{"entity":{"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","aka":[],"tldr":"1,725 patients, two chemotherapy combinations, identical survival overall. But split by what the tumour looked like down a microscope, one drug was better for adenocarcinoma and the other for squamous cancer. Histology started choosing the drug.","summary":"Scagliotti, Parikh, von Pawel and colleagues randomised 1,725 chemotherapy-naive patients with advanced non-small-cell lung cancer to cisplatin with gemcitabine (863) or cisplatin with pemetrexed (862) for up to six cycles, in a non-inferiority design.\n\nThe overall result was non-inferiority, which by itself would have changed little. The pre-specified histology analysis is what changed practice: pemetrexed was better in adenocarcinoma and large-cell carcinoma and worse in squamous cell carcinoma, a difference attributed to thymidylate synthase expression. This is the first phase 3 trial in lung cancer to show survival differences by histological type, and the reason a pathologist's subtype now has to be recorded before chemotherapy is chosen.","asOf":"2026-09-25","links":[{"label":"J Clin Oncol 2008","url":"https://doi.org/10.1200/JCO.2007.15.0375"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/18506025/"},{"label":"JCO 2023 reprint","url":"https://europepmc.org/article/MED/37146426"}],"tags":["lung-evidence"],"related":["chemotherapy-roadmap","paper-schiller-ecog-1594-four-chemotherapy-regimens-nejm-2002","paper-keynote-189-nejm-2018"],"cancers":["lung-cancer","nsclc","lung-adenocarcinoma","lung-squamous-cell-carcinoma"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":["cisplatin","pemetrexed","gemcitabine"],"companies":[],"institutions":[],"pathways":[],"terms":["histology"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-dose-optimisation"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2008,"doi":"10.1200/JCO.2007.15.0375","pmid":"18506025","authors":"Scagliotti GV, Parikh P, von Pawel J, et al.","paperType":"rct","findings":["Overall survival for cisplatin and pemetrexed was non-inferior to cisplatin and gemcitabine: median 10.3 against 10.3 months, hazard ratio 0.94 (95 percent confidence interval 0.84 to 1.05).","In adenocarcinoma (847 patients) survival was superior with pemetrexed: 12.6 against 10.9 months.","In large-cell carcinoma (153 patients) survival was superior with pemetrexed: 10.4 against 6.7 months.","In squamous cell histology (473 patients) survival was superior with gemcitabine: 10.8 against 9.4 months.","Cisplatin and pemetrexed caused less grade 3 or 4 neutropenia, anaemia and thrombocytopenia, less febrile neutropenia and less alopecia; nausea was more common.","The first prospective phase 3 study in non-small-cell lung cancer to show survival differences based on histological type."],"whatItMeans":"The moment lung cancer stopped being one disease for treatment purposes. Before this trial the pathology report said cancer or not cancer; after it, the subtype chose the drug, and the tissue had to be preserved well enough to answer the question.","caveats":["The histology effects were subgroup analyses within a non-inferiority trial, and the biological explanation (thymidylate synthase) was proposed rather than measured prospectively.","Predates molecular testing, so the adenocarcinoma arm mixes EGFR-mutant, ALK-positive and driver-negative disease.","Cross-trial comparison with modern regimens is not valid: these patients received neither maintenance therapy nor immunotherapy."],"changedPractice":true,"participants":1725},"route":"/key-papers/paper-scagliotti-cisplatin-pemetrexed-histology-jco-2008/","neighbours":{"roadmap":[{"id":"chemotherapy-roadmap","kind":"roadmap","name":"Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs","route":"/roadmaps/chemotherapy-roadmap/"}],"paper":[{"id":"paper-schiller-ecog-1594-four-chemotherapy-regimens-nejm-2002","kind":"paper","name":"Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer","route":"/key-papers/paper-schiller-ecog-1594-four-chemotherapy-regimens-nejm-2002/"},{"id":"paper-keynote-189-nejm-2018","kind":"paper","name":"KEYNOTE-189: pembrolizumab plus chemotherapy as first treatment for non-squamous lung cancer without a driver mutation","route":"/key-papers/paper-keynote-189-nejm-2018/"},{"id":"paper-sandler-ecog-4599-bevacizumab-nsclc-nejm-2006","kind":"paper","name":"Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer","route":"/key-papers/paper-sandler-ecog-4599-bevacizumab-nsclc-nejm-2006/"}],"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/"},{"id":"lung-squamous-cell-carcinoma","kind":"cancer","name":"Squamous cell carcinoma of the lung","route":"/cancers/lung-squamous-cell-carcinoma/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"}],"drug":[{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"gemcitabine","kind":"drug","name":"Gemcitabine","route":"/drugs/gemcitabine/"},{"id":"pemetrexed","kind":"drug","name":"Pemetrexed","route":"/drugs/pemetrexed/"}],"term":[{"id":"histology","kind":"term","name":"Histology","route":"/terms/histology/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-dose-optimisation","kind":"bottleneck","name":"Wrong doses","route":"/bottlenecks/b-dose-optimisation/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}]}}