Abstract 322P
Background
Patients with endocrine-sensitive HR+/HER2‒ ABC had improved OS with palbociclib (PAL)+fulvestrant (FUL) vs. placebo (PBO)+FUL (Turner NEJM 2018;20:1926). Subgroup analyses suggested that prior chemotherapy (CT) for ABC may be associated with decreased OS benefit of PAL+FUL vs. PBO+FUL. We examined baseline characteristics of patients from PALOMA-3 with and without prior CT for ABC and evaluated prognostic factors for OS.
Methods
In total, 521 patients who had progressed on prior endocrine therapy (ET) were randomized 2:1 to PAL (125 mg; schedule 3/1)+FUL (500 mg) or PBO+FUL; 34% received prior CT. A multivariate analysis adjusting for baseline factors evaluated prognostic factors for OS. Median OS was estimated by the Kaplan-Meier method (data cutoff Apr 13, 2018). A Cox proportional hazards model was used to calculate HRs and CIs.
Results
Endocrine sensitivity, nonvisceral disease, Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0, and no prior CT in any setting were prognostic factors for OS (Table). In patients without prior CT in any setting and in ABC, PAL+FUL had longer median OS vs. PBO+FUL (46.2 vs. 29.7 mo; HR, 0.68 [95% CI: 0.41‒1.15] and 39.7 vs. 29.5 mo; HR, 0.75 [95% CI: 0.56‒1.01], respectively). In patients with prior CT in ABC, median OS was similar (25.6 vs. 26.2 mo; HR, 0.91 [95% CI: 0.63‒1.32]). Patients who had not received CT in the ABC setting had fewer prior lines of treatment in any setting and in the ABC setting vs. patients with prior CT in ABC (≤2 prior systemic therapies: 69% vs. 42%; ≤1 prior lines of therapy for ABC: 82% vs. 33%, respectively). Table: 322P
| HR* | 95% CI | |
| PAL+FUL vs. PBO+FUL | 0.807 | 0.638−1.021 |
| Sensitivity to prior hormonal therapy (yes vs. no) | 0.588 | 0.453−0.764 |
| Disease site (nonvisceral vs. visceral) | 0.541 | 0.426−0.688 |
| Prior CT (yes vs. no) | 1.450 | 1.102−1.907 |
| Baseline ECOG PS (≥1 vs. 0) | 1.470 | 1.171−1.846 |
*HR <1 indicates a lower hazard in the first category of the variable; HR >1 indicates a higher hazard in the first category of the variable.
Conclusions
Prognostic factors for OS included endocrine sensitivity, nonvisceral disease, ECOG PS of 0, and no prior CT. Together with previous findings, exploratory analyses suggest PAL+FUL prolonged OS in patients without prior CT for ABC, with fewer prior regimens, and with ET sensitivity vs. PBO+FUL.
Clinical trial identification
NCT01942135.
Editorial acknowledgement
Editorial support was provided by Anny Wu, PharmD, of ICON plc (North Wales, PA, USA) and was funded by Pfizer Inc.
Legal entity responsible for the study
Pfizer Inc.
Funding
Pfizer Inc.
Disclosure
H.S. Rugo: Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): Merck; Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): OBI Pharma; Research grant/Funding (institution): Odonate; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Daiichi; Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (institution): Seattle Genetics; Travel/Accommodation/Expenses: Mylan; Advisory/Consultancy: Puma; Advisory/Consultancy: Samsung. M. Cristofanilli: Honoraria (self), Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy, Research grant/Funding (institution): G1 Therapeutics; Advisory/Consultancy: CytoDyn; Advisory/Consultancy: Sermonix; Advisory/Consultancy: Foundation Medicine. S. Loibl: Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Teva; Research grant/Funding (institution): Vifor. N. Harbeck: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche. A. DeMichele: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Menarini Biosystems; Research grant/Funding (institution): Calithera; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Genentech; Advisory/Consultancy: Context Therapeutics. H. Iwata: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Chugai; Advisory/Consultancy, Research grant/Funding (self): Daiichi-Sankyo; Research grant/Funding (self): Pfizer; Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self), Research grant/Funding (self): Novartis; Research grant/Funding (self): Eli Lilly; Honoraria (self): Eisai. Y.H. Park: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Eisai; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Roche. A. Brufsky: Advisory/Consultancy: Pfizer. K. Puyana Theall: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer. X. Huang: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer. L. McRoy: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer. E. Bananis: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer. N.C. Turner: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Novartis.