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The second of the two 2004 papers that found EGFR mutations. It also explained why Japanese patients responded to gefitinib far more often than American ones: the mutation was simply much more common in Japan.
Paez, Jänne, Lee and colleagues at the Dana-Farber Cancer Institute and the Broad Institute, with Meyerson as senior author, sequenced receptor tyrosine kinase genes in non-small-cell lung cancer and matched normal tissue, then looked for the same mutations in responders to gefitinib and in a hypersensitive cell line.
The geographic difference it documented is the paper's second contribution. A response rate that varied by country had been read as a difference in practice or reporting; it turned out to be a difference in the prevalence of a mutation, which is the first demonstration in lung cancer that tumour genotype, not population, explains a drug's performance.
Why a drug can look useless in one trial and transformative in another: the trials had different proportions of the patients the drug was for. It is the argument for genotyping before drawing conclusions from a response rate.
The trial that turned EGFR testing into a standard of care rather than a research assay, and the clearest demonstration in oncology that a clinically selected population can hide two opposite treatment effects inside one positive result.
The template for every driver mutation since: find the responders, sequence them, and give the drug only to people whose tumour carries the lesion it was built for. Gefitinib had been close to abandonment on the strength of unselected trials.
Shares Matthew Meyerson, Pasi A. Jänne, Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib, Gefitinib and the tag lung-evidence.
Shares Oncogene addiction, Adenocarcinoma of the lung, Driver mutation, Next-generation sequencing (NGS) and the tag lung-evidence.
Shares Pasi A. Jänne, Oncogene addiction, Driver mutation, Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch and the tag lung-evidence.
Shares Adenocarcinoma of the lung, Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch, Trials do not represent the people who get cancer, EGFR-mutated non-small-cell lung cancer and the tag lung-evidence.
Shares Adenocarcinoma of the lung, Driver mutation, Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch, EGFR and the tag lung-evidence.
Shares Driver mutation, Next-generation sequencing (NGS), Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch, Biomarkers are not validated or standardised and the tag lung-evidence.
Shares Driver mutation, Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch, Biomarkers are not validated or standardised, EGFR-mutated non-small-cell lung cancer and the tag lung-evidence.
Shares Adenocarcinoma of the lung, Driver mutation, Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch, EGFR and the tag lung-evidence.