Clinical Outcomes of Afatinib Versus Osimertinib in Patients With Non-Small Cell Lung Cancer With Uncommon EGFR Mutations: A Pooled Analysis.
The purpose of this analysis was to investigate the effectiveness of afatinib compared to that of osimertinib in patients with non-small cell lung cancer (NSCLC) who harbored uncommon epidermal growth factor receptor (EGFR) mutations.
A PubMed database-based literature review was conducted to retrieve related studies. Patients harboring EGFR mutations besides the deletion in exon 19 (19del) and point mutation of L858R were included in this analysis. The primary outcome events were the objective response rate (ORR) and progression-free survival (PFS). Propensity score matching (PSM) at a ratio of 1:1 was used between afatinib and osimertinib groups to control the confounding factors. Uncommon EGFR mutations were categorized into 4 groups: insertion in exon 20 (ex20ins), non-ex20ins single uncommon EGFR mutations, compound EGFR mutations that with 19del or L858R, and compound EGFR mutations without 19del or L858R.
After PSM, 71 patients in either the afatinib or osimertinib group were matched. The afatinib group had an ORR of 60.6%, slightly higher than the osimertinib group's (50.3%), the difference was not statistically significant (P = .610). However, the afatinib group showed a significantly superior PFS benefit than the osimertinib group (11.0 vs. 7.0 months, P = .044). In addition, patients harboring non-ex20ins single uncommon EGFR mutations yield the best ORR and PFS, following treatment of either afatinib (ORR: 76.7%, mPFS: 14.1 months) or osimertinib (ORR: 68.8%, mPFS: 15.1 months). Moreover, there was no significant difference in terms of ORR or PFS between the cohort of patients treated with afatinib or osimertinib, regardless of whether or not the patients had brain metastases.
Both afatinib and osimertinib displayed favorable clinical activities toward uncommon EGFR mutations. Afatinib showed a more profound and durable PFS benefit than osimertinib, although no efficacy advantage was observed.
Wang C
，Zhao K
，Hu S
，Dong W
，Gong Y
，Xie C
... -
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Clinical outcomes of gefitinib and erlotinib in patients with NSCLC harboring uncommon EGFR mutations: A pooled analysis of 438 patients.
The purpose of this study was to investigate the outcomes of gefitinib and erlotinib in patients with non-small cell lung cancer (NSCLC) with uncommon epidermal growth factor receptor (EGFR) mutations.
Relevant researches were identified by a literature search of the PubMed database. Patients with EGFR mutations other than exon 19 deletion and L858R were eligible for the study. Clinical outcomes included objective response rate (ORR), progression free survival (PFS), and overall survival (OS). We categorized all uncommon EGFR mutations as: single uncommon EGFR mutations and compound mutations that containing 2 or more kinds of EGFR mutations. We also assessed outcomes in patients categorized by EGFR-TKIs: (1) gefitinib group; (2) erlotinib group.
A total of 438 patients with NSCLC harboring uncommon EGFR mutations were included in this study. The ORR for gefitinib and erlotinib was 43.8 %, with a median PFS (mPFS) of 6.00 months and a median OS (mOS) of 20.50 months. Patients with compound mutations had an ORR of 56.3 % and an mPFS of 8.10 months. Both of them were significantly better than these in patients with single uncommon EGFR mutation, which were 29.3 % and 3.90 months, respectively (odds ratio (ORa): 2.74, 95 % confidence interval (CI): 1.86-4.05, P < 0.001; hazard ratio (HR): 0.58, 95 % CI: 0.48-0.71, P < 0.001). Moreover, patients with compound mutations containing 19 deletion or L858R had a superior response and survival benefits compared to patients with other compound mutation patterns. In addition, the gefitinib group showed a favorable efficacy advantage (P = 0.003) and PFS benefit (P = 0.021) compared to the erlotinib group.
Uncommon EGFR mutations exhibit favorable but inconsistent treatment responses and survival outcomes to gefitinib and erlotinib, which are closely related to the mutation pattern, the cooccurring partner mutant genes, and the type of EGFR-TKIs received.
Wang C
，Zhao K
，Hu S
，Dong W
，Gong Y
，Li M
，Xie C
... -
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Efficacy and safety of osimertinib plus bevacizumab versus osimertinib alone for advanced non-small-cell lung cancer with EGFR mutations: A meta-analysis of randomized controlled trials.
To systematically evaluate the efficacy and safety of osimertinib plus bevacizumab in treating advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations.
Up to May 26, 2024, the databases of PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, China National Knowledge Infrastructure, Chinese Biomedical Literature, China Science and Technology Journal, and Wanfang were searched, and the randomized controlled clinical trials (RCTs) of osimertinib plus bevacizumab in the treatment of advanced EGFR-mutant NSCLC were included. Two researchers independently screened the literature, assessed the quality of the included literature, and extracted the literature data. Revman5.4 software was used for meta-analysis.
A total of 824 patients were included in 10 RCTs. The results of meta-analysis showed that compared with the control group (osimertinib alone), the experimental group (osimertinib plus bevacizumab) had a higher objective response rate (ORR) (relative risk [RR] = 1.23, 95% confidence interval [CI] = 1.03-1.47, P = .02), and the experimental group could significantly reduce the expression levels of carcinoembryonic antigen (mean difference [SMD] = 0.82, 95% CI = 0.30-1.35, P = .002), vascular endothelial growth factor (SMD = 0.43, 95% CI = 0.13-0.73, P = .005), neuron-specific enolase (SMD = 0.88, 95% CI = 0.60-1.17, P < .00001), cytokeratin 19 fragments (SMD = 1.33, 95% CI = 0.34-2.33, P = .009), and carbohydrate antigen 125 (SMD = 0.46, 95% CI = 0.15-0.77, P = .004) in serum. However, the experimental group did not significantly improve the disease control rate (DCR) (RR = 1.17, 95% CI = 1.00-1.36, P = .05), 1- and 2-year progression-free survival (PFS) rates (RR = 1.15, 95% CI = 1.00-1.33, P = .05; RR = 1.02, 95% CI = 0.74-1.40, P = .92), 1- and 2-year overall survival (OS) rates (RR = 1.11, 95% CI = 0.92-1.36, P = .28; RR = 0.99, 95% CI = 0.84-1.18, P = .95). Interestingly, the results of subgroup analysis showed that the experimental group significantly improved ORR, DCR, 1-year PFS, and OS rates in the Chinese population and patients under 65 years old (P < .05). In addition, when the dose of bevacizumab was 7.5 mg/kg q3w in the experimental group, ORR, DCR, 1-year PFS, and OS rates were significantly better than those in the control group (P < .05). In terms of adverse events of drugs, the incidence of proteinuria, hypertension, oral mucositis, bleeding, nausea, and vomiting in the experimental group was higher than that in the control group (P < .05).
For patients with advanced EGFR-mutant NSCLC, osimertinib plus bevacizumab has some clinical benefit compared with osimertinib alone. Still, it does not provide additional long-term survival benefits and has higher toxicity. More well-designed, multicenter RCTs are needed to identify the subgroups of patients most likely to benefit from this combination regimen and to validate the optimal dose of this combination regimen.
Yao L
，Zhang C
，Li D
，Xu L
，Yang X
... -
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ResearchGate
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