In the phase 3 PALOMA-2 trial, palbociclib (PAL) + letrozole (LET) significantly improved progression-free survival (PFS) vs placebo (PBO) + LET in pts with ER+/HER2– ABC. We investigated clinical outcomes of pts who achieved a confirmed OR compared with those who did not (data cutoff date: 31 May 2017).
Postmenopausal pts untreated for ER+/HER2- ABC were randomized 2:1 to PAL (125 mg/d [Schedule 3/1]) + LET (2.5 mg/d) or PBO+LET. Median PFS (mPFS), median duration of OR (mDOR), baseline characteristics, safety, and PAL exposure were compared in pts with or without OR by treatment arm.
The PAL+LET and PBO+LET groups comprised 444 and 222 pts, respectively; 338 and 171 pts had measurable disease (MD) at baseline. Baseline characteristics were similar in OR and non-OR pts. OR was achieved by 194 (overall, 44%; MD, 57%) and 77 (35%; 45%) pts in the PAL and PBO arms, respectively. Of the pts who achieved OR in the PAL arm, 49% occurred within the first 3 months, 75% within 6 months, and 90% within 1 year. In the PAL arm, more OR than non-OR pts had visceral disease (62% vs 38%), de novo metastatic disease (50% vs 28%), and no prior hormonal therapy (55% vs 35%); fewer OR than non-OR pts had a disease-free interval of ≤ 12 months (14% vs 28%). mPFS was significantly prolonged with PAL+LET vs PBO+LET in both OR and non-OR pts (overall and with MD; Table); in OR pts, mDOR was longer with PAL+LET vs PBO+LET. Safety profiles were similar and independent of response; neutropenia was the most common all-grade AE in the PAL arm (OR, 86%; non-OR, 78%) and rates of PAL dose reduction due to AEs were similar (41%; 38%).
PAL+LET provided significant clinical benefit vs PBO+LET in both OR and non-OR pts; the safety profile was similar to previously reported results in the overall population. PAL is an effective treatment regardless of OR. Pfizer (NCT01740427)Table: 332P
Clinical benefit in patients with or without confirmed OR in PALOMA-2
|All pts, n||194||77||250||145|
|mPFS (95% CI), mo||37.2||27.4||16.5||8.2|
|HR (95% CI)||0.65 (0.46–0.92)||0.55 (0.43–0.70)|
|mDOR (95% CI), mo||27.7||20.9||–||–|
|Pts with MD, n||194||76||144||95|
|mPFS (95% CI), mo||37.2||27.4||10.9||5.6|
|HR (95% CI)||0.66 (0.47–0.94)||0.72 (0.54–0.97)|
HR=hazard ratio; NE=not estimable.
Clinical trial identification
Legal entity responsible for the study
Editorial support was provided by Jennifer Fetting, PhD, and Kevin O’Regan, PhD, of Complete Healthcare Communications, LLC (West Chester, PA), a CHC Group company, and funded by Pfizer Inc.
H.S. Rugo: Research funding: Plexxikon, Macrogenics, OBI Pharma, Eisai, Pfizer, Novartis, Eli Lilly, Genentech, Merck; Travel support: Mylan, Puma Biotechnology Merck, Pfizer, Amgen. 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. A.A. Joy: Consulting or advisory role: Pfizer, Novartis, Roche, Eli Lilly, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Abbvie. N. Harbeck: Honoraria: Lilly, Novartis, Pfizer. A. Castrellon: Consulting or advisory role: Myriad, Biotheranostics; Research funding: Pfizer, Puma Biotechnology, Novartis, Cascadian Therapeutics. H. Mukai: Honoraria: AstraZeneca, Eisai, Novartis Pharma, Taiho Pharmaceutical; Research funds: Chugai Pharmaceutical, Nippon Kayaku, Novartis Pharma, Pfizer Japan, Sanofi. J.M. Walshe: Honoraria: Genomic Health, Roche. A. Mori, E. Gauthier, D.R. Lu, E. Bananis: Employee and shareholder: Pfizer M. Martín: Honoraria: AstraZeneca, Roche, Novartis, PharmaMar, Celgene, Eli Lilly; Research funds: Roche, Novartis. V. Dieras: Consulting and advisory role: Genentech, Lilly, Pfizer, AbbVie, Novartis Pharma KK, Roche-Peru; Speakers bureau: Pfizer, Novartis Pharma KK, Roche-Peru. All other authors have declared no conflicts of interest.