through a phase III study within a reasonable timeframe. While waiting for the readout of a phase III study in this rare patient population, many patients would not receive the benefit of amivantamab.
Having the ability to identify the specific mutation, in this case an EGFR Exon 20 insertion, driving the tumour is good news, as it permits us to strategize on how to specifically inhibit that driver. Amivantamab is an exciting option for targeting this mutation. The ORR of 43.2% observed in the CHRYSALIS-D trial is exciting and encouraging. We are hopeful that this may become the new standard of care in this disease for second line treatment. Like other targeted therapies against driver mutations, we look forward to eventually offering this therapy to first line in the metastatic setting.
References
1. Brenner DR, Poirier A, Woods RR, Ellison LF, Billette JM, Demers AA, et al. Projected estimates of cancer in Canada in 2022. Cmaj. 2022;194(17):E601-e7.
2. Burnett H, Emich H, Carroll C, Stapleton N, Mahadevia P, Li T. Epidemiological and clinical burden of EGFR Exon 20 insertion in advanced non-small cell lung cancer: A systematic literature review. PLOS ONE. 2021;16(3):e0247620.
3. Riess JW, Gandara DR, Frampton GM, Madison R, Peled N, Bufill JA, et al. Diverse EGFR Exon 20 Insertions and Co-Occurring Molecular Alterations Identified by Comprehensive Genomic Profiling of NSCLC. J Thorac Oncol. 2018;13(10):1560-8.
4. Tan AC, Tan DSW. Targeted Therapies for Lung Cancer Patients With Oncogenic Driver Molecular Alterations. J Clin Oncol. 2022;40(6):611-25.
5. Girard N, Bazhenova L, Minchom A, Ignatius Ou S-H, Gadgeel SM, Trigo J, et al. WCLC Oral Presentation: Comparative clinical outcomes for patients with NSCLC harboring EGFR Exon 20 insertion mutations and common EGFR mutations. Oral Presentation 3390. 2020.
6. Girard N, Bazhenova L, Minchom A, Ou SI, Gadgeel SM, Trigo J, et al. MA04.07 Comparative Clinical Outcomes for Patients with NSCLC Harboring EGFR Exon 20 Insertion Mutations and Common EGFR Mutations. Journal Of Thoracic Oncology. 2021;16(3):S145-S6.
7. Janssen. Data on file. Health Outcomes and Healthcare Resource Utilization of Patients with Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutation Non-small Cell Lung Cancer (NSCLC) in Alberta. 2021.
8. Melosky B, Banerji S, Blais N, Chu Q, Juergens R, Leighl NB, et al. Canadian consensus: a new systemic treatment algorithm for advanced EGFR-mutated non-small-cell lung cancer. Curr Oncol. 2020;27(2):e146-e55.
9. Gadgeel S, Rodríguez-Abreu D, Speranza G, Esteban E, Felip E, Dómine M, et al. Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2020;38(14):1505-17.
10. Arcila ME, Nafa K, Chaft JE, Rekhtman N, Lau C, Reva BA, et al. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther. 2013;12(2):220-9.
11. Oxnard GR, Lo PC, Nishino M, Dahlberg SE, Lindeman NI, Butaney M, et al. Natural history and molecular characteristics of lung cancers harboring EGFR exon 20 insertions. J Thorac Oncol. 2013;8(2):179-84.
12. Naidoo J, Sima CS, Rodriguez K, Busby N, Nafa K, Ladanyi M, et al. Epidermal growth factor receptor exon 20 insertions in advanced lung adenocarcinomas: Clinical outcomes and response to erlotinib. Cancer. 2015;121(18):3212-20.
13. Vyse S, Huang PH. Targeting EGFR exon 20 insertion mutations in non-small cell lung cancer. Signal Transduction and Targeted Therapy. 2019;4(1):5.
14. Janssen. Data on file. ONCO CAPPS: EGFR Positive and EGFR Exon 20 Mutation Advanced Non-Squamous NSCLC. January 2022. 2022.
15. Gainor JF, Shaw AT, Sequist LV, Fu X, Azzoli CG, Piotrowska Z, et al. EGFR Mutations and ALK Rearrangements Are Associated with Low Response Rates to PD-1 Pathway Blockade in Non-Small Cell Lung Cancer: A Retrospective Analysis. Clin Cancer Res. 2016;22(18):4585-93.
16. Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer. New England Journal of Medicine. 2016;375(19):1823-33.
17. Sezer A, Kilickap S, Gümüş M, Bondarenko I, Özgüroğlu M, Gogishvili M, et al. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet. 2021;397(10274):592-604.
18. Janssen. Draft Product Monograph: Amivantamab. 2021.
19. Sabari JK, Shu CA, Park K, Leighl NB, Mitchell P, Kim S, et al. OA04.04 Amivantamab in Post-platinum EGFR Exon 20 Insertion Mutant Non-small Cell Lung Cancer. Journal of Thoracic Oncology. 2021;16(3):S108-S9.
20. Janssen. Phase 1B EDI1001 study protocol. 2019.
21. Janssen. CHRYSALIS PRO Analysis - Exon 20ins Expanded Efficacy Population (March 2021 CCO). 2021.
22. Janssen Research and Development. Data on file. Interim clinical study report for subjects with EGFR Exon 20 insertion mutationstreated with amivantamab monotherapy (30 March 2021 Cutoff). Protocol 61186372EDI1001; Phase 1 (CHRYSALIS). 2021.
To maintain the objectivity and credibility of the CADTH drug review programs, all participants in the drug review processes must disclose any real, potential, or perceived conflicts of interest. This conflict of interest declaration is required for participation. Declarations made do not negate or preclude the use of the clinician group input. CADTH may contact your group with further questions, as needed. Please see the Procedures for CADTH Drug Reimbursement Reviews (section 6.3) for further details.
Did you receive help from outside your clinician group to complete this submission?
No.
Did you receive help from outside your clinician group to collect or analyze any information used in this submission?
No.
List any companies or organizations that have provided your group with financial payment over the past two years AND who may have direct or indirect interest in the drug under review. Please note that this is required for each clinician who contributed to the input.
Name: Dr. Barbara Melosky
Position: Medical Oncologist, BC Cancer
Date: May 13, 2022
COI Declaration for Lung Cancer Canada Medical Advisory Committee — Clinician 1.
Name: Dr. Shaqil Kassam
Position: Medical Oncologist, Southlake Regional Hospital
Date: May 13 ,2022
COI Declaration for Lung Cancer Canada Medical Advisory Committee — Clinician 2.
Name: Dr. Ronald Burkes
Position: Medical Oncologist, Mount Sinai Health
Date: May 13, 2022
COI Declaration for Lung Cancer Canada Medical Advisory Committee — Clinician 3.
Name: Dr. Geoffrey Liu
Position: Medical Oncologist, Princess Margaret Cancer Centre
Date: May 13, 2022
COI Declaration for Lung Cancer Canada Medical Advisory Committee — Clinician 4.
Name: Dr Catherine Labbé
Position: Head of Respiratory Medicine Service, Université de Laval
Date: May 13, 2022
COI Declaration for Lung Cancer Canada Medical Advisory Committee — Clinician 5.
Name: Dr. Kevin Jao
Position: Medical Oncologist, Hôpital Sacré-Cœur, Montreal
Date: May 13, 2022
COI Declaration for Lung Cancer Canada Medical Advisory Committee — Clinician 6.
Name: Dr Nicole Bouchard
Position: Respirologist, Sherbrooke University Hospital
Date: May 13, 2022
COI Declaration for Lung Cancer Canada Medical Advisory Committee — Clinician 7.
Name: Dr. Quincy Chu
Position: Medical Oncologist, Cross Cancer Institute
Date: May 13, 2022
COI Declaration for Lung Cancer Canada Medical Advisory Committee — Clinician 8.
Name: Dr. Paul Wheatley-Price
Position: Medical Oncologist, The Ottawa Hospital; Associate Professor, Department of Medicine, University of Ottawa
Date: May 13, 2022
COI Declaration for Lung Cancer Canada Medical Advisory Committee — Clinician 9.
Name: Dr. Donna Maziak
Position: Thoracic Surgeon, The Ottawa Hospital
Date: May 13, 2022
COI Declaration for Lung Cancer Canada Medical Advisory Committee — Clinician 10.
Name: Dr. Rosalyn Juergens
Position: Chair, LCC Medical Advisory Committee; Medical Oncologist, Juravinski Cancer Center
Date: April 1, 2022
COI Declaration for Lung Cancer Canada Medical Advisory Committee — Clinician 11.
Name: Dr Normand Blais
Position: Medical Oncologist, Hôpital Notre Dame du CHUM
Date: May 13, 2022
COI Declaration for Lung Cancer Canada Medical Advisory Committee — Clinician 12.
Name: Dr. Lacey Pitre
Position: Medical Oncologist, Systemic Therapy Lead - Northeast Region, CCO/Ontario Health
Date: May 13, 2022
COI Declaration for Lung Cancer Canada Medical Advisory Committee — Clinician 13.
Name: Dr Jeffrey Rothenstein
Position: Medical Oncologist, Lakeridge Health
Date: May 13, 2022
COI Declaration for Lung Cancer Canada Medical Advisory Committee — Clinician 14.
Name: Dr. Callista Phillips
Position: Medical Oncologist, Hamilton Health Sciences Center
Date: May 13, 2022
COI Declaration for Lung Cancer Canada Medical Advisory Committee — Clinician 15.
Name: Dr Sunil Yadav
Position: Medical Oncologist, Saskatoon Cancer Centre
Date: May 13, 2022
COI Declaration for Lung Cancer Canada Medical Advisory Committee — Clinician 16.
Name: Dr. David Dawe
Position: Medical Oncologist, CancerCare Manitoba
Date: May 13, 20221
COI Declaration for Lung Cancer Canada Medical Advisory Committee — Clinician 17.
Name: Dr. Stephanie Snow
Position: President, Lung Cancer Canada; Medical Oncologist, The QEII Health Sciences Center
Date: May 13, 2022
COI Declaration for Lung Cancer Canada Medical Advisory Committee — Clinician 18.
Name: Dr. Parneet Cheema
Position: Medical Director, William Osler Health System
Date: May 13, 2022
COI Declaration for Lung Cancer Canada Medical Advisory Committee — Clinician 19.
Name: Dr. David Stewart
Position: Medical Oncologist, The Ottawa Hospital
Date: May 13, 2022
COI Declaration for Lung Cancer Canada Medical Advisory Committee — Clinician 20.
Name: Dr Randeep Sangha
Position: Associate Professor, University of Alberta; Medical Oncologist, Cross Cancer Institute
Date: May 13, 2022
COI Declaration for Lung Cancer Canada Medical Advisory Committee — Clinician 21.
OH-CCO’s Drug Advisory Committees provide timely evidence-based clinical and health system guidance on drug-related issues in support of CCO’s mandate, including the Provincial Drug Reimbursement Programs (PDRP) and the Systemic Treatment Program.
This input was jointly discussed at a DAC meeting.
The standard of care remains platinum-based chemotherapy. First-line platinum-based doublet chemotherapy +/- immunotherapy followed by docetaxel at the time of progression. In Ontario, most centers testing for this mutation is available.
Treatment goals would be tumor response, improvement in tumor related symptoms, quality of life, and prolonging life.
Considering the treatment goals in Section 3, please describe goals (needs) that are not being met by currently available treatments.
Not all patients respond to the current treatments available. There is a lack of established molecular therapies for this molecularly defined subgroup of lung cancer patients.
How would the drug under review fit into the current treatment paradigm?
Amivantamab would be used after all standard therapies acceptable to the patient have failed. Typically, this would be following platinum doublet chemotherapy and maintenance pemetrexed, although in some cases this would also be after docetaxel therapy.
Immune checkpoint inhibitors may also be used in these patients as combination first line therapy, or as second line therapy, as these patients were not explicitly tested for and excluded from pivotal trials, but it is expected that these drugs would be low efficacy and many patients and clinicians would forgo the toxicity of immunotherapy given the possibility of inferior efficacy.
Which patients would be best suited for treatment with the drug under review? Which patients would be least suitable for treatment with the drug under review?
Patients best suited would align with the study inclusion criteria (EGFR Exon 20 Insertion–Mutated NSCLC patients).
Patients least suited would align with the study exclusion criteria.
What outcomes are used to determine whether a patient is responding to treatment in clinical practice? How often should treatment response be assessed?
In clinical practice the outcome that is used to determine if a patient is responding to treatment is clinical improvement and radiologic improvement. Clinical assessed every 4 weeks and radiologic assessment every 3 months.
What factors should be considered when deciding to discontinue treatment with the drug under review?
Treatment continued until unequivocal disease progression or loss of clinical benefit, unacceptable toxicity, withdrawal of consent.
What settings are appropriate for treatment with [drug under review]? Is a specialist required to diagnose, treat, and monitor patients who might receive [drug under review]?
A specialist is required in an infusion clinic or a hospital (outpatient) setting.
Not applicable.
To maintain the objectivity and credibility of the CADTH drug review programs, all participants in the drug review processes must disclose any real, potential, or perceived conflicts of interest. This conflict of interest declaration is required for participation. Declarations made do not negate or preclude the use of the clinician group input. CADTH may contact your group with further questions, as needed. Please refer to the Procedures for CADTH Drug Reimbursement Reviews (section 6.3) for further details.
Did you receive help from outside your clinician group to complete this submission? If yes, please detail the help and who provided it.
Ontario Health provided secretariat support to the DAC.
Did you receive help from outside your clinician group to collect or analyze any information used in this submission? If yes, please detail the help and who provided it.
No.
List any companies or organizations that have provided your group with financial payment over the past two years AND who may have direct or indirect interest in the drug under review. Please note that this is required for each clinician who contributed to the input.
Name: Dr. Donna Maziak
Position: Ontario Health Lung Cancer Drug Advisory Committee Lead
Date: 13/05/2022
COI Declaration for OH-CCO Lung Cancer Drug Advisory Committee — Clinician 1.
Name: Dr. Peter Ellis
Position: Ontario Health Lung Cancer Drug Advisory Committee Member
Date: 13/05/2022
COI Declaration for OH-CCO Lung Cancer Drug Advisory Committee — Clinician 2.
Name: Dr. Andrew Robinson
Position: Ontario Health Lung Cancer Drug Advisory Committee Member
Date: 13/05/2022
COI Declaration for OH-CCO Lung Cancer Drug Advisory Committee — Clinician 3.
Name: Dr. Stephanie Brule
Position: Ontario Health Lung Cancer Drug Advisory Committee Member
Date: 13/05/2022
COI Declaration for OH-CCO Lung Cancer Drug Advisory Committee — Clinician 4.
Name: Dr. Sara Kuruvilla
Position: Ontario Health Lung Cancer Drug Advisory Committee Member
Date: 13/05/2022
COI Declaration for OH-CCO Lung Cancer Drug Advisory Committee — Clinician 5.
Copyright © 2023 - Canadian Agency for Drugs and Technologies in Health. Except where otherwise noted, this work is distributed under the terms of a Creative Commons Attribution-NonCommercial- NoDerivatives 4.0 International licence (CC BY-NC-ND).
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