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

Cancer Med. 2020 Jul;9(14):4929-4940. doi: 10.1002/cam4.3091. Epub 2020 May 18.

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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Female
  • Humans
  • Japan
  • Letrozole / pharmacology
  • Letrozole / therapeutic use*
  • Middle Aged
  • Piperazines / pharmacology
  • Piperazines / therapeutic use*
  • Pyridines / pharmacology
  • Pyridines / therapeutic use*

Substances

  • Antineoplastic Agents
  • Piperazines
  • Pyridines
  • Letrozole
  • palbociclib

Associated data

  • ClinicalTrials.gov/NCT01684215