|
| Status |
Public on Mar 18, 2022 |
| Title |
HTG mRNA expression for Progessive versus Stable disease in breast cancer RADICAL trial patients |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Background: AZD4547 is a potent and selective inhibitor of FGFR-1, 2 and 3 receptor tyrosine kinases. Phase 1 studies both in Europe and Japan have shown that the compound is well tolerated and shows activity in patients with solid tumours. Here, we hypothesised that AZD4547 could reverse resistance to AIs such as anastrozole and letrozole. Methods: After a safety run-in study in which 6 patients had PK and safety assessments on combined AI plus AZD4547, we recruited 52 eligible patients with metastatic breast cancer who had progressed on treatment with anastrozole or letrozole. The primary objective of the phase lla study was to assess the efficacy of AZD4547 based on the change in tumour size when used in combination with either anastrozole or letrozole in ER positive breast cancer patients who have progressed on treatment with either anastrozole or letrozole in any setting. Results:. According to centrally reviewed RECIST criteria, five partial response (PR) and 8 stable disease (SD) patients were observed from a total of 50 assessable cases, giving a Clinical Benefit Rate (PR + SD) of 26% (95% CI: 14.6-40.3%). RNA-Seq was done on a subset of patients’ samples: 6 differentially-expressed-genes could distinguish those who benefited from the addition of AZD4547. Eleven patients had retinal pigment epithelial detachments (RPEDs) either in one or both eyes which was asymptomatic and reversible, although RPED recurred in one patient on re-treatment. Twenty six (50%) and 7(13%) patients had elevated phosphate and calcium, respectively. Conclusions: in a group of unselected ER positive women with aromatase inhibitor-resistant metastatic breast cancer, FGFR pathway inhibition combined with letrozole or anastrozole provided clinical benefit in a significant proportion of patients with manageable toxicity.
|
| |
|
| Overall design |
Relative expression of mRNA was assessed on FFPE samples using the HTG EdgeSeq Oncology Biomarker Panel.
|
| |
|
| Contributor(s) |
Pardo OE, Coombes RC, Seckl MJ |
| Citation(s) |
35301407, 35688802 |
| |
| Submission date |
Mar 15, 2022 |
| Last update date |
Jun 27, 2022 |
| Contact name |
Olivier Emmanuel Pardo |
| E-mail(s) |
o.pardo@imperial.ac.uk
|
| Phone |
02085942814
|
| Organization name |
Imperial College
|
| Department |
Surgery and Cancer
|
| Street address |
Hammersmith Hospital, Du Cane Road
|
| City |
London |
| ZIP/Postal code |
W12 0NN |
| Country |
United Kingdom |
| |
|
| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (22)
|
|
| Relations |
| BioProject |
PRJNA816334 |
Less...
More...