Short Report of a Phase II Trial of Nintedanib in Recurrent Malignant Pleural Mesothelioma (MPM).

BACKGROUND

: Malignant pleural mesothelioma (MPM) is a disease for which there remains an unmet need for better therapeutic options. Nintedanib is an oral multikinase inhibitor impacting VEGF, FGF, PDGFR, and other kinase activity such as TGFß signaling pathways. We conducted a phase II trial of nintedanib in patients with recurrent MPM.

METHODS

: Patients with MPM previously treated with platinum-based chemotherapy, performance status (PS) 0–1, adequate organ function, and no contraindications to anti-angiogenic therapy were eligible and were treated with nintedanib 200 mg twice per day until disease progression or unacceptable toxicity. The primary endpoint was 4-month progression-free survival (PFS).

RESULTS

: Twenty patients were enrolled. The median age was 70 years (range 32–81), 90% were male, and 80% were PS 1. The histology was 70% epithelioid, 5% sarcomatoid, 10% biphasic, and 15% unknown. 15% had prior bevacizumab. The median follow-up was 4.1 mo. There were no responses but 40% had stable disease at 8 weeks. The median PFS was 1.8 mo. (95% CI: 1.68, 3.55) and the 4-month PFS rate was 13%. The median OS was 4.2 mo. (95% CI: 2.53, 8.74) and the 4-month OS rate was 55%. Toxicities were primarily grade 1–2 and included diarrhea, fatigue, edema, transaminase elevation, anorexia, nausea, vomiting and dyspnea.

CONCLUSIONS

: The activity of nintedanib in previously treated MPM patients was. modest. The trial did not meet its primary PFS endpoint. Even though 2 patients had prolonged stable disease for >4 months, the efficacy of nintedanib remains unproven.