Background

The efficacy and tolerability of palbociclib (P) + endocrine therapy (ET) in ABC patients (pts) was previously established; here, we report results in the Asia-Pacific (AP) region (Australia, Japan, Korea, Taiwan).

Methods

In PALOMA-2, postmenopausal women untreated for their HR+/HER2- ABC were randomized 2:1 to P (125 mg/d [3/1 schedule]) + letrozole (L; 2.5 mg/d) or placebo (PB)+L. In PALOMA-3, women of any menopausal status with HR+/HER2- ABC, whose disease had progressed after previous ET, were randomized 2:1 to P + fulvestrant (F; 500 mg) or PB+F.

Results

Of 666 PALOMA-2 pts, 92 (14%) were from the AP region (P+L, 64; PB+L, 28). Baseline characteristics: median age (61 y) younger than overall population; white (20%), Asian (79%); ≥2 disease sites (70%); visceral disease (59%); prior (neo)adjuvant ET (64%); disease-free interval >12 months since prior (neo)adjuvant therapy (58%). Median PFS (mPFS): 22 mo (95% CI, 19-26) for P+L vs 14 mo (7-22) for PB+L (HR, 0.49; 1-sided P=0.007). All-grade treatment-emergent adverse events (TEAEs) (P+L/PB+L) occurred in 100%/96% of pts; the most common AE in the P+L arm was neutropenia (91%). 55% of P+L pts required a dose reduction due to AEs. Of 521 PALOMA-3 pts, 114 (22%) were from the AP region (P+F, 78; PB+F, 36). Baseline characteristics: younger (median age 53 y) and more premenopausal pts (38%) vs overall population; white (23%), Asian (75%); ≥2 disease sites (66%); visceral disease (57%); prior ET (100%); prior chemotherapy for ABC (70%). mPFS: 13 mo (95% CI, 9-16) for P+F vs 6 (4-9) for PB+F (HR, 0.51; 1-sided P=0.002). All-grade TEAEs (P+F/PB+F) occurred in 100%/92% of pts; the most common AE in the P+F arm was neutropenia (95%). 51% of P+F pts required a dose reduction due to AEs.

Conclusions

Because PALOMA-2 only enrolled postmenopausal pts and percentages of premenopausal pts in AP vs other regions was higher, the proportion of AP pts was higher in PALOMA-3 vs -2. P+ET showed clinically meaningful improvement in mPFS vs PB+ET and a tolerable safety profile in AP pts with HR+/HER2- ABC in the 1^st-line and later-lines of therapy, regardless of menopausal status.

Clinical trial identification

Pfizer (NCT01740427; NCT01942135).

Legal entity responsible for the study

Pfizer Inc

Funding

Pfizer Inc.

Disclosure

S-A. Im: Consulting or advisory role for AstraZeneca, Novartis, Hanmi Corp, and Spectrum, N. Masuda: Honoraria from Chugai and AstraZeneca, K. Inoue: Research funding from Pfizer, Lilly, Chugai, Daiichi-Sankyo, Taiho, MSD, Parexel (Puma), S-B. Kim: Research funding from Novartis, Sanofi-Aventis, Kyowa-Kirin Inc, and Dongkook Pharma Co., Ltd. A. Redfern: Advisory board for Pfizer Australia, J. Lombard: Honoraria from Roche and AstraZeneca, D. Lu, K. Puyana Theall, E.G. Gauthier: Employee and owns stock in Pfizer, H. Mukai: Honoraria from AstraZeneca, Eisai, Novartis Pharma and Taiho Pharmaceutical, and received research funds from Chugai Pharmaceutical, Nippon Kayaku, Novartis Pharma, Pfizer Japan, and Sanofi

All other authors have declared no conflicts of interest.