title: Pathological response after neoadjuvant chemotherapy in resectable non-small-cell lung cancers: proposal for the use of major pathological response as a surrogate endpoint.
abstract: Improvements in outcomes for patients with resectable lung cancers have plateaued. Clinical trials of resectable non-small-cell lung cancers with overall survival as the primary endpoint require a decade or longer to complete, are expensive, and limit innovation. A surrogate for survival, such as pathological response to neoadjuvant chemotherapy, has the potential to improve the efficiency of trials and expedite advances. 10% or less residual viable tumour after neoadjuvant chemotherapy, termed here major pathological response, meets criteria for a surrogate; major pathological response strongly associates with improved survival, is reflective of treatment effect, and captures the magnitude of the treatment benefit on survival. We support the incorporation of major pathological response as a surrogate endpoint for survival in future neoadjuvant trials of resectable lung cancers. Additional prospective studies are needed to confirm the validity and reproducibility of major pathological response within individual histological and molecular subgroups and with new drugs.
authors.affiliation: Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Hellmann
authors.affiliation: Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Chaft
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: William N
authors.initials: WN
authors.lastname: William
authors.affiliation: Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Valerie
authors.initials: V
authors.lastname: Rusch
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Katherine M W
authors.initials: KM
authors.lastname: Pisters
authors.affiliation: Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Neda
authors.initials: N
authors.lastname: Kalhor
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Division of Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Apar
authors.initials: A
authors.lastname: Pataer
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: William D
authors.initials: WD
authors.lastname: Travis
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Division of Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Swisher
authors.affiliation: Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. Electronic address: krism@mskcc.org.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
mesh_terms: D015415:Biomarkers; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging
chemical_list: D015415:Biomarkers