BACKGROUND: Systemic second- and third-line therapies for malignant pleural mesothelioma (MPM) result in a median progression-free survival (mPFS) of <2 months and median overall survival (mOS) of 6-9 months. Lurbinectedin binds to the regulatory region DNA whilst inhibiting tumour-associated macrophage transcription. In early trials, encouraging outcomes occurred in MPM patients (pts) treated with lurbinectedin. We aimed to generate lurbinectedin efficacy and safety data among pts with progressive MPM.
PATIENTS AND METHODS: Progressing MPM patients treated with first-line platinum-pemetrexed chemotherapy with or without immunotherapy received lurbinectedin monotherapy. Treatment was given intravenously at 3.2mg/m2 dose every three weeks, until progression or unacceptable toxicity. Using a Simon’s two-stage design, the primary endpoint, PFS at 12 weeks (PFS12wks), was met if achieved by ?21 pts (p0 ?35% vs p1 ?55%).
RESULTS: Forty-two pts from nine centres across Switzerland and Italy were recruited. Histology was epithelioid in 33, sarcomatoid in five, and biphasic in four cases. Overall, 10/42 (23.8%) underwent prior immunotherapy and 14/42 (33.3%) had progressed ?6 months after first-line chemotherapy. At data cut-off, PFS12wks was met by 22/42 patients (52.4%; 90% CI: 38.7-63.5%; P=0.015) with an mPFS of 4.1 months and mOS of 11.1 months. The best response was complete and partial remission observed in one patient each and stable disease in 20 pts. Duration of disease control was 6.6 months (95% CI: 5.2-7.4). No significant difference in PFS12wks, mPFS, and mOS was recorded in epithelioid vs non-epithelioid cases and pts with prior immunotherapy vs those without. Similar mPFS but shorter mOS were observed among pts who progressed within ?6 months after first-line chemotherapy. Lurbinectedin-related grade 3-4 toxicity was seen in 21 pts, mostly being neutropenia (23.8%) and fatigue (16.7%).
CONCLUSIONS: The primary efficacy endpoint was reached with acceptable toxicity. Lurbinectedin showed promising activity regardless of histology, prior immunotherapy, or outcome on prior treatment.
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