Overall survival (OS) with palbociclib (PAL) + fulvestrant (FUL) in women with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC): Updated analyses from PALOMA-3.

Massimo Cristofanilli Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Feinberg School of Medicine, Chicago, IL info_outline Massimo Cristofanilli, Hope S. Rugo, Seock-Ah Im, Dennis J. Slamon, Nadia Harbeck, Igor Bondarenko, Norikazu Masuda, Marco Colleoni, Angela DeMichele, Sherene Loi, Hiroji Iwata, Ben O'Leary, Eustratios Bananis, Yuan Liu, Xin Huang, Sindy Kim, Mariajose Lechuga, Nicholas C. Turner

Authors Massimo Cristofanilli Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Feinberg School of Medicine, Chicago, IL info_outline Massimo Cristofanilli, Hope S. Rugo, Seock-Ah Im, Dennis J. Slamon, Nadia Harbeck, Igor Bondarenko, Norikazu Masuda, Marco Colleoni, Angela DeMichele, Sherene Loi, Hiroji Iwata, Ben O'Leary, Eustratios Bananis, Yuan Liu, Xin Huang, Sindy Kim, Mariajose Lechuga, Nicholas C. Turner Organizations Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Feinberg School of Medicine, Chicago, IL, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea, David Geffen School of Medicine, University of California Los Angeles, Santa Monica, CA, Brustzentrum der Universität München (LMU), Munich, Germany, Dnipropetrovsk Medical Academy, City Multiple-Discipline Clinical Hospital #4, Dnipropetrovsk, Ukraine, National Hospital Organization, Osaka National Hospital, Osaka, Japan, European Institute of Oncology, Milan, Italy, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC, Australia, Aichi Cancer Center Hospital, Nagoya, Japan, Royal Marsden Hospital and Institute of Cancer Research, London, United Kingdom, Pfizer Inc, New York, NY, Pfizer Inc, San Diego, CA Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Pfizer Inc Background: In PALOMA-3, a randomized, double-blind, placebo-controlled, phase 3 study, PAL+FUL significantly prolonged progression-free survival (PFS) compared with placebo (PBO) + FUL (1-sided P <0.0001). The final protocol-specified OS analysis, which was conducted with a median follow-up of 44.8 months (mo), showed improved OS with PAL+FUL vs PBO+FUL (median OS, 34.9 vs 28.0 mo; hazard ratio, 0.814 [95% CI, 0.644–1.029]; 1-sided P =0.0429). Here, we report the results from an OS analysis with a longer median follow-up of 73.3 mo. Methods: A total of 521 patients (pts) with HR+/HER2– ABC who had progressed on prior endocrine therapy were randomized 2:1 to PAL (125 mg/d orally, 3/1 week schedule) + FUL (500 mg intramuscular injection) or PBO+FUL. Investigator-assessed PFS was the primary endpoint; OS was a key secondary endpoint. An ad hoc OS analysis was performed when 393 events (75% of the total population) were observed. Circulating tumor DNA (ctDNA) analysis was conducted among pts who consented for this study. Results: Improvement in OS continues to be observed with longer follow-up, with a hazard ratio of 0.806 (95% CI, 0.654–0.994; 1-sided nominal P =0.0221). The 5-year OS rate was 23.3% (95% CI, 18.7–28.2) with PAL+FUL and 16.8% (95% CI, 11.2–23.3) with PBO+FUL. Favorable OS with PAL+FUL vs PBO+FUL was observed in most subgroups except among pts who were endocrine resistant or had prior chemotherapy for ABC. No new safety signals were identified. Eighteen pts remain on study treatment, including 15 (4.3%) on PAL+FUL and 3 (1.7%) on PBO+FUL. A post-study cyclin-dependent kinase 4/6 inhibitor was received by 20 pts (7.5%) in the PAL+FUL arm and 32 pts (22.2%) in the PBO+FUL arm. ctDNA analyses of tumor mutation profiles (ie, ESR1 , PIK3CA , RB1 ) at the end of treatment and their effect on OS will also be presented. Conclusions: The clinically meaningful improvement in OS with PAL+FUL was maintained with >6 years of median follow-up in pts with HR+/HER2– ABC who had progressed on prior endocrine treatment. Pfizer (NCT01942135) Clinical trial information: NCT01942135 . Updated OS in the ITT population and by subgroup. Subgroup n (%) Hazard Ratio (95% CI) PAL+FUL median OS (95% CI) PBO+FUL median OS (95% CI) 1-sided P value ITT population 521 (100) 0.81 (0.65–0.99) 34.8 (28.8–39.9) 28.0 (23.5–33.8) 0.0221 Sensitivity to prior endocrine therapy Yes 410 (78.7) 0.76 (0.60–0.96) 39.7 (34.4–45.7) 29.5 (23.5–36.3) 0.011 No 111 (21.3) 0.97 (0.62–1.5) 19.9 (17.4–26.4) 26.2 (17.5–31.8) 0.440 Prior chemotherapy in ABC Yes 177 (34.0) 0.97 (0.69-1.4) 24.6 (21.3-30.0) 24.3 (18.9-36.3) 0.432 No 344 (66.0) 0.72 (0.55-0.94) 39.3 (34.5-44.4) 29.7 (23.8-35.5) 0.008 ITT=intent-to-treat.