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Adding an antibody against the tumour's blood supply to chemotherapy pushed median survival past a year for the first time in advanced lung cancer, at the cost of more treatment-related deaths.
The Eastern Cooperative Oncology Group's E4599 trial, reported by Sandler, Gray, Perry, Brahmer, Schiller, Dowlati, Lilenbaum and Johnson: 878 patients with recurrent or advanced stage IIIB or IV non-small-cell lung cancer randomised between July 2001 and April 2004 to paclitaxel and carboplatin alone (444) or with bevacizumab continued until progression (434).
Patients with squamous tumours, brain metastases, clinically significant haemoptysis, inadequate organ function or a performance status above 1 were excluded, because of fatal pulmonary haemorrhage seen in earlier studies. That exclusion list is part of the result: it is the first modern lung cancer trial in which a biological feature of the tumour decided who could receive the drug.
The first time a targeted biological agent extended survival in lung cancer, and the first time median survival in the advanced setting crossed twelve months. It also set the pattern that a drug's exclusion criteria can matter as much as its mechanism.
Shares Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer, Performance status (ECOG, Karnofsky), ECOG-ACRIN Cancer Research Group, 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 Histology, 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, Biomarkers are not validated or standardised and the tag lung-evidence.
Shares Brain metastases (intracranial disease), 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, New England Journal of Medicine 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, Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall, Biomarkers are not validated or standardised and the tag lung-evidence.
Shares Brain metastases (intracranial disease), 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 enrol too few, too slowly, Biomarkers are not validated or standardised 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, Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall, Biomarkers are not validated or standardised and the tag lung-evidence.
Shares 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, Paclitaxel / nab-paclitaxel, New England Journal of Medicine, Carboplatin and the tag lung-evidence.
Shares Histology, 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, Lung cancer (all types), Non-small-cell lung cancer and the tag lung-evidence.