title: Progression free survival rate at 9 and 18 weeks predict overall survival in patients with malignant pleural mesothelioma: an individual patient pooled analysis of 10 European Organisation for Research and Treatment of Cancer Lung Cancer Group studies and an independent study validation.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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 9 weeks and 18 weeks 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.
  
  
  RESULTS
  All 10 studies (N=523 patients) were included in the LA of PFSR at 9 and 18 weeks (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-18 weeks 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium. Electronic address: baktiar.hasan@eortc.be.
authors.forename: Baktiar
authors.initials: B
authors.lastname: Hasan
authors.affiliation: Assistance Publique - Hôpitaux de Marseille, Aix Marseille University, Marseille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Greillier
authors.affiliation: European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Pallis
authors.affiliation: European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium.
authors.forename: Jessica
authors.initials: J
authors.lastname: Menis
authors.affiliation: National Cancer Institute, Cairo University, Cairo, Egypt.
authors.forename: Rabab
authors.initials: R
authors.lastname: Gaafar
authors.affiliation: European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium.
authors.forename: Richard
authors.initials: R
authors.lastname: Sylvester
authors.affiliation: University of Leicester, Hodgkin Building, Leicester, United Kingdom.
authors.forename: Dean A
authors.initials: DA
authors.lastname: Fennell
authors.affiliation: Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Baas
authors.affiliation: Ghent University, Gent, Belgium.
authors.forename: Veerle
authors.initials: V
authors.lastname: Surmont
authors.affiliation: Ghent University and Antwerp University Hospital, Belgium.
authors.forename: Jan P
authors.initials: JP
authors.lastname: Van Meerbeeck
authors.affiliation: The Royal Marsden Hospital, Sutton, United Kingdom.
authors.forename: Mary E R
authors.initials: ME
authors.lastname: O'brien
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008654:Mesothelioma / Q000401:mortality* / Q000628:therapy*; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000401:mortality* / Q000628:therapy*; D011379:Prognosis; D015203:Reproducibility of Results; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
keywords: Malignant pleural mesothelioma (MPM); Overall survival (OS) prediction; Progression free survival rates at 9 and 18weeks (PFSR-9 and 18); Response rates