Frontiers in immunology · 2026
Oral mucositis risk with EGFR tyrosine kinase inhibitor monotherapies and combination regimens in non-small cell lung cancer: a systematic review and network meta-analysis.
СтатьяСистематический обзорNetwork Meta-AnalysisНазвание и аннотация: Перевод пока не подготовлен
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Sun Huiwen, Yao Yifan, Liu Xinyu, Qiu Ruiyi, Chen Jinhan, Zhang Gaochenxi, Shu Qijin
Аннотация
INTRODUCTION AND AIMS: Oral mucositis (OM) impairs quality of life, necessitates dose modification, and disrupts treatment continuity in patients receiving EGFR tyrosine kinase inhibitors (EGFR-TKIs), yet comparative OM risks across monotherapies and combination regimens remain poorly defined.
METHODS: PubMed, Embase, Web of Science, the Cochrane Library, and ClinicalTrials.gov were searched from inception to June 13, 2026, for phase II or III randomized controlled trials. Bayesian random-effects network meta-analyses estimated odds ratios (ORs) with 95% credible intervals (CrIs) for any-grade and grade ≥3 OM. Treatments were ranked using the surface under the cumulative ranking curve (SUCRA).
RESULTS: Sixty-three trials involving 21,845 participants were included. Compared with chemotherapy, higher odds of any-grade OM were observed with afatinib plus cetuximab (OR 11.97, 95% CrI 2.27-65.45), afatinib (OR 9.73, 95% CrI 3.75-26.50), dacomitinib (OR 5.12, 95% CrI 1.71-16.00), and erlotinib plus chemotherapy (OR 2.84, 95% CrI 1.27-6.53), with low-, high-, moderate-, and very-low-certainty evidence, respectively; for grade ≥3 OM, with afatinib plus cetuximab (OR 13.91, 95% CrI 1.55-199.26), afatinib (OR 8.80, 95% CrI 1.37-100.11), and mobocertinib (OR 8.12, 95% CrI 1.14-97.77), all supported by moderate-certainty evidence. Afatinib plus cetuximab ranked highest for both outcomes (SUCRA, 89.0% and 91.6%). Second-generation EGFR-TKIs generally ranked higher, whereas the third-generation agents osimertinib and furmonertinib ranked lower. Combination regimens often yielded higher point estimates than matched monotherapies, but most comparisons were inconclusive.
CONCLUSIONS: OM risk varies substantially across EGFR-TKI regimens. Higher-risk regimens warrant strengthened baseline oral assessment, patient education, and monitoring during treatment. Given limited head-to-head evidence for novel agents/combinations and imprecision in some estimates, findings warrant further validation in standardized prospective studies.
SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261449930, identifier CRD420261449930.
METHODS: PubMed, Embase, Web of Science, the Cochrane Library, and ClinicalTrials.gov were searched from inception to June 13, 2026, for phase II or III randomized controlled trials. Bayesian random-effects network meta-analyses estimated odds ratios (ORs) with 95% credible intervals (CrIs) for any-grade and grade ≥3 OM. Treatments were ranked using the surface under the cumulative ranking curve (SUCRA).
RESULTS: Sixty-three trials involving 21,845 participants were included. Compared with chemotherapy, higher odds of any-grade OM were observed with afatinib plus cetuximab (OR 11.97, 95% CrI 2.27-65.45), afatinib (OR 9.73, 95% CrI 3.75-26.50), dacomitinib (OR 5.12, 95% CrI 1.71-16.00), and erlotinib plus chemotherapy (OR 2.84, 95% CrI 1.27-6.53), with low-, high-, moderate-, and very-low-certainty evidence, respectively; for grade ≥3 OM, with afatinib plus cetuximab (OR 13.91, 95% CrI 1.55-199.26), afatinib (OR 8.80, 95% CrI 1.37-100.11), and mobocertinib (OR 8.12, 95% CrI 1.14-97.77), all supported by moderate-certainty evidence. Afatinib plus cetuximab ranked highest for both outcomes (SUCRA, 89.0% and 91.6%). Second-generation EGFR-TKIs generally ranked higher, whereas the third-generation agents osimertinib and furmonertinib ranked lower. Combination regimens often yielded higher point estimates than matched monotherapies, but most comparisons were inconclusive.
CONCLUSIONS: OM risk varies substantially across EGFR-TKI regimens. Higher-risk regimens warrant strengthened baseline oral assessment, patient education, and monitoring during treatment. Given limited head-to-head evidence for novel agents/combinations and imprecision in some estimates, findings warrant further validation in standardized prospective studies.
SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261449930, identifier CRD420261449930.