{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:01:13Z","timestamp":1791284473665,"version":"4.1.0"},"reference-count":22,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"4","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Preclinical studies demonstrated that dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways delay the emergence of resistance to EGFR tyrosine kinase inhibitors (TKIs), and in trials with first-generation EGFR TKIs, the combination of EGFR VEGF pathway inhibitors prolonged progression-free survival (PFS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      The RAMOSE trial (ClinicalTrials.gov identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT03909334\">NCT03909334<\/jats:ext-link>\n                      , HCRN LUN-18-335) is a randomized, open-label multicenter phase II study comparing osimertinib with ramucirumab (arm A) to osimertinib (arm B) for initial treatment of metastatic\n                      <jats:italic>EGFR<\/jats:italic>\n                      -mutant non\u2013small cell lung cancer (NSCLC) with 2:1 random assignment. The primary end point is PFS for evaluable patients; secondary end points include objective response rates (ORRs), disease control rate (DCR), overall survival, and safety. The stratification criteria were\n                      <jats:italic>EGFR<\/jats:italic>\n                      mutation type and the presence of CNS metastasis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      At data cutoff on August 29, 2023, 160 patients consented, 147 patients received treatment, and 139 patients were evaluable with at least one scan. In this preplanned interim analysis, the median follow-up was 16.6 months. Among the evaluable patients, 57 PFS events occurred. The median PFS was 24.8 (A) versus 15.6 (B) months (hazard ratio, 0.55 [95% CI, 0.32 to 0.93]; log-rank\n                      <jats:italic>P<\/jats:italic>\n                      = .023), 12-month PFS rate was 76.7% (A) versus 61.9% (B;\n                      <jats:italic>P<\/jats:italic>\n                      = .026). No significant difference was observed in the ORRs and DCRs between arms. Any-grade (G) adverse events (AEs) occurred in 100% (A) and 98% (B) of patients, with no G5 treatment-related AE (TRAE), one G4 TRAE (hyponatremia, A), and 53% (A) versus 41% (B) G3 TRAEs. AE-related discontinuation occurred in 13 patients (9.7% in A and 8.7% in B). The safety profile was in line with known safety of each drug.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      Ramucirumab plus osimertinib significantly prolonged PFS compared with osimertinib alone in patients with TKI-na\u00efve\n                      <jats:italic>EGFR<\/jats:italic>\n                      -mutant NSCLC. The combination is safe and well tolerated.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.24.00533","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T15:59:26Z","timestamp":1728403166000},"page":"403-411","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":57,"title":["A Multicenter Open-Label Randomized Phase II Study of Osimertinib With and Without Ramucirumab in Tyrosine Kinase Inhibitor\u2013Na\u00efve\n                    <i>EGFR<\/i>\n                    -Mutant Metastatic Non\u2013Small Cell Lung Cancer (RAMOSE trial)"],"prefix":"10.1200","volume":"43","clinical-trial-number":[{"clinical-trial-number":"nct03909334","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8554-1185","authenticated-orcid":true,"given":"Xiuning","family":"Le","sequence":"first","affiliation":[{"name":"UT MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7550-2094","authenticated-orcid":true,"given":"Jyoti D.","family":"Patel","sequence":"additional","affiliation":[{"name":"Northwestern University, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0390-5716","authenticated-orcid":true,"given":"Elaine","family":"Shum","sequence":"additional","affiliation":[{"name":"New York University Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Baik","sequence":"additional","affiliation":[{"name":"University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0542-6054","authenticated-orcid":true,"given":"Rachel E.","family":"Sanborn","sequence":"additional","affiliation":[{"name":"Earle A. 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