5410 - Overall survival (OS) with palbociclib plus fulvestrant in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2_) advanced breast cancer (ABC): Analyses from PALOMA-3

Background

Endocrine therapy (ET)–resistant ABC is dependent on cyclin dependent kinase (CDK) 4/6. In the prospective, randomized, double-blind, phase 3 PALOMA-3 study, the CDK4/6 inhibitor PAL in combination with FUL significantly improved progression-free survival (PFS) vs placebo (PBO)+FUL (median PFS, 11.2 vs 4.6 mo; absolute difference, 6.6 mo; hazard ratio [HR] 0.50 [95% CI, 0.40–0.62]; P<0.000001). Here, we report OS analysis with a median follow up of 44.8 mo.

Methods

HR+/HER2– ABC (N=521) patients (pts) who had relapsed or progressed on prior ET were randomized 2:1 to PAL (125 mg/d orally, schedule 3/1) + FUL (500 mg per standard of care) or PBO+FUL. Primary endpoint was investigator-assessed PFS. A key secondary endpoint was OS. OS analysis occurred when approximately 60% (n≈310) of the 521 pts died.

Results

Median OS improved with PAL+FUL vs PBO+FUL by an absolute difference of 6.9 mo (Table). In pts with sensitivity to prior ET, the absolute improvement in median OS was 10.0 mo with PAL+FUL vs PBO+FUL. In pts without visceral disease, median OS significantly improved with PAL+FUL vs PBO+FUL (11.5 mo). Time to end of the next-line treatment was 18.8 (PAL+FUL) and 14.1 (PBO+FUL) mo (HR 0.68 [95% CI, 0.56–0.84]; P<0.0001). Improvements in median OS, although not statistically significant at the prespecified level, were shown with PAL+FUL vs PBO+FUL regardless of ESR1 mutation status or prior lines of therapy. Median time on subsequent therapy was similar in both arms; median time to chemotherapy was 17.5 (PAL+FUL) and 8.8 (PBO+FUL) mo (HR 0.58; P<0.000001). No new safety signals were observed with longer follow-up.

Conclusions

In HR+/HER2– ABC pts, PAL+FUL showed a clinically meaningful improvement in OS (6.9 mo vs PBO+FUL), especially in pts with sensitivity to prior ET. The absolute difference of PFS gain was maintained in OS.

Funding: Pfizer (NCT01942135)

Clinical trial identification

(NCT01942135)

Editorial Acknowledgement

Editorial support was provided by Jennifer Fetting, PhD, and Kevin O’Regan, PhD, of Complete Healthcare Communications, LLC (North Wales, PA), a CHC Group company, and funded by Pfizer Inc.