European Journal of Cancer. 2014 August 21. [Epub ahead of print] [Link]
Hasan B, Greillier L, Pallis A, Meis J, Gaafar R, Sylvester R, Fennell DA, Baas P, Surmont V, Van Merbeeck JP, O’brien ME.
Response criteria have always been difficult to apply to malignant pleural mesothelioma (MPM), due to its unique pattern of growth. We developed some models to show that progression free survival rate (PFSR) could be a better predictor of overall survival (OS) than the response rate (RR) in MPM patients. The results were validated independently in the European Organisation for Research and Treatment of Cancer (EORTC) 08052, a phase II study in MPM.
Individual patient data from 10 EORTC-Lung Cancer Group (LCG) studies of first-line chemotherapy in MPM were pooled. Response to therapy was assessed according to World Health Organisation (WHO) criteria in all except the two most recent trials, which used Response Evaluation Criteria in Solid Tumours (RECIST). Landmark analyses (LA) at 9weeks and 18weeks after registration/randomisation were performed to assess the association between PFSR and OS. Independent validation of the results was conducted in EORTC 08052 study (82 patients) employing the same LA.
All 10 studies (N=523 patients) were included in the LA of PFSR at 9 and 18weeks (PFSR-9 and PFSR-18). PFSR-9 and PFSR-18 were confirmed as predictors of OS, with hazard ratio (HR) of 0.37 (95% confidence interval (CI), 0.30-0.47) and 0.50 (0.38-0.65) and C-index of 0.62 and 0.58, respectively. In the validation study, 28.4% achieved CR/PR and 77.8% had disease control (CR/PR/SD) as their best overall response. PFSR-9 and PFSR-18weeks were both strongly correlated with OS (HR of 0.35 [80% CI, 0.25-0.49] and 0.46 (0.32-0.67) and C-index of 0.66 and 0.60, respectively).
PFSR-18 was strongly correlated and discriminated patients with better OS from the poorer prognosis patients. An earlier end-point, PFSR-9 was also strongly correlated to OS with better discriminating capacity. The results were independently validated.