Abstract 309P
Background
BYLieve (NCT03056755) confirmed efficacy and safety of ALP + FUL for HR+, HER2−, PIK3CA-mut ABC in the post-CDK4/6 inhibitor (CDKi) setting. Further analyses were performed to compare efficacy results from BYLieve with standard treatment in the real-world setting.
Methods
Pts who progressed on CDKi + aromatase inhibitor (AI) and were treated with ALP + FUL in BYLieve were compared to pts from the de-identified Flatiron Health-Foundation Medicine Clinico-Genomics Database (CGDB) who had similar baseline covariates. Two real-world cohorts were retrieved from CGDB based on post-CDKi treatment in the real-world setting: first cohort excluded pts with HER2+ drugs, clinical study drug, or alpelisib, and second cohort excluded pts with drugs from first cohort or chemotherapy. Primary and secondary endpoints were to evaluate and compare progression-free survival and proportion of pts remaining progression free at 6 mo after the index date (date of the start of the next line of therapy), respectively, with ALP + FUL in BYLieve vs. CGDB real-world cohorts. Weighting by odds, propensity score matching, and exact matching were performed separately for each endpoint.
Results
855 pts with PIK3CA mut and prior CDKi + hormone therapy were identified from CGDB; further matching to 120 pts from BYLieve identified 95 pts without HER2+ drugs, clinical study drug, or alpelisib and 65 pts from CGDB without these drugs or chemotherapy. In unadjusted results and in 3 methods to weight/match pts, primary and secondary endpoints consistently favored treatment with ALP + FUL in BYLieve over standard treatments in either real-world cohort. Table: 309P
Progression-free survival (PFS) pre and post weighting/matching
| Method | Median PFS, mo (95% CI) [real-world PFS for CGDB] | PFS at 6 mo, % | ||||||
| BYLieve: ALP + FUL | CGDB: Standard treatment | BYLieve: ALP + FUL | CGDB: Standard treatment, excluding chemo | BYLieve: ALP + FUL | CGDB: Standard treatment | BYLieve: ALP + FUL | CGDB: Standard treatment, excluding chemo | |
| Unadjusted | 7.3 (5.6-8.3) | 3.6 (3.1-6.1) | 7.3 (5.6-8.3) | 3.4 (2.9-3.9) | 54.6 | 40.5 | 54.6 | 32.9 |
| Weighting by odds | 7.3 (5.6-8.3) | 3.7 (3.1-6.1) | 7.3 (5.6-8.3) | 3.4 (2.8-5.1) | 54.6 | 40.1 | 54.6 | 28.8 |
| Propensity score | 8.0 (5.6-8.6) | 3.5 (3.0-5.4) | 7.0 (5.3-8.6) | 3.4 (2.8-3.7) | 58.7 | 37.4 | 54.6 | 29.9 |
| Exact | 6.5 (5.3-8.3) | 3.4 (2.9-3.9) | 6.0 (5.1-8.3) | 3.4 (2.8-3.8) | 54.4 | 34.4 | 52.4 | 29.3 |
Conclusions
Comparing data from BYLieve with the real-world setting further supports the clinical benefit of ALP + FUL for treatment of HR+, HER2−, PIK3CA-mut ABC post-CDKi treatment.
Clinical trial identification
Editorial acknowledgement
Medical editorial assistance was provided by Rob M. Camp of Healthcare Consultancy Group, LLC, and funded by Novartis Pharmaceuticals Corporation.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
S. Turner: Full/Part-time employment: Novartis. S.K.L. Chia: Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self): Eli Lilly; Honoraria (self), Research grant/Funding (institution): Hoffman LaRoche; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Genomic Health. H. Kanakamedala: Advisory/Consultancy, Research grant/Funding (institution): Novartis. W-C. Hsu: Advisory/Consultancy, Research grant/Funding (institution): Novartis. J. Park: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. D. Chandiwana: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. A. Ridolfi: Full/Part-time employment: Novartis. C-L. Yu: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. J.P. Zarate: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis; Spouse/Financial dependant: Johnson & Johnson. H.S. Rugo: Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (institution): Merck; Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): OBI Pharma; Research grant/Funding (institution): Odonate Therapeutics; Research grant/Funding (institution), Travel/Accommodation/Expenses: Daiichi-Sankyo; Research grant/Funding (institution): Eisai; Research grant/Funding (institution), Travel/Accommodation/Expenses: Macrogenics; Travel/Accommodation/Expenses: Mylan; Research grant/Funding (institution): Immunomedics; Advisory/Consultancy: Samsung; Advisory/Consultancy: Celtrion; Travel/Accommodation/Expenses: AstraZeneca.