There is no preferred next-line treatment (tx) for patients (pts) with HR+/HER2− advanced breast cancer post-progression on a CDK4/6 inhibitor (CDK4/6i; except alpelisib for PIK3CA mutations). This pooled exploratory analysis of the MONALEESA (ML) studies examined outcomes of various tx strategies post-progression on RIB+ET.
Data from pts receiving 1L therapy in ML-2, -3, and -7 were pooled and pts receiving 1st subsequent (2L) therapies were analyzed. Three groups of 2L therapies were assessed: ET only, CT ± any other therapy, and targeted therapy (CDK4/6i, mTORi, PI3Ki, AKTi, etc ± ET). 2L CT & targeted therapy groups were mutually exclusive. Median durations of 1L and 2L tx, and OS were analyzed by KM methods. Weighted Cox regressions were performed using inverse probability tx weighting to ensure compatible pt baseline characteristics between tx arms.
Median follow-up time was 74 mo. 461 pts treated with RIB (81%) and 440 (86%) with PBO discontinued study tx and received a 2L tx. In the RIB arms, the most common 2L therapies were ET only (40%), CT (29%), combined with targeted therapy (28%), and other (4%); for the PBO arms, 34% received CT as a 2L therapy and 31% each received ET only or combined with targeted therapy (5% received other). In 14% and 20% of pts in the RIB and PBO arms, the 2L therapy was a CDK4/6i; of these, 31% and 12% were RIB. In general, the duration of both 1L and 2L therapy was longer for pts treated with RIB vs PBO (Table). In both arms, pts who received 2L CT had the shortest study tx duration; those who received 2L targeted therapy combination had the longest. Among pts on 1L RIB+ET, 2L CDK4/6i use was associated with the longest mOS (84 [84-NE] mo), followed by ET only (60 [51-68] mo), then a non-CDK4/6i targeted therapy (52 [43-72] mo); 2L CT was associated with the shortest mOS (37 [32-48] mo).
In general, the duration of any 2L therapy was numerically longer post-1L RIB+ET vs PBO+ET, and 2L CT was used less frequently for pts on 1L RIB vs PBO. Both findings confirm that upfront tx with RIB does not worsen pt outcomes. The trend toward improved outcomes of 2L therapies after 1L RIB suggests a post-tx effect that merits further exploration.
Kevin Kalinsky,1 Erika Hamilton,2 Laura Spring,3 Peter A. Fasching,4 Sandra Franco,5 Richard De Boer,6 Javier Cortes,7 Dejan Juric,3 Aditya Bardia,3 Sina Haftchenary,8 Agnes Lteif,9 Juan Pablo Zarate,9 Liyi Cen,9 Patrick Neven10
1Winship Cancer Institute at Emory University, Atlanta, GA.
2Breast and Gynecologic Cancer Research Program, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN.
3Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA.
4University Hospital Erlangen, Comprehensive Cancer Center Erlangen–European Metropolitan Region of Nuremberg and Department of Gynecology and Obstetrics, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
5Medical Director Luis Carlos Sarmiento Angulo Cancer Treatment and Research Center CTIC, Bogotá DC, Colombia.
6Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia.
7International Breast Cancer Center, Grupo Quiron, Madrid and Barcelona, Spain.
8Novartis Pharmaceuticals Canada, Montreal, QC, Canada.
9Novartis Pharmaceuticals Corporation, East Hanover, NJ.
10Multidisciplinary Breast Centre, Universitair Ziekenhuis Leuven, Leuven, Belgium.