PALOMA-2 confirmed the efficacy and safety of P+L vs placebo (PBO)+L in pts with treatment-naive ER+/HER2– ABC (Finn NEJM, 2016). Here, we report efficacy and safety among P+L-treated pts in 2 subgroups of either exposed or not exposed to prior neo(adjuvant) endocrine therapy (ET) and/or chemotherapy (CT).
Postmenopausal women (N = 666) were randomized 2:1 to receive P (125 mg QD; 3 wk on, 1 wk off) + L (2.5 mg QD; continuously) or PBO+L. Prior neo(adjuvant) ET/CT with curative intent was allowed; prior ET or CT for recurrent advanced or metastatic disease was not. The primary endpoint was investigator-assessed progression-free survival (PFS); other key endpoints included response rates and safety. Exposure to P among subgroups is also presented.
At baseline, 249/444 pts (56%) in the P+L arm had received prior ET and 213 (48%) had received prior CT (Table). Pts previously treated were slightly younger vs those not previously treated. Exposure to P+L was similar across subgroups. In P+L-treated pts, median PFS was 22.2/25.7 mo with prior ET/no prior ET and 22.4/25.7 mo for prior CT/no prior CT. The significant clinical benefit of P+L vs PBO+L remained regardless of prior ET/CT exposure. Across all subgroups, the incidence of all-causality adverse events (AEs) was similar; neutropenia was the most frequent AE. AEs leading to permanent discontinuation occurred in
Regardless of prior (neo)adjuvant treatment, P+L significantly prolonged PFS vs PBO+L and demonstrated consistent efficacy in pre-treated and non–pre-treated subgroups of postmenopausal pts with ER+/HER2– ABC. Tolerability was similar across subgroups and consistent with the known safety profile of P.
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R.S. Finn: Honoraria: Bayer, Pfizer, Bristol-Myers Squibb, Novartis, Eisai; Consulting or advisory role: Pfizer, Bayer, Novartis, Bristol-Myers Squibb, Merck; Research funding Pfizer. K.A. Gelmon: Consulting or advisory role: Pfizer, Novartis, AstraZeneca, NanoString Technologies, Merck. J. Ettl: Honoraria: Pfizer, Novartis, Roche; Consulting or advisory role: Pfizer, Novartis Pharma KK; Speakers’ bureau: Pfizer, Novartis, Roche, Celgene. J. Asselah: Consulting or advisory role: Pfizer, Novartis. A. Castrellon: Research funding: Novartis; Consulting or advisory role: Biotheranostics. A. Ruiz Simón: Honoraria: Pfizer, Novartis, Roche. A.A. Joy: Consulting or advisory role: Pfizer, Novartis, Roche, Eli Lilly, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingleheim. D. Lu, E.R. Gauthier, A. Mori: Pfizer employee and shareholder. H.S. Rugo: Speakers’ bureau and honoraria: Genomic health; Research funding (Plexxikon Macrogenics, OBI Pharma, Eisai, Pfizer, Novartis, Eli Lilly, GlaxoSmithKline, Genentech, Celsion, Merck, Clovis Oncology. V. Diéras: Consulting and advisory role: Genentech, Lilly, Pfizer, AbbVie, Novartis Pharma KK, Roche-Peru; Speakers’ bureau: Pfizer, Novartis Pharma KK, Roche-Peru.