The San Antonio Breast Cancer Symposium (SABCS) 2020 –one of the most relevant meetings providing up-to-the-minute information on breast cancer research– was held online from Tuesday, December 8 through Friday, December 11. MEDSIR was amongst the attendees of this four-day meeting which virtually united thousands of academics, private researchers and physicians from across the Globe to accelerate progress against breast cancer amid the COVID-19 pandemic.
Dr Antonio Llombart-Cussac, Head of Medical Oncology Service at Hospital Arnau de Vilanova (Valencia, Spain), presented results from the MEDSIR sponsored clinical trial BIOPER (NCT03184090).
BIOPER is a multicenter, open-label, non-controlled phase II trial for patients with hormone receptor positive (HR[+]) and human epidermal growth factor receptor 2 negative (HER2[-]) metastatic breast cancer (MBC), who had previously received endocrine therapy (ET) combined with palbociclib (P) and achieved clinical benefit to that treatment before experiencing disease progression. A total of 33 patients were recruited from 21 centers throughout Italy and Spain.
The trial had two main objectives: i) To assess the clinical benefit of continuing the treatment with P in combination with a different ET in the study population; ii) To investigate a molecular profile that could help identifying the subset of patients that obtain more clinical benefit from continuing on P after progression on a prior P-containing regimen. The analysis of protein markers included studying the expression of Retinoblastoma (Rb), phospho-Rb, and targets of the Rb family including Cyclin D1, Cyclin E1 and Cyclin-dependent Kinases 4 and 6 (CDK4, CDK6) in 30 available tissue biopsies that were collected at baseline.
Results presented at SABCS 2020 showed the BIOPER study met its primary clinical objective, reaching a clinical benefit rate (CBR) of 34.4% in the study population. For the clinical secondary objectives, overall response rate (ORR) and duration of response (DoR) were also evaluated. ORR was 6.3%, and among responders mean DoR was 17 months. Median progression-free survival (PFS) and overall survival (OS) were also evaluated and were 2.6 and 23.9 months respectively.
The study also met its primary biological objective in the biomarker evaluable set (N=21), with 19% patients presenting loss of Rb protein expression, which has been described as a driver of resistance to CDK4/6 inhibitors. The correlation analysis of protein marker expression with PFS showed that PFS was significantly worst in patients whose tumors overexpressed Cyclin D1 and Cyclin E1 and had a higher pRb/ Rb ratio. These preliminary molecular analyses are consistent with previous studies showing a correlation between Cyclin E1 overexpression and tumor resistance to treatment with P+ET, preventing benefit from P treatment rechallenge beyond progression.
The safety profile was in line with that reported in previous studies too. The incidence of grade 3 or 4 AEs was 48.5%, the most common of which were neutropenia and leukopenia. There were no discontinuations due to AEs nor treatment-related deaths.
The BIOPER study results might help physicians decide on the best treatment options for breast cancer patients that stop responding to initial Palbociclib-based therapy, while contributing to personalizing patients’ treatment according to their specific biological characteristics. Further research is now ongoing to characterize this promising strategy and the evolution of genetic mechanisms of resistance to P+ET in an international randomized phase II study sponsored by MEDSIR, the PALMIRA clinical trial (NCT03809988).
You can find our poster about the BIOPER trial here.
MEDSIR is a company fully dedicated to helping clinical oncological investigators from all over the world turn their scientific ideas into strategic, fully designed, fully funded investigator-initiated clinical trials. If you would like to know more about us or about this clinical trial or other MEDSIR-sponsored studies, do not hesitate to contact and join us.