A phase II trial of palbociclib plus letrozole after progression on second-line chemotherapy for women with hormone receptor-positive high-grade serous or endometrioid ovarian, fallopian tube, or peritoneal cancer (LACOG 1018)
- PMID: 40505182
- DOI: 10.1016/j.ygyno.2025.05.022
A phase II trial of palbociclib plus letrozole after progression on second-line chemotherapy for women with hormone receptor-positive high-grade serous or endometrioid ovarian, fallopian tube, or peritoneal cancer (LACOG 1018)
Abstract
Objective: Treatment options for patients with ovarian high-grade serous carcinoma (HGSC) and high-grade endometrioid carcinoma (HGEC) who progress after receiving chemotherapy are limited. Considering that over 80 % of those patients express ER and/or PR, we aimed to evaluate the effectiveness of endocrine therapy combined with CDK inhibitors in this population.
Methods: LACOG 1018, a phase II, single-arm, multicenter trial assessed the efficacy of letrozole 2.5 mg/day continuously plus palbociclib 125 mg/day for 21 days in 28-day cycles in patients with histologically proven ovarian HGSC or HGEC, fallopian tube or peritoneal cancer who had received at least two lines of chemotherapy (including one platinum-based regimen) and progressed on prior chemotherapy. Patients had centrally confirmed hormone positivity - estrogen or progesterone (>10 % by immunohistochemistry). The primary endpoint was investigator-assessed progression-free survival rate at 12 weeks (PFS-week12) by RECIST 1.1.
Results: 41 eligible patients were included (February/2020 to January/2022). The median age was 61 years (range 43-83). The PFS-week12 rate was 63.4 % (95 % CI, 46.8 to 76.1), median PFS 4.2 months (95 % CI, 2.7 to 5.5), and median overall survival 13.4 months (95 % CI, 10.4 to 20.1). The objective response rate was 7.7 % (3 partial responses) and the disease control rate 71.8 %. Treatment-related adverse event rates of any grade and grade 3-4 were 95.1 % and 51.2 %, respectively. Grade 3-4 neutropenia was reported in 17 patients (41.5 %), and febrile neutropenia in 1 (2.4 %).
Conclusions: The combination of Palbociclib plus letrozole has a favorable toxicity profile and appears to have clinical activity in recurrent hormone receptor-positive high-grade ovarian cancer.
Keywords: CDK inhibitor; Endocrine therapy; Endometrioid carcinoma (HGEC); High-grade serous ovarian cancer (HGSC).
Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of competing interest Aknar F. de C. Calabrich: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: (Aknar F. de C. Calabrich reports receiving payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Pfizer, MSD, Takeda, GSK. Support for attending meetings and/or travel from AstraZeneca. Participation in a Data Safety Monitoring Board or Advisory Board of AstraZeneca, Pfizer, MSD, GSK. Leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid from EVA, SBOC. Holds Stock or stock options from AMO.) Andreia Cristina De Melo: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: (Andreia Cristina De Melo reports receiving grants or contracts from Clovis Oncology, AstraZeneca, Novartis, AMGEN, Roche, Regeneron, GSK, MSD, BMS. Consulting fees and participation on Advisory Board from AstraZeneca, Novartis, GSK, MSD, BMS. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Novartis, Sanofi, GSK, MSD, BMS. Support for attending meetings and/or travel from MSD. Role as vice president Brazilian Society of Clinical Oncology.) Angélica N. Rodrigues: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: (Angélica N. Rodrigues reports receiving consulting fees from AstraZeneca, Roche, GSK, MSD, and Eisai. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Roche, GSK, MSD, Eisai, Daichii, Pfizer. Support for attending meetings and/or travel from AstraZeneca, MSD, and Roche. Participation on a Data Safety Monitoring Board or Advisory Board at AstraZeneca, Roche, GSK, MSD, and Eisai. Leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid on SBOC, EVA, and LACOG. Stock or stock options from Dom Clínica de Oncologia.) Elias Abdo Filho: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Fernanda Bronzon Damian: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Graziela Zibetti Dal Molin: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Gustavo Werutsky: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: (Gustavo Werutsky declares receiving payments or honoraria from AstraZeneca, MSD Oncologia, Novartis, Roche, Pfizer, and Daiichi Sankyo/AstraZeneca; having a consulting or advisory role in AstraZeneca, MSD, Novartis, Daiichi Sankyo/AstraZeneca, and Roche; and receiving research grants for the institution from AstraZeneca/MedImmune, Roche/Genentech, GlaxoSmithKline, Novartis, Pfizer, Roche, MSD, Merck, Bayer, Janssen, Astellas Pharma, Libbs, and Takeda.) Mirela Foresti Jiménez: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Rafaela Gomes de Jesus: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Taiane Francieli Rebelatto: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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