Palbociclib-letrozole as first-line treatment for advanced breast cancer: Updated results from a Japanese phase 2 study

Abstract

Palbociclib is a highly selective, reversible, oral inhibitor of cyclin-dependent kinases 4 and 6 that is approved to treat hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer. An open-label, single-arm, Japanese phase 2 study was conducted to investigate the efficacy and safety of palbociclib plus letrozole as first-line treatment in 42 postmenopausal patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer. The probability of progression-free survival originally reported at 1 year was 75.0% (90% confidence interval, 61.3-84.4), but median progression-free survival was not attained at the primary analysis. In this report, updated efficacy and safety results with a longer follow-up period are presented. The median duration of treatment in the updated analysis was 33.0 months (range, 1.8-49.2). The probability of progression-free survival at 1 year was 75.6% (90% confidence interval, 62.4-84.7). Median progression-free survival was 35.7 months (95% confidence interval, 21.7-46.7). Objective response rate and disease control rate were 47.6% (95% confidence interval, 32.0-63.6) and 85.7% (95% confidence interval, 71.5-94.6), respectively. Common treatment-related adverse events (all grades; grade 3/4) were neutropenia (100%; 93%), leukopenia (83%; 60%), and stomatitis (76%; 0%). Treatment-related febrile neutropenia was reported in one patient. In general, no clinically meaningful deterioration in health-related quality of life was observed. Palbociclib plus letrozole remained effective and tolerable in Japanese postmenopausal patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in this updated analysis.

Trial registration: ClinicalTrials.gov NCT01684215.

Keywords: Japanese; advanced breast cancer; cyclin-dependent kinase; letrozole; palbociclib.

Conflict of interest statement

Authors SH and YU are employees of Pfizer R&D Japan. YU also owns stock in Pfizer Inc. YM is an employee of Pfizer Japan Inc. HI received honoraria from Chugai, Daiichi‐Sankyo, AstraZeneca, and Pfizer; manuscript fees from Eisai; and research funding from MSD, Chugai, Daiichi‐Sankyo, and Boehringer Ingelheim. KI’s institution received research funding from Parexel, Puma Biotechnology, Pfizer, Novartis, MSD, GSK, Chugai, and Daiichi‐Sankyo. NM received honoraria from Chugai, Pfizer, Eli Lilly, Eisai, Takeda, and AstraZeneca; is a board member of the Japan Breast Cancer Research Group Association; and his institution received research funding from Chugai, AstraZeneca, Kyowa‐Kirin, MSD, Novartis, Pfizer, Eli Lilly, Eisai, and Daiichi‐Sankyo. SO received honoraria from Chugai, AstraZeneca, Eisai, Pfizer, Taiho, Kyowa‐Kirin, Nippon Kayaku, and Novartis, and research funding from Taiho and Eisai. RN received honoraria from Pfizer, Novartis, and Chugai. MTa received honoraria from Pfizer, AstraZeneca, Eli Lilly, and Eisai; and research funding from Taiho, Kyowa‐Kirin, and Eisai. MTo received honoraria from AstraZeneca and Eli Lilly; research funding from Taiho, Kyowa‐Kirin, Shimadzu, AFF Technology, Bizcom Japan, C&C Research Laboratories, Astellas, AstraZeneca, and Chugai; scholarship endowments from Chugai, Eisai, and Pfizer; and is a member of the board (no salary) of the Japan Breast Cancer Research Group association, Kyoto Breast Cancer Research Network, and Organisation for Oncology and Translational Research.

© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Figures

Figure 1

Kaplan‐Meier estimated PFS probability in the full analysis set. CI, confidence interval; PFS, progression‐free survival

Figure 2

Kaplan‐Meier estimated PFS probability by patient subgroup. A, Visceral and nonvisceral metastasis subgroups. B, DFI since prior (neo)adjuvant therapy subgroups. C, Prior and no prior endocrine therapy subgroups. D, Prior and no prior chemotherapy subgroups. E, Age

Figure 3

Kaplan‐Meier estimated PFS probability for patients with and without dose reduction during the first 90 d. Patients with PFS time within 90 d were excluded. CI, confidence interval; NE, not estimable; PFS, progression‐free survival

Figure 4

Kaplan‐Meier estimated OS probability in the full analysis set. CI, confidence interval; NE, not estimable; NR, not reached; OS, overall survival

Figure 5

CONSORT diagram of subsequent therapy. aOne patient continued commercially available letrozole only. AE, adverse event

Figure 6

Time course of subsequent therapies in each patient. *Patients who were being treated with commercially available palbociclib plus letrozole or letrozole alone at the data cutoff date. OS, overall survival

Figure 7

Change from baseline in patient‐reported HRQoL scale scores. A, FACT‐B total score. B, TOI total score. Bars indicate standard deviations. FACT‐B, Functional Assessment of Cancer Therapy‐Breast; HRQoL, health‐related quality of life; TOI, Trial Outcome Index

Figure 8

Kaplan‐Meier estimated TTD probability in FACT‐B score. CI, confidence interval; FACT‐B, Functional Assessment of Cancer Therapy‐Breast; TTD, time to definitive deterioration