{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:17:35Z","timestamp":1791389855138,"version":"4.3.3"},"reference-count":36,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n \n Use of tyrosine kinase inhibitors (TKIs) is the standard therapy for epidermal growth factor receptor (\n EGFR<\/jats:italic>\n )\u2013mutated non\u2013small cell lung cancer (NSCLC) with brain metastases. Several studies have shown that adding chemotherapy to EGFR-TKIs could improve progression-free survival (PFS) in patients with\n EGFR<\/jats:italic>\n -mutant advanced NSCLC; however, the efficacy of these agents in patients with brain metastases remains unclear.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To investigate the efficacy and safety of gefitinib plus chemotherapy (pemetrexed with platinum) compared with gefitinib alone in patients with untreated\n EGFR-<\/jats:italic>\n mutant NSCLC brain metastases.\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n \n This open-label prospective, multicenter, phase 3 randomized clinical trial was conducted in 6 centers in China from January 13, 2016, to August 27, 2021. The median follow-up time was 21.1 months (IQR, 13.5-31.8 months). Patients with untreated confirmed brain metastases and\n EGFR<\/jats:italic>\n -sensitive mutated NSCLC were enrolled.\n <\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n The eligible patients were randomly assigned (1:1) to receive gefitinib plus chemotherapy or gefitinib alone.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary end point was intracranial PFS; secondary end points included PFS, overall survival (OS), intracranial objective response rate, overall objective response rate, and safety. Intention-to-treat analysis was performed.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 161 patients (87 [54.0%] women; mean [SD] age, 55 [9.8] years; range, 26-80 years) were enrolled and randomized to receive gefitinib (n\u2009=\u200981) or gefitinib plus chemotherapy (n\u2009=\u200980). The median intracranial PFS was 15.6 months (95% CI, 14.3-16.9 months) in the gefitinib plus chemotherapy group vs 9.1 months (95% CI, 8.0-10.2 months) in the gefitinib group (hazard ratio, 0.36; 95% CI, 0.25-0.53;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). Similarly, the median PFS was significantly longer with gefitinib plus chemotherapy than gefitinib alone (16.3; 95% CI, 14.4-18.2 months vs 9.5; 95% CI, 8.3-10.8 months;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). Gefitinib plus chemotherapy had a better intracranial objective response rate (85.0%; 95% CI, 77.0%-93.0% vs 63.0%; 95% CI, 52.2%-73.7%;\n P<\/jats:italic>\n \u2009=\u2009.002) and overall objective response rate (80.0%; 95% CI, 71.0%-89.0% vs 64.2%; 95% CI, 53.5%-74.9%;\n P<\/jats:italic>\n \u2009=\u2009.03) than gefitinib alone. At data cutoff, the median OS was also significantly longer in the gefitinib plus chemotherapy group vs the gefitinib group (35.0 vs 28.9 months; hazard ratio, 0.65; 95% CI, 0.43-0.99;\n P<\/jats:italic>\n \u2009=\u2009.04). Grade 3 or worse adverse events were more common with gefitinib plus chemotherapy, most of which were manageable.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n In this randomized clinical trial, gefitinib plus chemotherapy significantly improved intracranial PFS, PFS, and OS compared with gefitinib alone in patients with untreated\n EGFR-<\/jats:italic>\n mutant NSCLC brain metastases and could be an optional first-line treatment for these patients.\n <\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT01951469<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2022.55050","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T11:03:35Z","timestamp":1675854215000},"page":"e2255050","source":"Crossref","is-referenced-by-count":55,"title":["Gefitinib Plus Chemotherapy vs Gefitinib Alone in Untreated\n EGFR<\/i>\n -Mutant Non\u2013Small Cell Lung 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