Abstract 330P
Background
CDK4/6 inhibitors (CDK4/6i) + endocrine therapy (ET) are recommended for 1L HR+/HER2− ABC. To date, only MONALEESA (ML)-3 (postmenopausal) and ML-7 (premenopausal), which included/ constituted 1L patients (pts), have reported a significant improvement in OS. Other pivotal 1L studies include PALOMA (P)-2, MONARCH-3 and ML-2, for which OS data are still not mature. The randomized phase II P-1 trial reported OS in 1L postmenopausal pts. Regarding choice of ET partner, the PARSIFAL trial recently found no difference in outcomes with 1L CDK4/6i + FUL or LET. Therefore, an MAIC was performed with ML-3 and P-1 to understand potential differences in survival outcomes in these 1L populations.
Methods
This was an unanchored MAIC of PFS and OS with RIB+FUL vs. PAL+LET using individual pt data from ML-3 and aggregated data from P-1. To match pts in P-1, pts in ML-3 were limited to those with no prior ET for ABC and no (neo)adjuvant LET ≤ 12 mo before enrollment. Pts in both arms of ML-3 were re-weighted to match average baseline characteristics of pts in corresponding arms of P-1. Matching adequacy was assessed by standardized mean differences (SMDs). PFS and OS were compared in pts receiving RIB+FUL vs. PAL+LET using KM estimators and Cox regressions.
Results
329 and 178 pts from RIB+FUL and PBO+FUL arms of ML-3 were matched to 84 and 81 pts from PAL+LET and PBO+LET arms of P-1. After weighting (effective sample size 221.4 for RIB), pts were well balanced on all characteristics (SMD < 1%). Results (ref: PAL+LET) are shown in the table. Table: 330P
| Outcome | RIB+FUL Weighted | Median (95%CI), mo | HR (95%CI) | P | |
| RIB+FUL | PAL+LET | ||||
| PFS | N | 27.1 (22.1, 33.6) | 20.0 (13.8, 27.7) | 0.839 (0.595, 1.184) | .3185 |
| Y | 27.8 (23.8, 35.8) | 0.784 (0.551, 1.117) | .1777 | ||
| OS | N | Not reached | 37.5 (28.4, not reached) | 0.587 (0.388, 0.888) | .0116 |
| Y | Not reached | 0.513 (0.328, 0.801) | .0033 |
Conclusions
Using an MAIC to adjust for trial differences revealed PFS and OS results favoring 1L RIB+ FUL vs. PAL+LET in postmenopausal pts with HR+/HER2− ABC, and demonstrated a significant benefit for OS. The results inform treatment decisions and support the use of 1L RIB+FUL in this pt population.
Clinical trial identification
Editorial acknowledgement
Medical writing support was provided by Chris Carter, PhD, at MediTech Media, Ltd, funded by Novartis Pharmaceuticals Corporation.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
P.A. Fasching: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Research Grant; Advisory Board/Consultancy: Novartis; Research grant/Funding (institution), Research Grant: BionTech; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Roche; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Celgene; Honoraria (self), Speaker Bureau/Expert testimony, Speaker Bureau: Daiichi-Sankyo; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory Board/Consultancy; Speaker Bureau: Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Macrogenics; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Puma; Research grant/Funding (institution), Research Grant: Cepheid; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory Board/Consultancy; Speaker Bureau: Eli Lilly; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: AstraZeneca. T. Delea: Research grant/Funding (institution), Research Grant: Novartis. Y-S. Lu: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Research Grant; Advisory Board/Consultancy; Speaker Bureau: Novartis; Honoraria (self), Advisory/Consultancy, Research Grant: Pfizer; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Boehringer Ingelheim; Research grant/Funding (institution), Research Grant: Roche; Research grant/Funding (institution), Research Grant: Merck Sharp and Dohme; Research grant/Funding (institution), Research Grant: Pfizer; Honoraria (self), Speaker Bureau/Expert testimony, Speaker Bureau: Eisai. R. DeBoer: Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Roche; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Genomic Health. S.A. Hurvitz: Research grant/Funding (institution), Research Grant: Ambryx; Research grant/Funding (institution), Research Grant: Amgen; Research grant/Funding (institution), Research Grant: Bayer; Research grant/Funding (institution), Travel/Accommodation/Expenses, Research Grant; Travel Support: OBI Pharma; Research grant/Funding (institution), Research Grant: Bimarin; Research grant/Funding (institution), Research Grant: Cascadian; Research grant/Funding (institution), Research Grant: Daiichi Sankyo; Research grant/Funding (institution), Research Grant: Dignitana; Research grant/Funding (institution), Research Grant: Genentech; Research grant/Funding (institution), Research Grant: Glaxo-Smith Kline; Research grant/Funding (institution), Travel/Accommodation/Expenses, Research Grant; Travel Support: Eli Lilly; Research grant/Funding (institution), Research Grant: Macrogenics; Research grant/Funding (institution), Research Grant: Medivation; Research grant/Funding (institution), Research Grant: Merrimack; Research grant/Funding (institution), Travel/Accommodation/Expenses, Research Grant; Travel Support: Novartis; Research grant/Funding (institution), Research Grant: Pfizer; Research grant/Funding (institution), Research Grant: Pieris; Research grant/Funding (institution), Research Grant: Puma; Research grant/Funding (institution), Research Grant: Roche; Research grant/Funding (institution), Research Grant: Seattle Genetics. A. Moynahan: Research grant/Funding (institution), Research Funding: Novartis. D. Chandiwana: Shareholder/Stockholder/Stock options, Full/Part-time employment, Employment and Stock Ownership: Novartis. B. Lanoue: Shareholder/Stockholder/Stock options, Full/Part-time employment, Employment and Stock Ownership: Novartis. H. Hu: Shareholder/Stockholder/Stock options, Full/Part-time employment, Employment and Stock Ownership: Novartis. A. Thuerigen: Shareholder/Stockholder/Stock options, Full/Part-time employment, Employment and Stock Ownership: Novartis. J. O'Shaughnessy: Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Merck; Honoraria (self), Advisory/Consultancy, Advisory Board/Consultancy: Seattle Genetics.