Clinical outcomes and prognostic factors of patients with advanced mesothelioma treated in a phase I clinical trials unit

Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): Dionysis Papadatos-Pastos, Desam Roda, Maria Jose De Miguel Luken, Ann Petruckevitch, Awais Jalil, Marta Capelan, Vasiliki Michalarea, Joao Lima, Nikolaos Diamantis, Jaishree Bhosle, L. Rhoda Molife, Udai Banerji, Johann S. de Bono, Sanjay Popat, Mary E.R. O'Brien, Timothy A. Yap
BackgroundWe have previously reported a prognostic score for patients in phase I trials in the Drug Development Unit, treated at the Royal Marsden Hospital (RPS). The RPS is an objective tool used in patient selection for phase I trials based on albumin, number of disease sites and LDH. Patients with mesothelioma are often selected for phase I trials as the disease remains localised for long periods of time. We have now reviewed the clinical outcomes of patients with relapsed malignant mesothelioma (MM) and propose a specific mesothelioma prognostic score (m-RPS) that can help identify patients who are most likely to benefit from early referral.MethodsPatients who participated in 38 phase I trials between September 2003 and November 2015 were included in the analysis. Efficacy was assessed by response rate, median overall survival (OS) and progression-free survival (PFS). Univariate (UVA) and multivariate analyses (MVA) were carried out to develop the m-RPS.ResultsA total of 65 patients with advanced MM were included in this retrospective study. The PFS was 2.5 months (95% confidence interval [CI] 2.0–3.1 months) and OS was 8 months (95% CI 5.6–9.8 months). A total of four (6%) patients had RECIST partial responses, whereas 26 (40%) patients had RECIST stable disease >3 months. The m-RPS was developed comprising of three different prognostic factors: a neutrophil: lymphocyte ratio greater than 3, the presence of more than two disease sites (including lymph nodes as a single site of disease) and albumin levels less than 35 from the MVA. Patients each received a score of 1 for the presence of each factor. Patients in group A (m-RPS 0–1; n = 35) had a median OS of 13.4 months (95% CI 8.5–21.6), whereas those in group B (m-RPS 2–3; n = 30) had a median OS of 4.0 months (95% CI 2.9–7.1, P < 0.0001). A total of 56 (86%) patients experienced G1-2 toxicities, whereas reversible G3-4 toxicities were observed in 18 (28%) patients. Only 10 (15%) patients discontinued phase I trials due to toxicity.ConclusionsPhase I clinical trial therapies were well tolerated with early signals of antitumour activity in advanced MM patients. The m-RPS is a useful tool to assess MM patient suitability for phase I trials and should now be prospectively validated.



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