Presidential Symposium 1 Proffered Paper session

LBA2_PR - 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

Presentation Number
LBA2_PR
Lecture Time
17:00 - 17:15
Speakers
  • Massimo Cristofanilli (Chicago, US)
Location
Hall A2 - Room 18, ICM München, Munich, Germany
Date
20.10.2018
Time
16:30 - 18:20

Abstract

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.

Table. OS in the ITT Population and by Subgroup
Subgroup n (%) HR (95% CI) PAL+FUL
median OS (95% CI)
PBO+FUL
median OS (95% CI)
1-sided
P value
Interaction
P value
ITT, stratified 521 (100) 0.81 (0.64–1.03) 34.9 (28.8–40.0) 28.0 (23.6–34.6) 0.043
ITT, unstratified 521 (100) 0.79 (0.63–1.00) 34.9 (28.8–40.0) 28.0 (23.6–34.6) 0.025
Sensitivity to previous endocrine therapy
Endocrine sensitive 410 (78.7) 0.72 (0.55–0.94) 39.7 (34.8–45.7) 29.7 (23.8­–37.9) 0.124
Endocrine resistant 111 (21.3) 1.14 (0.71–1.84) 20.2 (17.2–26.4) 26.2 (17.5–31.8)
Site of metastatic disease
Visceral disease 311 (59.7) 0.85 (0.64–1.13) 27.6 (24.4–31.2) 24.7 (20.8–31.8) 0.442
Nonvisceral disease 210 (40.3) 0.69 (0.46–1.04) 46.9 (39.3–NE) 35.4 (24.6–NE)
Menopausal status at study entry
Postmenopausal 413 (79.3) 0.73 (0.57–0.95) 34.8 (28.8–40.1) 27.1 (22.8–32.1) 0.251
Pre/perimenopausal 108 (20.7) 1.07 (0.61–1.86) 38.0 (24.4–NE) 38.0 (22.2–NE)
FUL=fulvestrant; HR=hazard ratio; ITT=intent-to-treat; NE=not estimable; OS=overall survival; PAL=palbociclib; PBO=placebo.

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.

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