{"entity":{"id":"paper-marcoux-egfr-small-cell-transformation-outcomes-jco-2019","kind":"paper","name":"EGFR-mutant adenocarcinomas that transform to small-cell lung cancer and other neuroendocrine carcinomas: clinical outcomes","aka":[],"tldr":"Sixty-seven patients whose lung cancer changed into small-cell carcinoma were followed across eight hospitals. The change came about a year and a half after diagnosis, chemotherapy worked well and immunotherapy did not work at all.","summary":"Patients with EGFR-mutant small-cell lung cancer and other high-grade neuroendocrine carcinomas were identified retrospectively at eight institutions. Sixty-seven patients were included, with exon 19 deletion in 69%, L858R in 25% and other mutations in 6%. At initial diagnosis 58 had non-small-cell lung cancer and nine had small-cell or mixed histology; all but those nine received one or more EGFR inhibitors before transformation. Median time to transformation was 17.8 months. After transformation, platinum and etoposide and taxanes yielded high response rates, but none of 17 patients who received immunotherapy responded. Median overall survival since diagnosis was 31.5 months and since transformation 10.9 months. Of 59 patients genotyped at transformation, all maintained their founder EGFR mutation and 15 of 19 previously T790M-positive cases were T790 wild-type. Other recurrent mutations included TP53, RB1 and PIK3CA, and central nervous system metastases were frequent after transformation.","asOf":"2026-09-25","links":[{"label":"Marcoux et al., J Clin Oncol 2019: clinical outcomes of 67 EGFR-mutant adenocarcinomas that transformed to small-cell carcinoma","url":"https://doi.org/10.1200/JCO.18.01585"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30550363/"}],"tags":[],"related":["egfr-t790m","egfr-exon-19-deletion","egfr-l858r"],"cancers":["nsclc","sclc"],"sections":[],"technologies":["checkpoint-inhibitor","cgp"],"targets":["egfr","rb1","tp53","pik3ca"],"drugs":[],"companies":[],"institutions":["mgh","yale-cancer-center","mskcc"],"pathways":["lineage-plasticity-neuroendocrine","resistance-routes-map"],"terms":["histologic-transformation","resistance","brain-metastases"],"trials":[],"people":["lecia-sequist"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2019,"doi":"10.1200/JCO.18.01585","pmid":"30550363","authors":"Marcoux N, Gettinger SN, O'Kane G, et al.","paperType":"observational","findings":["Median time from diagnosis to transformation 17.8 months; median survival after transformation 10.9 months.","Platinum and etoposide and taxanes produced high response rates.","No responses to immunotherapy in 17 treated patients.","All transformed tumours kept the founder EGFR mutation and most had lost T790M."],"whatItMeans":"It is the practical guide to what to do after transformation: treat it as small-cell lung cancer with platinum and etoposide, expect central nervous system disease, and do not expect a checkpoint inhibitor to help.","caveats":["Retrospective across eight institutions with varying practice.","Sixty-seven patients, and transformation is diagnosed only where rebiopsy was performed.","Treatment was not randomised."],"changedPractice":false,"participants":67},"route":"/key-papers/paper-marcoux-egfr-small-cell-transformation-outcomes-jco-2019/","neighbours":{"biomarker":[{"id":"egfr-exon-19-deletion","kind":"biomarker","name":"EGFR exon 19 deletion","route":"/biomarkers/egfr-exon-19-deletion/"},{"id":"egfr-l858r","kind":"biomarker","name":"EGFR L858R","route":"/biomarkers/egfr-l858r/"},{"id":"egfr-t790m","kind":"biomarker","name":"EGFR T790M","route":"/biomarkers/egfr-t790m/"}],"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"sclc","kind":"cancer","name":"Small-cell lung cancer","route":"/cancers/sclc/"}],"technology":[{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"pik3ca","kind":"target","name":"PIK3CA / PI3K-alpha","route":"/targets/pik3ca/"},{"id":"rb1","kind":"target","name":"RB1","route":"/targets/rb1/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"institution":[{"id":"mgh","kind":"institution","name":"Massachusetts General Hospital Cancer Center","route":"/institutions/mgh/"},{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"},{"id":"yale-cancer-center","kind":"institution","name":"Yale Cancer Center / Smilow Cancer Hospital","route":"/institutions/yale-cancer-center/"}],"pathway":[{"id":"lineage-plasticity-neuroendocrine","kind":"pathway","name":"Lineage plasticity & neuroendocrine transformation","route":"/pathways/lineage-plasticity-neuroendocrine/"},{"id":"resistance-routes-map","kind":"pathway","name":"Resistance routes: how a blocked pathway comes back","route":"/pathways/resistance-routes-map/"}],"term":[{"id":"brain-metastases","kind":"term","name":"Brain metastases (intracranial disease)","route":"/terms/brain-metastases/"},{"id":"resistance","kind":"term","name":"Drug resistance (primary and acquired)","route":"/terms/resistance/"},{"id":"histologic-transformation","kind":"term","name":"Histologic transformation","route":"/terms/histologic-transformation/"}],"person":[{"id":"lecia-sequist","kind":"person","name":"Lecia V. Sequist","route":"/people/lecia-sequist/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}]}}