Efficacy of phase 1 trials in malignant pleural mesothelioma: Description of a series of patients at a single institution

Abstract Background Malignant pleural mesothelioma (MPM) is a locally aggressive disease with a poor prognosis. After failure of first line platinum-based chemotherapy, there is no widely approved salvage regimen. New strategies for treatment are needed and phase 1 trials appear as a rationale alternative. Materials and methods MPM patients were enrolled in 20 different phase 1 trials between March 2005 and January 2012, and their data analyzed retrospectively. The primary endpoint was response rate and secondary endpoints were toxicity profile, overall survival (OS) and progression free survival (PFS). OS and PFS were estimated using Kaplan–Meier and their association with baseline characteristics was investigated through a log-rank test. The drugs described were divided into 5 groups based on their mechanism of action. Results Forty-five patients were analyzed with a median follow up of 20.5 months. The best tumor response was as follows: 4% of patients had a RECIST partial response, 60% had stable disease, 24% had progressive disease and 11% were not evaluable. Grade ≥3 toxicities were observed in 19 (42%) patients. Median OS and PFS were estimated to 6 months (95% CI=[4.2–10.5]) and 2 months (95% CI=[1.3–2.7]), respectively. The cellular motility inhibitors group appeared as the most promising class to be developed in a phase 2 setting. Conclusion Including MPM patients in phase I trials beyond first line of treatment can result in modest clinical benefits with an acceptable toxicity profile. Several molecular pathways involved in MPM have been identified and further novel biologic therapies need to be tested.