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Contemporary chemotherapy outcomes specific to AGAs are lacking despite growing reliance on single-arm studies and external-control analyses. We sought to establish first-line platinum-doublet chemotherapy outcomes in advanced NSCLC with AGAs using data from RCTs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We extracted objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) data from Phase 2\/3 RCTs. Individual patient-level data were reconstructed from Kaplan\u2013Meier curves to pool and compare PFS and OS across AGAs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty-two RCTs (\n                      <jats:italic>n\u2009<\/jats:italic>\n                      =\u20092132) were included. Across most AGAs, platinum-doublet chemotherapy produced similar outcomes-pooled ORRs ranging from 28.7 to 39.0% and median PFS from 6.0 to 7.3\u00a0months. Pairwise comparisons showed better ORR\/PFS for\n                      <jats:italic>RET<\/jats:italic>\n                      fusion (one trial with control arm-chemotherapy\/pembrolizumab) and shorter OS for\n                      <jats:italic>KRAS<\/jats:italic>\n                      mutation versus other AGAs (logrank\n                      <jats:italic>P<\/jats:italic>\n                      &lt;.001). Detailed pooled ORR and median PFS and OS were:\n                      <jats:italic>ALK<\/jats:italic>\n                      rearrangement (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0461)\u2014ORR 39.0% (95% CI 25.8\u201352.2), PFS 7.0\u00a0months (6.8\u20137.2), OS 43.0\u00a0months (32.2-inestimable); common\n                      <jats:italic>EGFR<\/jats:italic>\n                      mutation (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a01038)\u2014ORR 28.7% (22.3\u201335.1), PFS 6.0\u00a0months (5.7\u20136.3), OS 27.4\u00a0months (26.1\u201329.3); uncommon\n                      <jats:italic>EGFR<\/jats:italic>\n                      mutation (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a061)\u2014ORR 35.1% (12.6\u201357.7), PFS 6.7\u00a0months (5.2\u20138.4), OS 29.5\u00a0months (13.3\u2014inestimable);\n                      <jats:italic>EGFR<\/jats:italic>\n                      exon 20 insertion (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0330)\u2014ORR 38.3% (21.7\u201355.0), PFS 7.3\u00a0months (6.9\u20138.6), OS 30.1\u00a0months (29.1\u2014inestimable);\n                      <jats:italic>KRAS<\/jats:italic>\n                      mutation (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0140)\u2014ORR 21.7% (12.4\u201330.9), PFS 6.2\u00a0months (4.7\u20136.9), OS 10.8\u00a0months (8.8\u201312.7);\n                      <jats:italic>RET<\/jats:italic>\n                      fusion (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0102)\u2014ORR 65.0% (54.5\u201375.5), PFS 11.4\u00a0months (8.9\u201316.9), OS not available.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Platinum-doublet chemotherapy yields remarkably consistent ORR and PFS across most advanced NSCLC with AGAs. These data provide contemporary molecularly defined benchmarks that may support interpretation of single-arm studies, development of external-control analyses, and future trial design in this rare population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00408-026-00946-3","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T10:52:39Z","timestamp":1791370359000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Contemporary Chemotherapy Benchmarks for Molecularly Defined Advanced NSCLC: Reconstructed Individual Patient-Level Data of 22 Randomized Trials"],"prefix":"10.1007","volume":"204","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5918-4439","authenticated-orcid":false,"given":"Deborah Di-Xin","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Lord","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"John","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert John","family":"Simes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chee Khoon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"issue":"6","key":"946_CR1","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1200\/JCO.21.01626","volume":"40","author":"AC Tan","year":"2022","unstructured":"Tan AC, Tan DS (2022) Targeted therapies for lung cancer patients with oncogenic driver molecular alterations. 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