Clinical outcomes in patients (pts) with estrogen receptor–positive (ER+)/human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC) with objective response (OR) or without objective response (non-OR) in PALOMA-2

Background: 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). Methods: 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. Results: 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%). Conclusions: 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: 332PClinical benefit in patients with or without confirmedOR in PALOMA-2ORNon-ORPAL+LETPBO+LETPAL+LETPBO+LETAll pts, n19477250145mPFS (95% CI), mo37.227.416.58.2(28.1–NE)(22.0–31.1)(12.8–22.2)(5.6–11.0)HR (95% CI)0.65 (0.46–0.92)0.55 (0.43–0.70)mDOR (95% CI), mo27.720.9––(24.7–36.1)(16.5–27.6)Pts with MD, n1947614495mPFS (95% CI), mo37.227.410.95.6(28.1–NE)(22.2–31.1)(8.2–11.2)(5.3–8.3)HR (95% CI)0.66 (0.47–0.94)0.72 (0.54–0.97)HR=hazard ratio; NE=not estimable. Open table in a new tab HR=hazard ratio; NE=not estimable. Clinical trial identification: NCT01740427. Editorial acknowledgement: 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. Legal entity responsible for the study: Pfizer Inc. Funding: Pfizer Inc. Disclosure: 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.

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