1316 - SAKK 17/16: Lurbinectedin as second or third line palliative chemotherapy in malignant pleural mesothelioma (MPM): A multi-center, single-arm Phase II trial.

Background

Available systemic 2^nd or 3^rd line options for MPM show a median progression-free survival (mPFS) of less than 2 months (mo) and median overall-survival (mOS) of 6-9 mo. Lurbinectedin (PharmaMar) is a novel compound with a dual role of binding to the DNA minor groove and inhibiting cytokine transcription of tumor-associated macrophages. Single MPM pts treated with lurbinectedin in early clinical trials showed encouraging outcome. The aim of current trial was to provide further data on safety and efficacy of lurbinectedin in progressive MPM.

Methods

MPM pts (all histologies) not amenable for local treatment and progressing after first-line platinum-pemetrexed chemotherapy +/- immunotherapy (IO) received 2^nd or respectively 3^rd line lurbinectedin. Lurbinectedin 3.2 mg/m² every 3 weeks was given i.v. until progression or unacceptable toxicity. Primary endpoint was PFS at 12 weeks (PFS_12wks) and would be met if achieved by at least 21 pts (p0 ≤ 35%; mPFS 2 mo). Secondary endpoints were mPFS, mOS and adverse events (AEs).

Results

6 Swiss and 3 Italian centers recruited 42 pts (33 epithelioid, 4 biphasic, 5 sarcomatoid). 10/42 (23.8%) pts also received prior IO. At cut-off date (31^st January 2019) PFS_12wks was met by 22/42 pts (52.4%; 95%CI [38.7%; 63.5%]; p = 0.015) for mPFS of 4.1mo (95% CI [2.6; 5.5]) and mOS of 11.9mo (95% CI [9.2; 14.7]). 1 pt had complete, 1 pt partial response and 20 pts stable disease as best response. No significant difference in PFS_12wks, mPFS and mOS was observed in epithelioid vs non-epithelioid MPM and prior-IO vs non-prior IO pts. All pts experienced AEs. Grade 3-4 toxicity was seen in 33 pts with most common being leuco-/lymphopenia (60.6%) and fatigue (24.2%). Febrile neutropenia was 9.1%. No pt discontinued treatment due to toxicity.

Conclusions

The primary efficacy endpoint was reached with acceptable toxicity. Lurbinectedin showed promising activity compared to historical data. Neither histology nor prior IO seems to affect efficacy of lurbinectedin, but respective pts numbers are small for definitive conclusions. Further evaluation of lurbinectedin in a large randomized trial is warranted.

Clinical trial identification

NCT03213301.

Editorial acknowledgement

Legal entity responsible for the study

Swiss Group for Clinical Cancer Research.

Funding

PharmaMar; State Secretariat for Education, Research and Innovation (SERI).

Disclosure

Y. Metaxas: Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (institution), Advisory / Consultancy: Merck; Travel / Accommodation / Expenses: PharmaMar; Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol Meyer Squibb; Honoraria (institution), Advisory / Consultancy: MSD; Research grant / Funding (institution): Krebsliga Graubünden; Research grant / Funding (institution): Suva Switzerland. M. Frueh: Honoraria (institution), Advisory / Consultancy: BMS; Honoraria (institution), Advisory / Consultancy: MSD; Honoraria (institution), Advisory / Consultancy: AstraZeneca; Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (institution), Advisory / Consultancy: Takeda. F. Grosso: Travel / Accommodation / Expenses: Novocure; Travel / Accommodation / Expenses: PharmaMar; Travel / Accommodation / Expenses: Boehringer Ingelheim; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Bristol-Meyer Squibb; Travel / Accommodation / Expenses: Amianto-Italia-Canada-Asbestos Committee; Honoraria (self): Merck; Honoraria (self): Italian Centro per la Prevenzione e Controllo delle Malattie; Research grant / Funding (self): Associazione Famigliari e Vittime Amianto. P.A. Zucali: Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Novartis; Advisory / Consultancy: Merck Sharp and Dohme; Honoraria (self): Pfizer; Honoraria (self): Ipsen; Honoraria (self): Tesaro. G.L. Ceresoli: Honoraria (self), Advisory / Consultancy: Boehringer-Ingelheim; Advisory / Consultancy: Merck Sharp and Dohme; Honoraria (self): Astellas; Honoraria (self): Pfizer; Travel / Accommodation / Expenses: Novocure. M.T. Mark: Honoraria (institution), Advisory / Consultancy: BMS; Honoraria (institution), Advisory / Consultancy: MSD; Honoraria (institution), Advisory / Consultancy: Boehringer; Honoraria (institution), Advisory / Consultancy: AstraZeneca; Honoraria (institution), Advisory / Consultancy: Takeda. M.R.A. Perrino: Honoraria (self): Astellas; Honoraria (self): Bristol Meyer Squibb; Honoraria (self): Novartis. S. Schmidt: Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Research grant / Funding (institution): BMS; Research grant / Funding (institution): AstraZeneca; Travel / Accommodation / Expenses: Takeda. R. von Moos: Honoraria (institution), Advisory / Consultancy: Amgen; Advisory / Consultancy: Bayer; Advisory / Consultancy: Elly Lilly; Advisory / Consultancy: Novartis; Honoraria (institution), Advisory / Consultancy: Roche; Advisory / Consultancy: Sanofi Aventis; Advisory / Consultancy: Merck-Serono; Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro; Advisory / Consultancy: Bristol-Meyers ; Advisory / Consultancy: MSD; Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Vifor. All other authors have declared no conflicts of interest.