Non-Cochrane · intervention · PM42827960
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.
Sun Huiwen, Yao Yifan, Liu Xinyu, et al. · Frontiers in immunology · 2026 · PubMed · doi:10.3389/fimmu.2026.1957825
Findings
Population Patients with advanced NSCLC (stage III–IV or recurrent disease)
139 findings
| Afatinib + cetuximab | Chemotherapy | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 13.91 [1.55, 199.26] Moderate Downgraded: risk of bias 42 studies · 15903 participants |
| Afatinib + cetuximab | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Non-exclusively Asian populations | OR 5.44 [0.55, 52.7] GRADE not reported 37 studies · 14901 participants |
| Afatinib + cetuximab | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · First-line treatment | OR 12.57 [5.82, 28.18] GRADE not reported 32 studies · 8668 participants |
| Afatinib + cetuximab | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 11.97 [2.27, 65.45] Low Downgraded: risk of bias, inconsistency 61 studies · 20881 participants |
| Afatinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 9.73 [3.75, 26.5] High 61 studies · 20881 participants |
| Afatinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · First-line treatment | OR 10.49 [6.29, 18.45] GRADE not reported 32 studies · 8668 participants |
| Afatinib | Chemotherapy | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 8.8 [1.37, 100.11] Moderate Downgraded: imprecision 42 studies · 15903 participants |
| Afatinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Second-line or later treatment (≥2L) | OR 3.51 [0.22, 56.72] GRADE not reported 26 studies · 11361 participants |
| Afatinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Non-exclusively Asian populations | OR 4.44 [1, 19.67] GRADE not reported 37 studies · 14901 participants |
| Erlotinib + cabozantinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Non-exclusively Asian populations | OR 5.88 [0.3, 147.75] GRADE not reported 37 studies · 14901 participants |
| Erlotinib + cabozantinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 9.64 [0.81, 150.82] Low Downgraded: risk of bias, imprecision, inconsistency 61 studies · 20881 participants |
| Erlotinib + cabozantinib | Chemotherapy | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 0.35 [0.013, 9.2] Very low Downgraded: risk of bias, imprecision 42 studies · 15903 participants |
| Erlotinib + cabozantinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Second-line or later treatment (≥2L) | OR 3.31 [0.07, 177.12] GRADE not reported 26 studies · 11361 participants |
| Dacomitinib | Chemotherapy | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 1.6 [0.39, 7.5] Very low Downgraded: risk of bias, imprecision 42 studies · 15903 participants |
| Dacomitinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Second-line or later treatment (≥2L) | OR 1.98 [0.18, 21.84] GRADE not reported 26 studies · 11361 participants |
| Dacomitinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 5.12 [1.71, 16] Moderate Downgraded: inconsistency 61 studies · 20881 participants |
| Dacomitinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Non-exclusively Asian populations | OR 2.5 [0.51, 12.46] GRADE not reported 37 studies · 14901 participants |
| Dacomitinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · First-line treatment | OR 7.03 [3.38, 14.88] GRADE not reported 32 studies · 8668 participants |
| Afatinib + bevacizumab | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · First-line treatment | OR 5.87 [1.98, 17.78] GRADE not reported 32 studies · 8668 participants |
| Afatinib + bevacizumab | Chemotherapy | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 12 [0.78, 250] Very low Downgraded: risk of bias, imprecision 42 studies · 15903 participants |
| Afatinib + bevacizumab | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 5.42 [0.6, 50.94] Low Downgraded: risk of bias, imprecision, inconsistency 61 studies · 20881 participants |
| Gefitinib + anlotinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 4.43 [0.55, 36.76] Moderate Downgraded: imprecision, inconsistency 61 studies · 20881 participants |
| Gefitinib + anlotinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · First-line treatment | OR 7.16 [2.65, 21.18] GRADE not reported 32 studies · 8668 participants |
| Gefitinib + anlotinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Exclusively Asian populations | OR 4.74 [0.77, 27.33] GRADE not reported 15 studies · 3559 participants |
| Gefitinib + anlotinib | Chemotherapy | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 0.75 [0.057, 14] Low Downgraded: imprecision 42 studies · 15903 participants |
| Mobocertinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · First-line treatment | OR 4.18 [2.08, 8.5] GRADE not reported 32 studies · 8668 participants |
| Mobocertinib | Chemotherapy | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 8.12 [1.14, 97.77] Moderate Downgraded: imprecision, inconsistency 42 studies · 15903 participants |
| Mobocertinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 4.15 [0.63, 27.43] Low Downgraded: inconsistency 61 studies · 20881 participants |
| Mobocertinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Non-exclusively Asian populations | OR 4.18 [0.37, 46.22] GRADE not reported 37 studies · 14901 participants |
| Afatinib + chemotherapy | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 3.83 [0.37, 52.32] Low Downgraded: imprecision, inconsistency 61 studies · 20881 participants |
| Afatinib + chemotherapy | Chemotherapy | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 8 [0.38, 658] Low Downgraded: imprecision 42 studies · 15903 participants |
| Afatinib + chemotherapy | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Non-exclusively Asian populations | OR 3.87 [0.24, 78.22] GRADE not reported 37 studies · 14901 participants |
| Afatinib + chemotherapy | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Second-line or later treatment (≥2L) | OR 3.86 [0.12, 139.98] GRADE not reported 26 studies · 11361 participants |
| Erlotinib + chemotherapy | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · First-line treatment | OR 3.76 [2.05, 7.22] GRADE not reported 32 studies · 8668 participants |
| Erlotinib + chemotherapy | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Non-exclusively Asian populations | OR 2.09 [0.63, 7.49] GRADE not reported 37 studies · 14901 participants |
| Erlotinib + chemotherapy | Chemotherapy | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 0.53 [0.13, 2.1] Very low Downgraded: risk of bias, imprecision 42 studies · 15903 participants |
| Erlotinib + chemotherapy | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Second-line or later treatment (≥2L) | OR 2.89 [0.34, 27.64] GRADE not reported 26 studies · 11361 participants |
| Erlotinib + chemotherapy | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 2.84 [1.27, 6.53] Very low Downgraded: risk of bias, inconsistency 61 studies · 20881 participants |
| Lazertinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · First-line treatment | OR 4.21 [1.78, 10.34] GRADE not reported 32 studies · 8668 participants |
| Lazertinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Non-exclusively Asian populations | OR 1.04 [0.06, 18.2] GRADE not reported 37 studies · 14901 participants |
| Lazertinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 2.6 [0.35, 19.74] Low Downgraded: imprecision, inconsistency 61 studies · 20881 participants |
| Erlotinib + bevacizumab | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Exclusively Asian populations | OR 6.15 [0.99, 41.67] GRADE not reported 15 studies · 3559 participants |
| Erlotinib + bevacizumab | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · First-line treatment | OR 7.12 [3.03, 18.32] GRADE not reported 32 studies · 8668 participants |
| Erlotinib + bevacizumab | Chemotherapy | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 0.24 [0.048, 1.3] Very low Downgraded: risk of bias, imprecision 42 studies · 15903 participants |
| Erlotinib + bevacizumab | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 2.44 [0.8, 7.76] Low Downgraded: risk of bias, imprecision, inconsistency 61 studies · 20881 participants |
| Erlotinib + bevacizumab | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Non-exclusively Asian populations | OR 1.25 [0.21, 7.86] GRADE not reported 37 studies · 14901 participants |
| Erlotinib + bevacizumab | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Second-line or later treatment (≥2L) | OR 0.74 [0.02, 24.23] GRADE not reported 26 studies · 11361 participants |
| Gefitinib + chemotherapy | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Non-exclusively Asian populations | OR 3.21 [0.25, 43.02] GRADE not reported 37 studies · 14901 participants |
| Gefitinib + chemotherapy | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · First-line treatment | OR 3.18 [1.86, 5.31] GRADE not reported 32 studies · 8668 participants |
| Gefitinib + chemotherapy | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Second-line or later treatment (≥2L) | OR 3.2 [0.12, 85.07] GRADE not reported 26 studies · 11361 participants |
| Gefitinib + chemotherapy | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Exclusively Asian populations | OR 2.75 [0.81, 8.77] GRADE not reported 15 studies · 3559 participants |
| Gefitinib + chemotherapy | Chemotherapy | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 0.97 [0.25, 3.8] Very low Downgraded: risk of bias, imprecision 42 studies · 15903 participants |
| Gefitinib + chemotherapy | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 2.2 [0.83, 5.84] Very low Downgraded: risk of bias, inconsistency 61 studies · 20881 participants |
| Osimertinib + bevacizumab | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Second-line or later treatment (≥2L) | OR 2 [0.03, 125.3] GRADE not reported 26 studies · 11361 participants |
| Osimertinib + bevacizumab | Chemotherapy | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 0.044 [0.00054, 1.5] Very low Downgraded: risk of bias, imprecision 42 studies · 15903 participants |
| Osimertinib + bevacizumab | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Non-exclusively Asian populations | OR 2.26 [0.09, 56.62] GRADE not reported 37 studies · 14901 participants |
| Osimertinib + bevacizumab | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 1.88 [0.23, 15.11] Very low Downgraded: risk of bias, imprecision, inconsistency 61 studies · 20881 participants |
| Erlotinib + sunitinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Non-exclusively Asian populations | OR 1.14 [0.15, 9.37] GRADE not reported 37 studies · 14901 participants |
| Erlotinib + sunitinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 1.88 [0.38, 9.6] Low Downgraded: imprecision, inconsistency 61 studies · 20881 participants |
| Erlotinib + sunitinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Second-line or later treatment (≥2L) | OR 0.64 [0.04, 10.47] GRADE not reported 26 studies · 11361 participants |
| Erlotinib + ramucirumab | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Non-exclusively Asian populations | OR 1.04 [0.08, 14.04] GRADE not reported 37 studies · 14901 participants |
| Erlotinib + ramucirumab | Chemotherapy | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 0.26 [0.037, 1.9] Low Downgraded: imprecision 42 studies · 15903 participants |
| Erlotinib + ramucirumab | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · First-line treatment | OR 4.82 [1.92, 13.12] GRADE not reported 32 studies · 8668 participants |
| Erlotinib + ramucirumab | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 1.75 [0.25, 13.03] Low Downgraded: imprecision, inconsistency 61 studies · 20881 participants |
| Osimertinib + chemotherapy | Chemotherapy | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 0.044 [0.00052, 1.5] Very low Downgraded: risk of bias, imprecision 42 studies · 15903 participants |
| Osimertinib + chemotherapy | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 1.49 [0.29, 7.69] Very low Downgraded: risk of bias, imprecision 61 studies · 20881 participants |
| Osimertinib + chemotherapy | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Non-exclusively Asian populations | OR 1.34 [0.16, 11.41] GRADE not reported 37 studies · 14901 participants |
| Osimertinib + chemotherapy | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Second-line or later treatment (≥2L) | OR 1.62 [0.11, 25.04] GRADE not reported 26 studies · 11361 participants |
| Aumolertinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 1.28 [0.17, 9.72] Low Downgraded: imprecision, inconsistency 61 studies · 20881 participants |
| Aumolertinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Exclusively Asian populations | OR 1.38 [0.24, 7.4] GRADE not reported 15 studies · 3559 participants |
| Aumolertinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · First-line treatment | OR 2.06 [0.87, 4.97] GRADE not reported 32 studies · 8668 participants |
| Erlotinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · First-line treatment | OR 3.95 [1.92, 8.95] GRADE not reported 32 studies · 8668 participants |
| Erlotinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Exclusively Asian populations | OR 2.78 [0.66, 12.94] GRADE not reported 15 studies · 3559 participants |
| Erlotinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 1.41 [0.72, 2.82] Very low Downgraded: risk of bias, imprecision, inconsistency 61 studies · 20881 participants |
| Erlotinib | Chemotherapy | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 0.22 [0.082, 0.65] Very low Downgraded: risk of bias, imprecision 42 studies · 15903 participants |
| Erlotinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Non-exclusively Asian populations | OR 0.85 [0.32, 2.39] GRADE not reported 37 studies · 14901 participants |
| Erlotinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Second-line or later treatment (≥2L) | OR 0.48 [0.1, 2.3] GRADE not reported 26 studies · 11361 participants |
| Gefitinib | Chemotherapy | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 0.19 [0.055, 0.61] Very low Downgraded: risk of bias, imprecision 42 studies · 15903 participants |
| Gefitinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · First-line treatment | OR 1.95 [1.34, 2.87] GRADE not reported 32 studies · 8668 participants |
| Gefitinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Second-line or later treatment (≥2L) | OR 0.56 [0.12, 2.53] GRADE not reported 26 studies · 11361 participants |
| Gefitinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Non-exclusively Asian populations | OR 0.48 [0.1, 2.2] GRADE not reported 37 studies · 14901 participants |
| Gefitinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Exclusively Asian populations | OR 1.3 [0.61, 2.54] GRADE not reported 15 studies · 3559 participants |
| Gefitinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 1.21 [0.64, 2.29] Very low Downgraded: risk of bias, imprecision 61 studies · 20881 participants |
| Gefitinib + nimotuzumab | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Exclusively Asian populations | OR 1.06 [0.18, 5.92] GRADE not reported 15 studies · 3559 participants |
| Gefitinib + nimotuzumab | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Second-line or later treatment (≥2L) | OR 0.46 [0.01, 15.3] GRADE not reported 26 studies · 11361 participants |
| Gefitinib + nimotuzumab | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 0.99 [0.13, 7.8] Very low Downgraded: risk of bias, imprecision, inconsistency 61 studies · 20881 participants |
| Osimertinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Non-exclusively Asian populations | OR 0.93 [0.12, 7.01] GRADE not reported 37 studies · 14901 participants |
| Osimertinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Second-line or later treatment (≥2L) | OR 0.81 [0.06, 11.13] GRADE not reported 26 studies · 11361 participants |
| Osimertinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 0.87 [0.18, 4.12] Very low Downgraded: risk of bias, imprecision 61 studies · 20881 participants |
| Osimertinib | Chemotherapy | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 0.051 [0.00092, 0.88] Very low Downgraded: risk of bias, imprecision 42 studies · 15903 participants |
| Furmonertinib | Chemotherapy | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 0.15 [0.0065, 3.7] Low Downgraded: imprecision 42 studies · 15903 participants |
| Furmonertinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · First-line treatment | OR 1.1 [0.39, 2.95] GRADE not reported 32 studies · 8668 participants |
| Furmonertinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Exclusively Asian populations | OR 0.72 [0.11, 4.05] GRADE not reported 15 studies · 3559 participants |
| Furmonertinib | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 0.67 [0.08, 5.44] Very low Downgraded: risk of bias, imprecision, inconsistency 61 studies · 20881 participants |
| Placebo | Chemotherapy | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 0.04 [0.0042, 0.24] Moderate Downgraded: imprecision 42 studies · 15903 participants |
| Placebo | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Second-line or later treatment (≥2L) | OR 0.1 [0.01, 1.09] GRADE not reported 26 studies · 11361 participants |
| Placebo | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) · Non-exclusively Asian populations | OR 0.09 [0.01, 0.53] GRADE not reported 37 studies · 14901 participants |
| Placebo | Chemotherapy | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 0.25 [0.07, 0.94] Low Downgraded: inconsistency 61 studies · 20881 participants |
| Afatinib | Erlotinib | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 39 [6.3, 434] High 42 studies · 15903 participants |
| Afatinib | Erlotinib | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 6.94 [2.42, 20.04] High 61 studies · 20881 participants |
| Afatinib | Gefitinib | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 46 [6.8, 575] Moderate Downgraded: risk of bias 42 studies · 15903 participants |
| Afatinib | Gefitinib | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 8.06 [2.95, 22.91] Moderate Downgraded: risk of bias 61 studies · 20881 participants |
| Afatinib | Osimertinib | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 11.19 [1.81, 71.61] Low Downgraded: risk of bias, inconsistency 61 studies · 20881 participants |
| Afatinib | Osimertinib | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 191 [5.4, 17406] Moderate Downgraded: risk of bias 42 studies · 15903 participants |
| Afatinib | Furmonertinib | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 60 [1.7, 2661] Moderate Downgraded: imprecision 42 studies · 15903 participants |
| Afatinib | Furmonertinib | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 14.52 [1.58, 139.13] Low Downgraded: risk of bias, inconsistency 61 studies · 20881 participants |
| Dacomitinib | Erlotinib | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 7 [2, 27] High 42 studies · 15903 participants |
| Dacomitinib | Erlotinib | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 3.65 [1.26, 10.59] Moderate Downgraded: inconsistency 61 studies · 20881 participants |
| Dacomitinib | Gefitinib | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 8.1 [2.1, 43] High 42 studies · 15903 participants |
| Dacomitinib | Gefitinib | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 4.24 [1.4, 13.25] Low Downgraded: inconsistency 61 studies · 20881 participants |
| Erlotinib + cabozantinib | Erlotinib | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 1.6 [0.07, 34] Very low Downgraded: risk of bias, imprecision 42 studies · 15903 participants |
| Erlotinib + cabozantinib | Erlotinib | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 6.83 [0.62, 97.68] Very low Downgraded: risk of bias, imprecision, inconsistency 61 studies · 20881 participants |
| Erlotinib + chemotherapy | Erlotinib | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 2.4 [0.59, 9.4] Very low Downgraded: risk of bias, imprecision 42 studies · 15903 participants |
| Erlotinib + chemotherapy | Erlotinib | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 2.02 [0.84, 4.79] Very low Downgraded: risk of bias, inconsistency 61 studies · 20881 participants |
| Erlotinib + bevacizumab | Erlotinib | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 1.1 [0.3, 3.8] Low Downgraded: imprecision 42 studies · 15903 participants |
| Erlotinib + bevacizumab | Erlotinib | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 1.74 [0.7, 4.33] Moderate Downgraded: imprecision, inconsistency 61 studies · 20881 participants |
| Erlotinib + sunitinib | Erlotinib | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 1.34 [0.31, 5.82] Low Downgraded: imprecision, inconsistency 61 studies · 20881 participants |
| Erlotinib + ramucirumab | Erlotinib | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 1.1 [0.21, 6.2] Moderate Downgraded: imprecision 42 studies · 15903 participants |
| Erlotinib + ramucirumab | Erlotinib | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 1.25 [0.2, 8.03] Low Downgraded: imprecision, inconsistency 61 studies · 20881 participants |
| Gefitinib + anlotinib | Gefitinib | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 3.9 [0.42, 55] Low Downgraded: imprecision 42 studies · 15903 participants |
| Gefitinib + anlotinib | Gefitinib | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 3.67 [0.5, 27.45] Low Downgraded: imprecision, inconsistency 61 studies · 20881 participants |
| Gefitinib + chemotherapy | Gefitinib | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 1.82 [0.72, 4.55] Low Downgraded: risk of bias, imprecision, inconsistency 61 studies · 20881 participants |
| Gefitinib + chemotherapy | Gefitinib | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 5.1 [1.2, 25] Low Downgraded: risk of bias, imprecision 42 studies · 15903 participants |
| Gefitinib + nimotuzumab | Gefitinib | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 0.82 [0.12, 5.81] Very low Downgraded: risk of bias, imprecision, inconsistency 61 studies · 20881 participants |
| Osimertinib + bevacizumab | Osimertinib | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 0.91 [0.11, 6.6] Low Downgraded: imprecision 42 studies · 15903 participants |
| Osimertinib + bevacizumab | Osimertinib | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 2.15 [0.54, 8.7] Low Downgraded: imprecision, inconsistency 61 studies · 20881 participants |
| Osimertinib + chemotherapy | Osimertinib | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 1.71 [0.48, 6.07] Very low Downgraded: risk of bias, imprecision 61 studies · 20881 participants |
| Osimertinib + chemotherapy | Osimertinib | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 0.89 [0.11, 6.5] Very low Downgraded: risk of bias, imprecision 42 studies · 15903 participants |
| Afatinib + cetuximab | Afatinib | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 1.23 [0.31, 4.8] Very low Downgraded: risk of bias, imprecision, inconsistency 61 studies · 20881 participants |
| Afatinib + cetuximab | Afatinib | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 1.6 [0.5, 5] Very low Downgraded: risk of bias, imprecision 42 studies · 15903 participants |
| Afatinib + bevacizumab | Afatinib | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 0.56 [0.08, 4.07] Very low Downgraded: risk of bias, imprecision, inconsistency 61 studies · 20881 participants |
| Afatinib + bevacizumab | Afatinib | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 1.3 [0.19, 9.2] Very low Downgraded: risk of bias, imprecision 42 studies · 15903 participants |
| Afatinib + chemotherapy | Afatinib | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 0.91 [0.019, 97] Low Downgraded: imprecision 42 studies · 15903 participants |
| Afatinib + chemotherapy | Afatinib | Any-grade oral mucositis Oncology clinical trials (multinational) | OR 0.39 [0.03, 6.26] Low Downgraded: imprecision, inconsistency 61 studies · 20881 participants |
| Mobocertinib | Erlotinib | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 37 [3.7, 533] Moderate Downgraded: inconsistency 42 studies · 15903 participants |
| Mobocertinib | Gefitinib | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 44 [4.3, 673] High 42 studies · 15903 participants |
| Mobocertinib | Osimertinib | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 174 [4.9, 16682] Moderate Downgraded: risk of bias 42 studies · 15903 participants |
| Mobocertinib | Furmonertinib | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 55 [1.3, 2893] Moderate Downgraded: inconsistency 42 studies · 15903 participants |
| Dacomitinib | Osimertinib | Grade ≥3 oral mucositis Oncology clinical trials (multinational) | OR 32 [1.3, 2316] Low Downgraded: risk of bias, inconsistency 42 studies · 15903 participants |
Included primary studies 64
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| AENEAS, 2022 (Lu et al.) NCT:03849768 | NR | this review only | not stated | not extracted yet |
| ARCHER 1009, 2014 (Ramalingam et al.) NCT:01360554 | NR | this review only | not stated | not extracted yet |
| ARCHER 1050, 2017 (Wu et al.) NCT:01774721 | NR | this review only | not stated | not extracted yet |
| AURA3, 2017 (Mok et al.) NCT:02151981 | NR | this review only | not stated | not extracted yet |
| BeTa, 2011 (Herbst et al.) NCT:00130728 | NR | this review only | not stated | not extracted yet |
| BEVERLY, 2022 (Piccirillo et al.) NCT:02633189 | NR | this review only | not stated | not extracted yet |
| BOOSTER, 2022 (Soo et al.) NCT:03133546 | NR | this review only | not stated | not extracted yet |
| Cheng et al., 2016 NCT:01469000 | NR | this review only | not stated | not extracted yet |
| COMPEL, 2025 (Peled et al.) NCT:04765059 | NR | this review only | not stated | not extracted yet |
| Dittrich et al., 2014 NCT:00447057 | NR | this review only | not stated | not extracted yet |
| ECOG-ACRIN 1512, 2017 (Neal et al.) NCT:01708954 | NR | this review only | not stated | not extracted yet |
| ENSURE, 2015 (Wu et al.) NCT:01342965 | NR | this review only | not stated | not extracted yet |
| EXCLAIM-2, 2025 (Jänne et al.) NCT:04129502 | NR | this review only | not stated | not extracted yet |
| FAST-ACT, 2009 (Mok et al.) matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| FASTACT-2, 2013 (Wu et al.) NCT:00883779 | NR | this review only | not stated | not extracted yet |
| FL-ALTER, 2024 (Zhou et al.) NCT:04028778 | NR | this review only | not stated | not extracted yet |
| FLAURA2, 2023 (Planchard et al.) NCT:04035486 | NR | this review only | not stated | not extracted yet |
| FURLONG, 2022 (Shi et al.) NCT:03787992 | NR | this review only | not stated | not extracted yet |
| Groen et al., 2013 NCT:00265317 | NR | this review only | not stated | not extracted yet |
| IFCT-1503 ACE-Lung, 2021 (Cortot et al.) NCT:02716311 | NR | this review only | not stated | not extracted yet |
| IMPRESS, 2015 (Soria et al.) NCT:01544179 | NR | this review only | not stated | not extracted yet |
| INTEREST, 2008 (Kim et al.) NCT:00076388 | NR | this review only | not stated | not extracted yet |
| IPASS, 2009 (Mok et al.) NCT:00322452 | NR | this review only | not stated | not extracted yet |
| ISEL, 2005 (Thatcher et al.) NCT:00242801 | NR | this review only | not stated | not extracted yet |
| ISTANA, 2010 (Lee et al.) matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| KCSG LU12-01, 2017 (Kim et al.) NCT:01498562 | NR | this review only | not stated | not extracted yet |
| Kim et al., 2016 NCT:01783834 | NR | this review only | not stated | not extracted yet |
| LASER301, 2023 (Cho et al.) NCT:04248829 | NR | this review only | not stated | not extracted yet |
| Lee et al., 2023 NCT:03126799 | NR | this review only | not stated | not extracted yet |
| Lilenbaum et al., 2008 NCT:00085839 | NR | this review only | not stated | not extracted yet |
| LOGIK1604/NEJ032A, TAKUMI, 2021 (Tanaka et al.) matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| LUX-Lung 5, 2016 (Schuler et al.) NCT:01085136 | NR | this review only | not stated | not extracted yet |
| LUX-Lung 6, 2014 (Wu et al.) NCT:01121393 | NR | this review only | not stated | not extracted yet |
| LUX-Lung 7, 2017 (Paz-Ares et al.) NCT:01466660 | NR | this review only | not stated | not extracted yet |
| LUX-Lung 8, 2015 (Soria et al.) NCT:01523587 | NR | this review only | not stated | not extracted yet |
| LUX‑Lung 1, 2012 (Mille et al.) NCT:00656136 | NR | this review only | not stated | not extracted yet |
| LUX‑Lung 3, 2023 (Sequist et al.) NCT:00949650 | NR | this review only | not stated | not extracted yet |
| NCIC CTG BR.26, 2014 (Ellis et al.) NCT:01000025 | NR | this review only | not stated | not extracted yet |
| NEJ002, 2010 (Maemondo et al.) matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| NEJ002, 2010 (Maemondo et al.) PMID:0022010 | NR | this review only | not stated | not extracted yet |
| NEJ009, 2020 (Hosomi et al.) PMID:0092020 | NR | this review only | not stated | not extracted yet |
| NEJ026, 2019 (Saito et al.) matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| NEJ026, 2019 (Saito et al.) PMID:0262019 | NR | this review only | not stated | not extracted yet |
| Ninomiya et al., 2023 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| OPTIMAL,CTONG-0802, 2011 (Zhou et al.) NCT:00874419 | NR | this review only | not stated | not extracted yet |
| PDX‑012, 2012 (Kelly et al.) NCT:00606502 | NR | this review only | not stated | not extracted yet |
| Ramalingam et al., 2012 NCT:00769067 | NR | this review only | not stated | not extracted yet |
| Registry study, 2009 NCT:00294762 | NR | this review only | not stated | not extracted yet |
| Registry study, 2010 NCT:01196078 | NR | this review only | not stated | not extracted yet |
| Registry study, 2011 NCT:01998919 | NR | this review only | not stated | not extracted yet |
| Registry study, 2015 NCT:01652469 | NR | this review only | not stated | not extracted yet |
| Registry study, 2017 NCT:00126581 | NR | this review only | not stated | not extracted yet |
| RELAY, 2019 (Nakagawa et al.) NCT:02411448 | NR | this review only | not stated | not extracted yet |
| S103, 2013 (Lee et al.) NCT:00550173 | NR | this review only | not stated | not extracted yet |
| Stinchcomb et al., 2019 NCT:01532089 | NR | this review only | not stated | not extracted yet |
| SUN1087, 2012 (Scagliotti et al.) NCT:00457392 | NR | this review only | not stated | not extracted yet |
| SWOG S1403, 2020 (Goldberg et al.) NCT:02438722 | NR | this review only | not stated | not extracted yet |
| TITAN, 2012 (Ciuleanu et al.) NCT:00556322 | NR | this review only | not stated | not extracted yet |
| TOPICAL, 2012 (Lee et al.) matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| V-15-32, 2008 (Maruyama et al.) NCT:00252707 | NR | this review only | not stated | not extracted yet |
| WJOG9717L, 2022 (Kenmots et al.) PMID:97172022 | NR | this review only | not stated | not extracted yet |
| WJTOG3405, 2010 (Mitsudomi et al.) Breast ductal carcinoma in situ with micro-invasion versus ductal carcinoma in situ: a comparative analysis of clinicopathological and… PMID:34052010 | 2021 | this review only | not stated | not extracted yet |
| Yang et al., 2014 NCT:01017874 | NR | this review only | not stated | not extracted yet |
| Yu et al., 2014 NCT:01769066 | NR | this review only | not stated | not extracted yet |
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Patients with pathologically or cytologically confirmed advanced NSCLC (stage III–IV or recurrent disease) | 63 RCTs, 21,845 randomized participants with advanced, metastatic or recurrent NSCLC (36 first-line, 26 second-line or later, 1 not specified; 26 exclusively Asian) (n=63) |
| Intervention | EGFR-TKI monotherapy (gefitinib, erlotinib, afatinib, dacomitinib, osimertinib, furmonertinib, aumolertinib, lazertinib, mobocertinib), including with matched placebo; EGFR-TKI-based combinations with chemotherapy, antiangiogenic agents, EGFR-directed antibodies or other targeted agents | 9 EGFR-TKI monotherapies and 13 EGFR-TKI-based combinations (24 network nodes including chemotherapy and placebo) (n=63) |
| Comparison | Placebo; chemotherapy with or without placebo (all regimens pooled into one node); EGFR-TKI monotherapy; another eligible EGFR-TKI-based regimen | Chemotherapy (network reference), placebo and other EGFR-TKI regimens (n=63) |
| Outcomes | Primary: any-grade oral mucositis (OM, including stomatitis); secondary: grade ≥3 OM | Any-grade OM (n=61 RCTs, 20,881 participants, 24 nodes); grade ≥3 OM reported in 50 RCTs, NMA of 42 RCTs, 15,903 participants, 20 nodes after excluding 8 double-zero trials (lazertinib, aumolertinib, erlotinib + sunitinib and gefitinib + nimotuzumab absent from the grade ≥3 network) |
| Study designs | Phase II or III RCTs with ≥30 randomized participants | RCTs: 25 phase II, 37 phase III, 1 phase II/III (n=63) |
| Timing | Not specified | Not specified |
AMSTAR 2 items
Two independent extractors rated each item. Their ratings are shown side by side because they have not been reconciled yet. The overall rating follows Shea et al. 2017: one critical flaw gives Low, more than one gives Critically Low.
| Item | Extractor A | Extractor B | Agree |
|---|---|---|---|
| 1Research question includes PICO components | Yes | Yes | yes |
| 2Protocol established before the reviewcritical | Partial Yes | Partial Yes | yes |
| 3Choice of study designs explained | No | No | yes |
| 4Comprehensive literature searchcritical | Partial Yes | Yes | no |
| 5Study selection in duplicate | Yes | Yes | yes |
| 6Data extraction in duplicate | Yes | Yes | yes |
| 7List of excluded studies with reasonscritical | No | No | yes |
| 8Included studies described in detail | Partial Yes | Yes | no |
| 9Risk of bias assessed satisfactorilycritical | RCT: Yes · NRSI: N/A | NRSI: N/A · RCT: Yes | no |
| 10Funding of included studies reported | No | No | yes |
| 11Appropriate meta-analysis methodscritical | RCT: Yes · NRSI: N/A | NRSI: N/A · RCT: Yes | no |
| 12Impact of risk of bias on the pooled results | No | Yes | no |
| 13Risk of bias accounted for in interpretationcritical | Yes | Yes | yes |
| 14Heterogeneity explained | Yes | Yes | yes |
| 15Publication bias investigatedcritical | No | No | yes |
| 16Conflicts of interest reported | Yes | Yes | yes |
| Overall | Critically Low | Critically Low | yes |