{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T05:52:15Z","timestamp":1791525135061,"version":"4.3.4"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Comparative evidence regarding the efficacy and safety of almonertinib in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) remains fragmented across randomized and real-world studies. We conducted a systematic review and meta-analysis to comprehensively evaluate the comparative clinical performance of almonertinib.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Eight electronic databases were systematically searched from inception to March 2025. Comparative studies evaluating almonertinib versus active control regimens in patients with EGFR-mutated NSCLC were included. Random-effects meta-analyses were performed to synthesize objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events. Methodological quality was assessed using the Cochrane Risk of Bias tool and analogous domains for observational studies, and certainty of evidence was evaluated using the GRADE framework.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fifteen comparative studies involving 1,902 patients met the eligibility criteria. Compared with control regimens, almonertinib was associated with higher pooled ORR (RR = 1.33, 95% CI 1.08\u20131.65) and DCR (RR = 1.14, 95% CI 1.03\u20131.26). However, after trim-and-fill adjustment for potential publication bias, the 95% CIs for both ORR and DCR included the null value, suggesting that the observed response benefits may be influenced by small-study effects. No statistically significant differences were observed for pooled PFS or OS. Almonertinib demonstrated a generally favorable safety profile, with a lower incidence of diarrhea, while rates of grade \u22653 adverse events and other major toxicities were broadly comparable between groups. Integrated analyses further suggested consistent concordance between ORR and DCR across most studies, supporting improved short-term disease control despite moderate-to-substantial between-study heterogeneity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Current comparative evidence suggests that almonertinib may improve tumor response and disease control while maintaining a favorable tolerability profile in patients with EGFR-mutated NSCLC. Although favorable objective response outcomes were observed, these benefits may be influenced by small-study effects, and definitive survival advantages remain uncertain. These findings support almonertinib as a clinically meaningful therapeutic option, while underscoring the need for cautious interpretation and for larger, high-quality comparative trials with longer follow-up to further define its long-term clinical value.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/doi.org\/10.17605\/OSF.IO\/ZDF2N<\/jats:ext-link>\n                      ; Identifier: OSF.IO\/ZDF2N.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1932051","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T05:35:25Z","timestamp":1791524125000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative effectiveness and safety of almonertinib in EGFR-mutated non-small cell lung cancer: an integrated evidence synthesis"],"prefix":"10.3389","volume":"17","author":[{"given":"Biaoxue","family":"Rong","sequence":"first","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of Xi\u2019an Medical University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Gansu Provincial Hospital","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Jining First People\u2019s Hospital","place":["Jining, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of Xi\u2019an Medical University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of Xi\u2019an Medical University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of Xi\u2019an Medical University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of Xi\u2019an Medical University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"146","DOI":"10.3390\/curroncol32030146","article-title":"Lung cancer: targeted therapy in 2025","volume":"32","author":"Bouchard","year":"2025","journal-title":"Curr. 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