Di Cosimo, SerenaPérez-García, José ManuelBellet, MeritxellDalenc, FlorenceGil Gil, Miguel JRuiz Borrego, ManuelGavilá, JoaquínSampayo-Cordero, MiguelAguirre, ElenaSchmid, PeterMarmé, FrederikGligorov, JosephSchneeweiss, AndreasAlbanell, JoanZamora, PilarWheatley, DuncanMartínez-De Dueñas, EduardoCarañana, VicenteAmillano, KepaMina, LeonardoMalfettone, AndreaCortés, JavierLlombart-Cussac, Antonio2023-05-032023-05-032023http://hdl.handle.net/10668/19828Palbociclib 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. 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. 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  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. NCT02491983; https://clinicaltrials.gov/ct2/show/NCT02491983).enAttribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/advanced breast cancerendocrine therapyinterstitial lung diseaseneutropeniapalbociclibpneumonitisvenous thromboembolismFemaleHumansAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsFulvestrantLetrozolePulmonary EmbolismReceptor, ErbB-2Receptors, EstrogenVenous Thromboembolismresearch article36239405open access10.1093/oncolo/oyac2051549-490XPMC9847524https://academic.oup.com/oncolo/article-pdf/28/1/23/48837357/oyac205.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9847524/pdf