{"entity":{"id":"paper-sandler-ecog-4599-bevacizumab-nsclc-nejm-2006","kind":"paper","name":"Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer","aka":[],"tldr":"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.","summary":"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).\n\nPatients 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.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2006","url":"https://doi.org/10.1056/NEJMoa061884"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/17167137/"},{"label":"ClinicalTrials.gov NCT00021060","url":"https://clinicaltrials.gov/study/NCT00021060"}],"tags":["lung-evidence"],"related":["paper-scagliotti-cisplatin-pemetrexed-histology-jco-2008","targeted-therapy-roadmap"],"cancers":["lung-cancer","nsclc","lung-adenocarcinoma"],"sections":[],"technologies":[],"targets":["vegf"],"drugs":["bevacizumab","paclitaxel","carboplatin"],"companies":["ecog-acrin"],"institutions":[],"pathways":["angiogenesis"],"terms":["brain-metastases","performance-status","histology"],"trials":[],"people":["julie-brahmer"],"bottlenecks":["b-biomarker-validation","b-toxicity-qol","b-trial-enrolment"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2006,"doi":"10.1056/NEJMoa061884","pmid":"17167137","authors":"Sandler A, Gray R, Perry MC, et al.","paperType":"rct","findings":["Median survival 12.3 months with bevacizumab against 10.3 months with chemotherapy alone (hazard ratio for death 0.79; P equals 0.003).","Median progression-free survival 6.2 against 4.5 months (hazard ratio 0.66).","The survival benefit came with a risk of increased treatment-related deaths.","Patients with squamous tumours, brain metastases, significant haemoptysis, inadequate organ function or performance status above 1 were excluded from the trial."],"whatItMeans":"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.","caveats":["Non-squamous histology only, with brain metastases excluded; the result does not transfer to the patients who were kept out.","Treatment-related deaths were higher with bevacizumab, and the abstract does not quantify them.","No predictive biomarker for benefit was ever validated, so bevacizumab is given to a histologically rather than molecularly defined group."],"changedPractice":true,"participants":878},"route":"/key-papers/paper-sandler-ecog-4599-bevacizumab-nsclc-nejm-2006/","neighbours":{"paper":[{"id":"paper-scagliotti-cisplatin-pemetrexed-histology-jco-2008","kind":"paper","name":"Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer","route":"/key-papers/paper-scagliotti-cisplatin-pemetrexed-histology-jco-2008/"}],"roadmap":[{"id":"lung-cancer-evidence-roadmap","kind":"roadmap","name":"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","route":"/roadmaps/lung-cancer-evidence-roadmap/"},{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"}],"cancer":[{"id":"lung-adenocarcinoma","kind":"cancer","name":"Adenocarcinoma of the lung","route":"/cancers/lung-adenocarcinoma/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"target":[{"id":"vegf","kind":"target","name":"VEGF / VEGFR","route":"/targets/vegf/"}],"drug":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"}],"company":[{"id":"ecog-acrin","kind":"company","name":"ECOG-ACRIN Cancer Research Group","route":"/companies/ecog-acrin/"}],"term":[{"id":"angiogenesis","kind":"term","name":"Angiogenesis","route":"/terms/angiogenesis/"},{"id":"brain-metastases","kind":"term","name":"Brain metastases (intracranial disease)","route":"/terms/brain-metastases/"},{"id":"histology","kind":"term","name":"Histology","route":"/terms/histology/"},{"id":"performance-status","kind":"term","name":"Performance status (ECOG, Karnofsky)","route":"/terms/performance-status/"}],"person":[{"id":"julie-brahmer","kind":"person","name":"Julie R. Brahmer","route":"/people/julie-brahmer/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"},{"id":"b-trial-enrolment","kind":"bottleneck","name":"Trials enrol too few, too slowly","route":"/bottlenecks/b-trial-enrolment/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}