Meta-analysis of Targeted Therapies in EGFR-mutated Non-Small Cell Lung Cancer: Efficacy and Safety of Osimertinib, Erlotinib, and Gefitinib as First-line Treatment.

Some of the non-small cell lung cancer (NSCLC) cases enhance somatic mutations of the epidermal growth factor receptor (EGFR) gene within the tyrosine kinase inhibitor (TKI) domain. In such cases, first-line treatments are EGFR-TKIs, including osimertinib, erlotinib, or gefitinib. Therefore, this meta-analysis aims to assess the safety and efficacy of first-line targeted therapies for EGFR-mutated advanced NSCLC patients, focusing on osimertinib, erlotinib, and gefitinib. A systematic electronic search was conducted on 3 electronic databases-Scopus, PubMed, and Web of Science-from inception to May 2024 to locate relevant trials reporting the safety and efficacy of osimertinib, erlotinib, or gefitinib in treating EGFR-mutated advanced NSCLC. No language or data restriction was applied to the search strategy. The assessed effects were objective response rate (ORR) and disease control rate (DCR). RoB 2 tool was utilized to determine the risk of bias while R programming language performed all the statistical synthesis. Out of 15,275 search results, only 19 trials were eligible for this meta-analysis. All the 3 EGFR-TKIs depicted effectiveness and safety among NSCLC patients, but osimertinib improved the ORR by 72% (95% CI: 65%, 78%) as compared with erlotinib (69% [95% CI: 58%, 79%]) and gefitinib (64% [95% CI: 64%, 78%]). Overall, the 3 EGFR-TKIs were effective by improving ORR 68% (95% CI: 63%, 73%). Similarly, osimertinib demonstrated highly effective impacts in disease control among NSCLC patients by 94% (95% CI: 91%, 97%) compared with gefitinib (68% [95% CI: 41%, 89%]). Overall, the 2 EGFR-TKIs were effective in disease control among NSCLC patients (82% [95% CI: 67%, 93%]). The pooled analyses have shown that erlotinib, gefitinib, and osimertinib are safe and effective first-line treatment options for patients with EGFR-mutated advanced NSCLC. The meta-analysis outcomes have demonstrated that osimertinib, erlotinib, or gefitinib positively impact overall response rate and disease control.

Qureshi Z ，Altaf F ，Jamil A ，Siddique R ... -  《-》

Impact of First-Line Osimertinib and Other EGFR-Tyrosine Kinase Inhibitors on Overall Survival in Untreated Advanced EGFR-Mutated Non-small Cell Lung Cancer in Japan: Updated Data from TREAD Project 01.

Hibino M ，Imamura Y ，Shimoyama R ，Fukui T ，Fukai R ，Iwase A ，Tamura Y ，Chihara Y ，Okabe T ，Uryu K ，Okuda T ，Taguri M ，Minami H ... -  《-》

Cardiac Events and Survival in Patients With EGFR-Mutant Non-Small Cell Lung Cancer Treated With Osimertinib.

Lin CY ，Chang WT ，Su PL ，Kuo CW ，Yang J ，Lin CC ，Lin SH ... -  《JAMA Network Open》

Osimertinib Efficacy and Safety in Treating Epidermal Growth Factor Receptor Mutation-Positive Advanced Non-Small-Cell Lung Cancer: A Meta-Analysis.

This study compared the safety and efficacy of osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), with those of other TKIs and its use alongside bevacizumab in patients with EGFR mutation-positive advanced non-small-cell lung cancer. PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, and VIP databases were used to conduct extensive searches for relevant randomized controlled trials until January 30, 2024. Osimertinib monotherapy favored disease control rate, whereas the comparator treatment arm favored overall survival. Using subgroup analysis, the objective response rate and progression-free survival (PFS) were significantly elevated by Osimertinib monotherapy compared with pemetrexed combined with carboplatin or cisplatin. The comparator treatment arm receiving gefitinib or erlotinib significantly favored progression-free survival and overall survival compared with osimertinib monotherapy. In patients treated with osimertinib monotherapy, the incidence of all adverse events (AEs) decreased compared with comparator treatment arm. Anemia was the only AE associated with osimertinib monotherapy. Pemetrexed combined with carboplatin or cisplatin resulted in greater loss of appetite than osimertinib monotherapy. The most associated AE of osimertinib monotherapy was diarrhea, according to network analysis. Although its efficacy is not consistent with other EGFR TKIs, osimertinib was associated with a decrease in AEs in patients with EGFR mutation-positive advanced non-small-cell lung cancer.

Zhao M ，Zhang J ，Gao J ，Wang J ，Ma Z ... -  《Clinical Pharmacology in Drug Development》

Pooled safety analysis of EGFR-TKI treatment for EGFR mutation-positive non-small cell lung cancer.

Three epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) - afatinib, erlotinib, and gefitinib - are available for the treatment of patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). Given the long-term exposure of such patients to EGFR-TKIs, the toxicological properties of these agents in these individuals may differ from those observed in unselected patients. We compared the frequencies of severe adverse events (AEs) among EGFR mutation-positive NSCLC patients treated with these three EGFR-TKIs. We performed a pooled analysis of severe AEs according to the type of EGFR-TKI administered with the use of data extracted from prospective clinical trials that evaluated the clinical efficacy of gefitinib, erlotinib, or afatinib in NSCLC patients with EGFR mutations. Twenty-one trials published between 2006 and 2014 and including 1468 patients were eligible for analysis. Patients in 13 trials (n=457) received gefitinib, those in 5 trials (n=513) received erlotinib, and those in 3 trials (n=498) received afatinib. Rash and diarrhea of grade ≥3 were significantly more frequent with afatinib therapy than with erlotinib or gefitinib therapy. The frequency of interstitial lung disease (ILD) of grade ≥3 was low (0.6-2.2%) with all three EGFR-TKIs and did not differ significantly among them. Gefitinib was associated with a significantly higher frequency of hepatotoxicity of grade ≥3 compared with erlotinib or afatinib. The overall frequency of AEs leading to treatment withdrawal was 6.1% (83 of 1354 evaluable patients), with such AEs occurring significantly more often with afatinib or gefitinib than with erlotinib. The most common withdrawal AEs were skin toxicity, ILD, and hepatotoxicity. Such information on AEs should facilitate selection of the most appropriate EGFR-TKI for EGFR mutation-positive NSCLC patients with regard to mitigation of the risk for certain types of toxicity.

Takeda M ，Okamoto I ，Nakagawa K 《-》