1534P - Efficacy and toxicity observed in malignant pleural mesothelioma patients treated in phase I trials at a single institution

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Anti-Cancer Agents & Biologic Therapy
Mesothelioma
Presenter Jacques Raphael
Authors J. Raphael1, A. Hollebecque2, G. Le Teuff3, C. Massard4, R. Bahleda2, J. Margery5, B. Besse6, J. Soria7, D. Planchard7
  • 1Dept. Medical Oncology, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 2Medical Oncology Department, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 3Department Of Statistics And Epidemiology, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 4Sitep, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 5Pulmonary Department, Percy Hospital, Paris/FR
  • 6Dept. Of Medicine, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 7Thoracic Group, Inserm U981, Institut Gustave Roussy, 94805 - Villejuif/FR

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 I trials appear as a rationale alternative. The results of such an approach have been evaluated. Materials and methods: MPM patients, were enrolled in 20 different phase I trials between March 2005 and January 2012, and their data analysed retrospectively. The primary endpoint was response rate and secondary endpoints were toxicity profile, Overall Survival (OS) and Progression Free Survival (PFS). Median follow-up of patients was estimated through Schemper's method. The cut-off date for the analysis was April 2012. Adverse events were assessed by NCI-CTC v.3.0 and response rate according to RECIST 1.1 criteria.

Results

Forty-six patients with a confirmed histology of MPM were included in the analysis with a median follow up of 20 months. The median age and the sex ratio (M/F) were 61 years old and 2.29 respectively. Radiological disease progression was observed in 50% of pts, clinical progression in 28%, and dose limiting toxicity in 22%. The best tumour response was as follows: 7% of pts had a RECIST partial response, 59% had stable disease for a median duration of 2.8 months and 24% had progressive disease. The median treatment duration in the phase I was 1.9 months. Median OS and PFS were 6 months (95% CI= [4.3-10.7]) and 2.1 months (95% CI= [1.3-2.8]), respectively. The most common grade 3/4 adverse events (41%) were haematological (11%), gastro-intestinal (4%), cutaneous (7%), renal (4%) and hepatic (4%). All adverse events were reversible and no death due to toxicity was reported.

Conclusion

Including MPM pts in phase I trials beyond first line of treatment can result in clinical benefits with an acceptable toxicity profile. Several molecular pathways involved in MPM have been identified and further novel biologic therapies might be tested in a phase I setting in a biology-oriented approach rather than a stochastical one. We are currently offering a tumour molecular profiling in our pts (MOSCATO trial) for a better selection of phase I trial.

Disclosure

All authors have declared no conflicts of interest.