Lurbinectedin in patients with pretreated neuroendocrine tumours: Results from a phase II basket study

Abstract

Background: Patients with neuroendocrine tumours (NETs) need alternative therapies after failure of first-line therapy.

Patients and methods: This phase II trial evaluated lurbinectedin, a selective inhibitor of oncogenic transcription, at 3.2 mg/m2 as a 1-h intravenous infusion every 3 weeks in 32 NETs patients treated in the second- or third-line setting. The primary efficacy endpoint was overall response rate (ORR) according to RECIST v1.1 assessed by the investigators. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety.

Results: Two of 31 evaluable patients had confirmed partial responses (ORR = 6.5%; 95%CI, 0.8-21.4%). Median DoR was 4.7 months (95% CI, 4.0-5.4 months), median PFS was 1.4 months (95% CI, 1.2-3.0 months) and median OS was 7.4 months (95% CI, 3.4-16.2 months). Lurbinectedin showed an acceptable, predictable and manageable safety profile. The most common grade 3/4 toxicity was neutropenia (40.6%; grade 4, 12.4%; febrile neutropenia, 3.1%).

Conclusions: Considering the exploratory aim of this trial that evaluated a heterogeneous population of NETs patients, and the signs of antitumour activity observed (two confirmed partial responses and seven long disease stabilisations), further development of lurbinectedin is warranted in a more selected NETs population.

Trial registration number: Sponsor Study Code: PM1183-B-005-14. EudraCT number: 2014-003773-42.

Clinicaltrials: gov reference: NCT02454972.

Keywords: Lurbinectedin; Neuroendocrine tumours; Phase II trial; Small cell.

Conflict of interest statement

Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Cristian Fernández, Carmen Kahatt, Vicente Alfaro, Mariano Siguero and Ali Zeaiter are permanent employees of PharmaMar. Victor Moreno reports consulting fees from Roche, Bayer, BMS, Janssen and Basilea. Vivek Subbiah reports grants from Pharmamar, Eli Lilly/LOXO Oncology, Blueprint Medicines Corporation, Turning Point Therapeutics, Boston Pharmaceuticals; and grants from Helsinn Pharmaceuticals during the conduct of the study; in addition, Vivek Subbiah reports a grant and advisory board/consultant position with Eli Lilly/Loxo Oncology during the conduct of the study; research grants from Roche/Genentech, Bayer, GlaxoSmithKline, Nanocarrier, Vegenics, Celgene, Northwest Biotherapeutics, Berghealth, Incyte, Fujifilm, D3, Pfizer, Multivir, Amgen, Abbvie, Alfa-sigma, Agensys, Boston Biomedical, Idera Pharma, Inhibrx, Exelixis, Blueprint Medicines, Altum, Dragonfly Therapeutics, Takeda, National Comprehensive Cancer Network, NCI-CTEP, University of Texas MD Anderson Cancer Center, Turning Point Therapeutics, Boston Pharmaceuticals, Novartis, Pharmamar, Medimmune; an advisory board/consultant position with Helsinn, Incyte, QED Pharma, Daiichi-Sankyo, Signant Health, Novartis, Janssen, Relay Therapeutics, Roche, Medimmune; travel funds from Pharmamar, Incyte, ASCO, ESMO; other support from Medscape; all outside the submitted work. No disclosures were reported by the other authors.

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