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

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

Serena Di Cosimo  1   2   3 , José Manuel Pérez-García  4   2   3 , Meritxell Bellet  5 , Florence Dalenc  6 , Miguel J Gil Gil  7 , Manuel Ruiz Borrego  8 , Joaquín Gavilá  9 , Miguel Sampayo-Cordero  2   10 , Elena Aguirre  2   10 , Peter Schmid  11 , Frederik Marmé  12 , Joseph Gligorov  13 , Andreas Schneeweiss  14 , Joan Albanell  15 , Pilar Zamora  16 , Duncan Wheatley  17 , Eduardo Martínez-De Dueñas  18 , Vicente Carañana  19 , Kepa Amillano  20 , Leonardo Mina  2   10 , Andrea Malfettone  2   10 , Javier Cortés  4   2   3   21 , Antonio Llombart-Cussac  19   22   2   3
Affiliations
Clinical Trial

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

Serena Di Cosimo et al. Oncologist. .

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.

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Conflict of interest statement

Serena Di Cosimo: Novartis, Pierre-Fabre, IQVIA (fees for medical education), Fondazione Associazione Italiana Ricerca contro il Cancro (RF, [AIRC institutional grant IG 20774]), Medica Scientia Innovation Research (C/A, medical advisor); José Manuel Pérez-García: Lilly, Roche, Eisai, Daiichi Sankyo, AstraZeneca, Seattle Genetics (C/A), Roche (travel compensation), Medica Scientia Innovation Research (E); Meritxell Bellet: Pfizer, Novartis, Lilly (C/A, H, speaker’s bureau), Pfizer, Roche (travel compensation); Miguel J. Gil-Gil: Pfizer, Novartis, Eisai (H), Khern, Daiichi, Pfizer, Roche (travel compensation), Daiichi, Agendia, Genomic Health (C/A); Manuel Ruíz-Borrego: Novartis, Pfizer, Merck Sharp & Dohme Corp (C/A), Pfizer, Novartis, Roche, Lilly, AstraZeneca (speaker’s bureau); Joaquín Gavilá: Pfizer, Novartis, Lilly, Merck Sharp & Dohme Corp. (C/A), Pfizer, Novartis, Lilly, Roche (H), Roche (travel compensation), Novartis, Pfizer (speaker’s bureau); Miguel Sampayo-Cordero: Medica Scientia Innovation Research, Syntax for Science, Roche (RF, travel compensation, speaker’s bureau), Medica Scientia Innovation Research, Syntax for Science, Nestlé (C/A, H), Medica Scientia Innovation Research (E); Elena Aguirre: Merck Sharp & Dohme Corp, AstraZeneca, Pfizer, Roche (C/A); Peter Schmid: Pfizer, AstraZeneca, Novartis, Roche, Merck, Boehringer Ingelheim, Bayer, Eisai, Celgene, Puma (C/A), Pfizer, AstraZeneca, Novartis, Roche, Merck, Boehringer Ingelheim (H), Roche, Genentech, Oncogenex, Novartis (RF [institutional grants]); Frederik Marmé: Roche/Genentech, Novartis, AstraZeneca, Eisai, Tesaro, Clovis, Merck Sharp & Dohme Corp Oncology, Vaccibody (RF [institutional]), Roche, Pfizer, Novartis, PharmaMar, AstraZeneca (travel compensation), and serving as a consultant to Tesaro, Pfizer, Novartis, GenomicHealth, CureVac, Amgen, Celgene, Eisai, Janssen-Cilag (C/A), AstraZeneca, Roche, Vaccibody, ImmunoMedics (C/A [institutional]), Roche/Genentech, Novartis, Pfizer, AstraZeneca, Tesaro, Clovis Oncology, Eisai, Celgene, Genomic Health, PharmaMar, Amgen, CureVac, Merck Sharp & Dohme Corp Oncology, Janssen-Cilag, ImmunoMedics (H, to the institution); Joseph Gligorov: Daiichi, Eisai, Genomic Health, Immunomedics, Ipsen, Macrogenics, Merck Sharp & Dohme Corp, Mylan, Novartis, Onxeo, Pfizer, Roche (C/A), Eisai, Genomic Health, Ipsen, Merck Sharp & Dohme Corp, Mylan, Novartis, Pfizer, Roche (speaker’s bureau), Eisai, Genomic Health, Roche (RF), Eisai, Genomic Health, Merck Sharp & Dohme Corp, Mylan, Novartis, Pfizer, Roche (travel compensation); Andreas Schneeweiss: Celgene, Roche, AbbVie, Molecular Partner (RF), Roche, Celgene, Pfizer, AstraZeneca, Novartis, Merck Sharp & Dohme Corp, Tesaro, Lilly (H), Roche, AstraZeneca (ET), Celgene, Roche (travel compensation); Joan Albanell: Pfizer, Roche, Amgen, Merck Sharp & Dohme Corp, Lilly (C/A), Medica Scientia Innovation Research, Roche, Seattle Genetics (RF), Roche, Pfizer (speaker’s bureau), Roche, Pfizer, Amgen, Merck Sharp & Dohme Corp, Lilly (travel compensation), Biocartis (royalties), patents for EGFRmut licensed to Biocartis, for InBiomotion (IP); Pilar Zamora: Roche (RF), Roche, Pfizer (travel compensation); Duncan Wheatley: Pfizer, Roche, Lilly (C/A), Pfizer, Roche, Daiichii Sankyo, Novartis, Lilly (H), Roche (travel compensation), Lilly, Pfizer, Novartis (speaker’s bureau), AstraZeneca (personal fees for work on advisory board); Eduardo Martínez-De Dueñas: Pfizer, Novartis (C/A), Pfizer (H), Roche (travel compensation); Leonardo Mina: Medica Scientia Innovation Research (E); Andrea Malfettone: Medica Scientia Innovation Research (E); Javier Cortés: Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, Merck Sharp & Dohme, GlaxoSmithKline, Leuko, Bioasis, Clovis Oncology (C/A), Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer Healthcare, Eisai, Hoffmann-La Roche, Guardant Health, Merck Sharp & Dohme, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London (RF), Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp & Dohme, Daiichi Sankyo (H), Medica Scientia Innovation Research (IP); Antonio Llombart-Cussac: Lilly, Roche, Pfizer, Novartis, Pierre-Fabre, Genomic Health, GlaxoSmithKline (C/A), Lilly, AstraZeneca, Merck Sharp & Dohme Corp (speaker’s bureau), Roche, Foundation Medicine, Pierre-Fabre, Agendia (RF), Medica Scientia Innovation Research, Initia-Research (IP), Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, Merck Sharp & Dohme Corp. (leadership role), Roche, Lilly, Novartis, Pfizer, AstraZeneca (travel compensation). Florence Dalenc, Vicente Carañana, and Kepa Amillano indicated no financial relationships.

(C/A) Consulting/advisory relationship; (RF) Research funding; (E) Employment; (ET) Expert testimony; (H) Honoraria received; (OI) Ownership interests; (IP) Intellectual property rights/inventor/patent holder; (SAB) Scientific advisory board.

Figures

Figure 1.
Figure 1.
Study follow-up of patients who experienced pulmonary embolism. Asymptomatic grade 3 pulmonary embolism was reported in 10 patients on routine 3-monthly computed tomography scan. In addition, in 5 patients, pulmonary embolism was detected in the context of progressive disease.
Figure 2.
Figure 2.
Progression-free survival landmark analysis for patients with pulmonary embolism who did not discontinued study versus patients without pulmonary embolism. (A) Landmark at 6 months, (B) 8 months, and (C) 12 months.
See this image and copyright information in PMC

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