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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.
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.
The 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.
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.
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.
The ceiling of undirected cytotoxic chemotherapy, measured precisely. Everything that came afterwards, from histology-directed pemetrexed to EGFR inhibitors to checkpoint blockade, is an attempt to break a plateau this trial demonstrated could not be broken by changing the drugs.
Shares Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer, Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs, Cisplatin, Lung cancer (all types) and the tag lung-evidence.
Shares Histology, Adenocarcinoma of the lung, Biomarkers are not validated or standardised, Lung cancer (all types) and the tag lung-evidence.
Shares Histology, Lung cancer (all types), Non-small-cell lung cancer and the tag lung-evidence.
Shares Wrong doses, Biomarkers are not validated or standardised, Lung cancer (all types), Non-small-cell lung cancer and the tag lung-evidence.
Shares Adenocarcinoma of the lung, Biomarkers are not validated or standardised, Lung cancer (all types), Non-small-cell lung cancer and the tag lung-evidence.
Shares Journal of Clinical Oncology, Cisplatin, Lung cancer (all types), Non-small-cell lung cancer and the tag lung-evidence.
Shares Biomarkers are not validated or standardised, Cisplatin, Lung cancer (all types), Non-small-cell lung cancer and the tag lung-evidence.
Shares Adenocarcinoma of the lung, Biomarkers are not validated or standardised, Lung cancer (all types), Non-small-cell lung cancer and the tag lung-evidence.