PALOMA-3 Trial Shows Benefits to Overall Survival as Measured by Prognostic Indicators

Analysis from the PALOMA-3 clinical trial showed that the combination of palbociclib and fulvestrant improved overall survival in patients with hormone receptor–positive, HER2-negative advanced breast cancer.

In the poster session, Hope S. Rugo, MD, FASCO, Director, Breast Oncology and Clinical Trials Education, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, presented an analysis of PALOMA-3, looking at prognostic factors for overall survival in patients with hormone receptor–positive, HER2-negative advanced breast cancer.

Previously published phase 3 data from the PALOMA-2 and PALOMA-3 clinical trials supported the use of palbociclib plus endocrine therapy as a standard of care for patients with hormone receptor–positive, HER2-negative advanced breast cancer.¹ When compared with placebo plus fulvestrant, palbociclib plus fulvestrant showed improved overall survival in patients with endocrine-sensitive, hormone receptor–positive, HER2-negative advanced breast cancer.² Previous chemotherapy treatment for patients with advanced breast cancer may be associated with a decreased overall surival benefit of palbociclib plus fulvestrant compared with placebo plus fulvestrant, based on subgroup analyses.

In this study, Dr Rugo and colleagues looked at baseline characteristics of patients from PALOMA-3 with and without previous chemotherapy for advanced breast cancer to determine if there were overall survival prognostic factors.

Patients (N = 521) who had progressed on previous endocrine therapy were randomized at a 2:1 ratio to receive palbociclib 125 mg plus fulvestrant 500 mg or placebo plus fulvestrant. Previous chemotherapy had been administered to 34% of these patients.

The study showed that prognostic factors for overall survival were endocrine sensitivity, nonvisceral disease, Eastern Cooperative Oncology Group performance status of 0, and no previous chemotherapy in any setting. Patients lacking previous chemotherapy in any setting and in advanced breast cancer, who received palbociclib plus fulvestrant had longer median overall survival when compared with those treated with placebo plus fulvestrant (46.2 vs 29.7 months: hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.41-1.15; and 39.7 vs 29.5 months: HR, 0.75; 95% CI, 0.56-1.01, respectively).

Interestingly, for patients who had received previous chemotherapy, median overall survival was similar (25.6 vs 26.2 months: HR, 0.91; 95% CI, 0.63-1.32). However, patients who had not received chemotherapy in the advanced breast cancer setting had fewer previous lines of treatment in any setting and in the advanced breast cancer setting when compared with patients with previous chemotherapy treatment for advanced breast cancer (≤2 previous systemic therapies: 69% vs 42%; ≤1 previous lines of therapy for advanced breast cancer: 82% vs 33%, respectively).

Building on previous findings, these analyses strongly suggest that the palbociclib plus fulvestrant combination improves overall survival in patients who had not received previous chemotherapy for advanced breast cancer, with fewer previous regimens, and with endocrine therapy sensitivity.

Source: Rugo HS, Cristofanilli M, Loibl S, et al. Prognostic factors for OS in patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer (HR+/HER2− ABC): analyses from PALOMA-3. Ann Oncol. 2020;31(4_suppl). Abstract 322P.

References
1. Finn RS, Cristofanilli M, Ettl J, et al. Treatment effect of palbociclib plus endocrine therapy by prognostic and intrinsic subtype and biomarker analysis in patients with bone-only disease: a joint analysis of PALOMA-2 and PALOMA-3 clinical trials. Breast Cancer Res Treat. 2020;184:22-35.
2. Turner NC, Slamon DJ, Ro J, et al. Overall survival with palbociclib and fulvestrant in advanced breast cancer. N Engl J Med. 2018;379:1926-1936.