Efficacy and safety of lurbinectedin and doxorubicin in relapsed small cell lung cancer. Results from an expansion cohort of a phase I study

Abstract

Background A phase I study found remarkable activity and manageable toxicity for doxorubicin (bolus) plus lurbinectedin (1-h intravenous [i.v.] infusion) on Day 1 every three weeks (q3wk) as second-line therapy in relapsed small cell lung cancer (SCLC). An expansion cohort further evaluated this combination. Patients and methods Twenty-eight patients with relapsed SCLC after no more than one line of cytotoxic-containing chemotherapy were treated: 18 (64%) with sensitive disease (chemotherapy-free interval [CTFI] ≥90 days) and ten (36%) with resistant disease (CTFI <90 days; including six with refractory disease [CTFI ≤30 days]). Results Ten patients showed confirmed response (overall response rate [ORR] = 36%); median progression-free survival (PFS) = 3.3 months; median overall survival (OS) = 7.9 months. ORR was 50% in sensitive disease (median PFS = 5.7 months; median OS = 11.5 months) and 10% in resistant disease (median PFS = 1.3 months; median OS = 4.6 months). The main toxicity was transient and reversible myelosuppression. Treatment-related non-hematological events (fatigue, nausea, decreased appetite, vomiting, alopecia) were mostly mild or moderate. Conclusion Doxorubicin 40 mg/m2 and lurbinectedin 2.0 mg/m2 on Day 1 q3wk has shown noteworthy activity in relapsed SCLC and a manageable safety profile. The combination is being evaluated as second-line therapy for SCLC in an ongoing, randomized phase III trial. Clinical trial registration www.ClinicalTrials.gov code: NCT01970540. Date of registration: 22 October, 2013.

Keywords: Lurbinectedin; PM01183; Phase I study; Small cell lung cancer.

Conflict of interest statement

Martin Forster has conducted consulting and advisory services, speaking or writing engagements, or public presentations for Achilles, AstraZeneca, Bayer, BMS, Celgene, Guardant Health, Merck, MSD, Nanobiotix, Novartis, Oxford VaMedix, Pfizer, Pfizer, Roche and Takeda; his institution has received research funding from AstraZeneca, Boehringer Ingelheim, MSD and Merck; in addition, Martin Foster is supported by the UCL/UCLH NIHR Biomedical Research Centre and runs early phase studies in the NIHR UCLH Clinical Research Facility supported by the UCL ECMC. Emiliano Calvo has had a company leadership role, employment relationship or ownership interest for START Madrid, Oncoart Associated, International Cancer Consultants and HM Hospitals Group; has conducted consulting and advisory services, speaking or writing engagements, or public presentations for Astellas Pharma, Novartis, Nanobiotix, Pfizer, Janssen, GLG, Merck, Medscape, BMS, Pierre-Fabre, Gilead, Cerulean, Gehrman Consulting, Boehringen-Ingelheim, Seattle Genetics, Guidepoint, AstraZeneca, Roche/Genetech, PsiOxus, Abbvie, Celgene, Servier and Amcure; has been study international principal investigator for AstraZeneca and member of study steering committees for Novartis and BeiGene, and his institution has received financial support from Abbvie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Janssen Oncology, Hospira, Lilly, Merck, Merus, Millennium, Nanobiotix, Nektar. Novartis, OncoMed, Pfizer, PharmaMar, PsiOxus Therapeutics, Puma Biotechnology, Regeneron, Roche-Genentech, Sanofi, Spectrum Pharmaceuticals, ACEA Bio, Amcure, Cytomx, H3-Biomedicine, Incyte, Kura, LOXO, Macrogenics, Menarini, Principia, Tahio, Tesaro, BeiGene, Transgene, Takeda, Innovio, MSD, Seattle Genetics, Mersana, GSK, Daiichi, Astellas, ORCA, Boston Therapeutics, Dynavax, DebioPharma, Synthon and Rigontec. José Antonio López-Vilariño, Rafael Núñez, Carmen Kahatt and Ali Zeaiter are employees and stock owners of Pharma Mar, S.A. Martin Cullell-Young is an employee of Pharma Mar, S.A. All remaining authors have declared no conflicts of interest.

© 2021. The Author(s).

Figures

Fig. 1

Waterfall plot showing maximum variation of target lesions and progression-free survival in patients with at least one radiological tumor assessment (n = 26). Ten patients had target lesion decrease >30%: one with CR and nine with PR. Red stars = treatment switch to lurbinectedin alone. CR, complete response; CTFI, chemotherapy-free interval; d, days; PR, partial response