Combination cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) + endocrine therapy is the recommended first-line (1L) tx for HR+/HER2− ABC. A statistically significant overall survival (OS) benefit with ribociclib (RIB)+AI was reported for MONALEESA-2 (ML-2); final OS data for the MONARCH 3 (MON-3) trial of abemaciclib (ABE)+AI are pending. QoL is an important endpoint that affects tx decisions. MAIC analysis allows for comparative effectiveness in the absence of head-to-head trial data. Here, patient (pt)- reported QoL for ML-2 (RIB+AI) and MON-3 (ABE+AI) were compared using MAIC with a focus on individual domains; the PALOMA-2 trial could not be considered because of the different pt-reported outcome measures evaluated in the trial compared to ML-2 and MON-3.
An anchored MAIC of QoL with RIB+AI vs ABE+AI was performed using data from EORTC QLQ-C30 and BR-23 questionnaires, individual pt data from ML-2 (data cutoff: 6/10/2021), and published data from MON-3 (data cutoff, 11/3/2017). All available QoL data were used in this analysis; the median follow-up for ML-2 was 79.7 months, and the median duration of follow-up at which QoL data were reported for MON-3 was 26.73 months. Inclusion and exclusion criteria were generally similar. Pts in both arms of ML-2 were weighted to match baseline characteristics in the corresponding arms of MON-3. Cox proportional hazards model was used to generate hazard ratios (HRs); anchored HRs were calculated using the Bucher method. Time to sustained deterioration (TTSD) was calculated as the time from randomization to a ≥ 10-point deterioration, with no later improvement above this threshold.
205 and 149 pts from the RIB/PBO arms of ML-2 were matched to 328 and 165 pts from the ABE/PBO arms of MON-3. After weighting, pt characteristics were well balanced. TTSD significantly favored RIB vs ABE in appetite loss (HR, 0.46; 95% CI, 0.27-0.81), diarrhea (HR, 0.42; 95% CI, 0.23-0.79), and fatigue (HR, 0.63; 95% CI, 0.41-0.96), as measured by QLQ-C30 and arm symptoms (HR, 0.49; 95% CI, 0.30-0.79), as assessed by BR-23. TTSD did not significantly favor ABE vs RIB in any functional or symptom scale of the QLQ-C30 or BR-23.
This MAIC suggests that RIB+AI is associated with better symptom-related QoL vs ABE+AI for postmenopausal pts with HR+/HER2− ABC in the 1L setting. QoL differences between CDK4/6i and their associated adverse event profiles may impact clinical decisions in HR+/HER2− ABC.
Hope S. Rugo,1 Joyce O’Shaughnessy,2 Komal Jhaveri,3 Sara M. Tolaney,4 Fatima Cardoso,5 Aditya Bardia,6 Purnima Pathak,7 Sina Haftchenary,8 Peter A. Fasching9
1University of California San Francisco Comprehensive Cancer Center, San Francisco, CA.
2Texas Oncology-Baylor University Medical Center and The US Oncology Research Network, Dallas, TX.
3Memorial Sloan Kettering Cancer Center, New York, NY.
4Dana-Farber Cancer Institute, Boston, MA.
5Breast Unit, Champalimaud Clinical Centre, Champalimaud Foundation, Lisbon, Portugal.
6Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA.
7Novartis Pharmaceuticals Corporation, East Hanover, NJ.
8Novartis Pharmaceuticals Canada, Montreal, QC, Canada.
9University Hospital Erlangen, Comprehensive Cancer Center Erlangen–European Metropolitan Region of Nuremberg, and Department of Gynecology and Obstetrics, Friedrich- Alexander University Erlangen-Nuremberg, Erlangen, Germany.