Lurbinectedin in Patients With Pretreated Endometrial Cancer: Results From a Phase 2 Basket Clinical Trial and Exploratory Translational Study

Authors

Rebecca Kristeleit
Alexandra Leary
Jean Pierre Delord
Victor Moreno
Ana Oaknin
Daniel Castellano
Geoffrey I Shappiro
Cristian Fernández
Carmen Kahatt
Vicente Alfaro
Mariano Siguero
Daniel Rueda
Ali Zeaiter
Ahmad Awada
Ana Santaballa
Khalil Zaman
Jalid Sehouli
Vivek Subbiah

Publication Date

10-1-2023

Journal

Investigational New Drugs

Abstract

Second-line treatment of endometrial cancer is an unmet medical need. Lurbinectedin showed promising antitumor activity in a phase I study in combination with doxorubicin in advanced endometrial cancer. This phase 2 Basket trial evaluated lurbinectedin 3.2 mg/m2 1-h intravenous infusion every 3 weeks in a cohort of 73 patients with pretreated endometrial cancer. The primary endpoint was overall response rate (ORR) according to RECIST v1.1. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), safety and an exploratory translational study. Confirmed complete (CR) and partial response (PR) was reported in two and six patients, respectively (ORR = 11.3%; 95%CI, 5.0-21.0%). Median DoR was 9.2 months (95%CI, 3.4-18.0 months), median PFS was 2.6 months (95%CI, 1.4-4.0 months) and median OS was 9.3 months (95%CI, 6.1-12.8 months). Molecular subtypes showed differences in PFS rate at 6 months (p53abn 23.7% vs. "No Specific Molecular Profile" [NSMP] 42.9%) and median OS (p53abn 6.6 months vs. NSMP 16.1 months). The most common treatment-related adverse events (mostly grade 1/2) were fatigue (54.8% of patients), nausea (50.7%), vomiting (26.0%) decreased appetite (17.8%). and constipation, (19.2%). The most common grade 3/4 toxicity was neutropenia (43.8%; grade 4, 19.2%; febrile neutropenia, 4.1%). In conclusion, considering the exploratory aim of this trial and the hints of antitumor activity observed together with a predictable and manageable safety profile, further biomarker-based development of lurbinectedin is recommended in this indication in combination with other agents. Clinicaltrials.gov identifier: NCT02454972.

Keywords

Female, Humans, Antineoplastic Combined Chemotherapy Protocols, Carbolines, Doxorubicin, Endometrial Neoplasms, Neutropenia, Lurbinectedin, Endometrial cancer, Phase 2

DOI

10.1007/s10637-023-01383-2

PMID

37556023

PMCID

PMC10560193

PubMedCentral® Posted Date

8-9-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes