Palbociclib plus fulvestrant as second- or later-line therapy for patients with locally advanced, inoperable or metastatic HR+/HER2-breast cancer in Germany: Interim results of the INGE-B phase II study

Abstract Background In the PALOMA-3 trial, palbociclib plus fulvestrant demonstrated a clinically meaningful improvement in overall survival compared with fulvestrant plus placebo in patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer who had relapsed or progressed on prior endocrine therapy (Turner NC et al., NEJM 2018). Detailed analyses for first-line (1L) and second- or later- line (2L+) therapy are still limited. Methods The prospective, multicenter phase 2 INGE-B trial was designed to generate efficacy and safety data on the combination of palbociclib with letrozole (1L) or fulvestrant (1L, 2L+) in accordance with the PALOMA trials and to generate so far lacking trial data on the combination of palbociclib with anastrozole (1L), exemestane (1L) or letrozole (2L+). This pre-planned interim analysis was conducted to evaluate data on pts receiving palbociclib plus fulvestrant as 1L or 2L+ therapy. The primary endpoint was the clinical benefit rate (CBR) in pts with measurable disease according to RECIST v1.1. Key secondary endpoints included the overall response rate (ORR), the CBR for all pts, and safety. Data were analyzed with descriptive statistics. Results At the cut-off date of the interim analysis (Dec 17, 2018), 124 pts have been recruited from 03/2017 through 06/2018 at 47 sites across Germany to receive palbociclib plus fulvestrant (1L: 57 pts; 2L+: 67 pts). 57 of 67 pts treated in 2L+ were evaluable. Median age was 68.0 years, 91.2% (n = 52) of pts had an ECOG performance score of 0 or 1. 28.1% (n = 16) of pts presented with non-measurable bone-only disease. The CBR was 35% (n = 14) for the 40 pts with measurable disease (RECIST v1.1) and 51% (n = 29) for all pts (investigator assessment). The ORRs were 25% (n = 10) and 21% (n = 12), respectively. Grade 3/4 adverse events experienced by at least 10% of pts were neutropenia (n = 21, 36.8%) and leukopenia (n = 7, 12.3%). Conclusions This INGE-B interim analysis showed a remarkable clinical benefit for palbociclib plus fulvestrant as second- or later-line therapy for pts with HR+/HER2- advanced breast cancer. No new safety signals were detected. Clinical trial identification 2015-001603-32. Legal entity responsible for the study iOMEDICO AG. Funding Pfizer Pharma GmbH. Disclosure D. Luftner: Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Celgene; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Teva; Advisory / Consultancy: Tesaro; Advisory / Consultancy: L’Oreal; Advisory / Consultancy: MSD; Advisory / Consultancy: AstraZeneca. M.K. Welslau: Honoraria (self), Advisory / Consultancy: Amgen; Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: GILEAD; Honoraria (self), Advisory / Consultancy: HEXAL; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Medac; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self): Astellas; Honoraria (self): AstraZeneca. A. Welt: Advisory / Consultancy: Roche; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Eisai; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Amgen. M. Zaiss: Advisory / Consultancy: Roche; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Celgene; Advisory / Consultancy: Janssen; Advisory / Consultancy: Novartis. N.W. Marschner: Leadership role, Shareholder / Stockholder / Stock options: iOMEDICO AG; Research grant / Funding (institution): Pfizer. All other authors have declared no conflicts of interest.