Palbociclib with Fulvestrant or Letrozole in Endocrine-Sensitive Patients with HR-Positive/HER2-Negative Advanced Breast Cancer: A Detailed Safety Analysis of the Randomized PARSIFAL Trial

Oncologist. 2023 Jan 18;28(1):23-32. doi: 10.1093/oncolo/oyac205.

Abstract

Background: Palbociclib has gained a central role in the treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). Despite its manageable toxicity profile, venous thromboembolism (VTE) or interstitial lung disease (ILD)/pneumonitis may infrequently occur. Therefore, we provide a comprehensive summary of the safety and tolerability of the combination of endocrine therapy and palbociclib among patients included in the randomized phase 2 PARSIFAL study.

Materials and methods: Patients with endocrine-sensitive HR+/HER2- ABC and no prior therapy in an advanced setting (n = 486) were randomly assigned 1:1 to receive fulvestrant-palbociclib (FP) or letrozole-palbociclib (LP). Laboratory tests and the incidence of adverse events (AEs) were recorded at baseline and day 1 of each cycle. Progression-free survival (PFS) was estimated for patients with and without VTE.

Results: A total of 483 patients were analyzed. Neutropenia, leukopenia, anemia, asthenia, arthralgia, fatigue, and diarrhea were the most frequent AEs in both groups. Febrile neutropenia occurred in 3 (1.2%) patients of the FP group and in 1 (0.4%) patient in the LP group. Six (2.5%; 0.4% grade 3) patients in the FP group and 6 patients (2.5%; 0.4% grade 3) in the LP group experienced ILD/pneumonitis. Pulmonary embolism was reported in 12 (5.0%) patients in the FP group and 6 (2.5%) patients in the LP group. Advanced age at baseline was the only factor significantly associated with an increased risk of pulmonary embolism (P < .01).

Conclusion: The PARSIFAL data confirmed the favorable safety profile of both palbociclib regimens. VTE and ILD/pneumonitis were occasionally reported, and their early detection allowed patients to continue treatment effectively without detriment to efficacy.

Clinicaltrials.gov identifier: NCT02491983; https://clinicaltrials.gov/ct2/show/NCT02491983).

Keywords: advanced breast cancer; endocrine therapy; interstitial lung disease; neutropenia; palbociclib; pneumonitis; venous thromboembolism.

Publication types

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

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms*
  • Female
  • Fulvestrant / therapeutic use
  • Humans
  • Letrozole / therapeutic use
  • Pulmonary Embolism* / etiology
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Venous Thromboembolism* / etiology

Substances

  • Fulvestrant
  • Letrozole
  • palbociclib
  • Receptor, ErbB-2
  • Receptors, Estrogen

Associated data

  • ClinicalTrials.gov/NCT02491983