Pooled Safety Analysis of Single-Agent Lurbinectedin in Patients With Advanced Solid Tumours.
Lurbinectedin
Phase II
Phase III
Pooled safety
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
received:
13
06
2023
revised:
18
07
2023
accepted:
22
07
2023
medline:
18
9
2023
pubmed:
28
8
2023
entrez:
27
8
2023
Statut:
ppublish
Résumé
Lurbinectedin was approved by FDA and other health regulatory agencies for treating adults with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Safety profile at approved dose (3.2 mg/m Data were pooled from 554 patients: 335 from all nine tumour-specific cohorts of the phase II basket trial and 219 from a randomised phase III trial (CORAIL) in platinum-resistant ovarian cancer. Events and laboratory abnormalities were graded using NCI-CTCAE v.4. Most common tumours were ovarian (n = 219, 40%), SCLC (n = 105, 19%) and endometrial (n = 73, 13%). Transient haematological laboratory abnormalities were the most frequent grade 3 or more events: neutropenia (41%), leukopenia (30%), anaemia (17%) and thrombocytopenia (10%). Most common treatment-emergent non-haematological events (any grade) were transient transaminase increases (alanine aminotransferase [66%], aspartate aminotransferase [53%]), fatigue (63%), nausea (57%), constipation (32%), vomiting (30%) and decreased appetite (25%). Dose reductions were mostly due to haematological toxicities, but most patients (79%) remained on full lurbinectedin dose. Serious events mostly consisted of haematological disorders. Eighteen treatment discontinuations (3%) and seven deaths (1%) were due to treatment-related events. This analysis confirms a manageable safety profile for lurbinectedin in patients with advanced solid tumours. Findings are consistent with those reported in patients with relapsed SCLC, Ewing sarcoma, germline BRCA1/2 metastatic breast cancer, neuroendocrine tumours and ovarian cancer.
Sections du résumé
BACKGROUND
Lurbinectedin was approved by FDA and other health regulatory agencies for treating adults with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Safety profile at approved dose (3.2 mg/m
METHODS
Data were pooled from 554 patients: 335 from all nine tumour-specific cohorts of the phase II basket trial and 219 from a randomised phase III trial (CORAIL) in platinum-resistant ovarian cancer. Events and laboratory abnormalities were graded using NCI-CTCAE v.4.
RESULTS
Most common tumours were ovarian (n = 219, 40%), SCLC (n = 105, 19%) and endometrial (n = 73, 13%). Transient haematological laboratory abnormalities were the most frequent grade 3 or more events: neutropenia (41%), leukopenia (30%), anaemia (17%) and thrombocytopenia (10%). Most common treatment-emergent non-haematological events (any grade) were transient transaminase increases (alanine aminotransferase [66%], aspartate aminotransferase [53%]), fatigue (63%), nausea (57%), constipation (32%), vomiting (30%) and decreased appetite (25%). Dose reductions were mostly due to haematological toxicities, but most patients (79%) remained on full lurbinectedin dose. Serious events mostly consisted of haematological disorders. Eighteen treatment discontinuations (3%) and seven deaths (1%) were due to treatment-related events.
CONCLUSIONS
This analysis confirms a manageable safety profile for lurbinectedin in patients with advanced solid tumours. Findings are consistent with those reported in patients with relapsed SCLC, Ewing sarcoma, germline BRCA1/2 metastatic breast cancer, neuroendocrine tumours and ovarian cancer.
Identifiants
pubmed: 37634282
pii: S0959-8049(23)00361-1
doi: 10.1016/j.ejca.2023.113259
pii:
doi:
Substances chimiques
BRCA1 Protein
0
BRCA1 protein, human
0
BRCA2 Protein
0
BRCA2 protein, human
0
PM 01183
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
113259Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest Vivek Subbiah reports research funding from Pharma Mar and Jazz Pharma to conduct clinical trials; other grant support for clinical trials from AbbVie; Agensys, Inc; Alfasigma; Altum; Amgen; Bayer; BERG Health; Blueprint Medicines Corporation; Boston Biomedical, Inc; Boston Pharmaceuticals; Celgene Corporation; D3 Bio, Inc; Dragonfly Therapeutics, Inc; Exelixis; Fujifilm; GlaxoSmithKline; Idera Pharmaceuticals, Inc; Incyte Corporation; Inhibrx; Loxo Oncology/ Eli Lilly; MedImmune; MultiVir, Inc; Novartis; NanoCarrier, Co; National Comprehensive Cancer Network; NCI-CTEP; Novartis; PharmaMar; Pfizer; Relay Therapeutics; Roche/Genentech; Takeda; Turning Point Therapeutics; UT MD Anderson Cancer Center; and Vegenics Pty Ltd; travel support from ASCO, ESMO, Helsinn Healthcare, Incyte Corporation, Novartis and PharmaMar; consultancy or advisory board participation for Helsinn Healthcare, Incyte Corporation, Loxo Oncology/Eli Lilly, MedImmune, Novartis, QED Therapeutics, Relay Therapeutics, Daiichi-Sankyo and R-Pharm US; and other relationship with Medscape. Cristian Fernandez, Carmen Kahatt, Antonio Nieto and Ali Zeaiter are full-time employees of and own stock from Pharma Mar. Martin Cullell-Young is a full-time employee of Pharma Mar. All other authors declare no competing interests.