Lancet Oncol. 2014 Jan;15(1):e42-50. doi: 10.1016/S1470-2045(13)70334-6.

Pathological response after neoadjuvant chemotherapy in resectable non-small-cell lung cancers: proposal for the use of major pathological response as a surrogate endpoint.

Hellmann MD1, Chaft JE1, William WN Jr2, Rusch V3, Pisters KM2, Kalhor N4, Pataer A5, Travis WD6, Swisher SG5, Kris MG7; University of Texas MD AndersonLung Cancer Collaborative Group.

Author information

• 1Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
• 2Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
• 3Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
• 4Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
• 5Department of Thoracic and Cardiovascular Surgery, Division of Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
• 6Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
• 7Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. Electronic address: krism@mskcc.org.

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.