SYSTEMATIC REVIEW AND META-ANALYSIS OF THE EFFICACY AND SAFETY OF TARGETED AND IMMUNOTARGETED AGENTS IN THE TREATMENT OF NON-SMALL CELL LUNG CANCER

196 Volume 5, Issue 10: Special Issue (EJAR) ISSN: 2181-2020 MPHAPP THE 6TH INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE “MODERN PHARMACEUTICS: ACTUAL PROBLEMS AND PROSPECTS” TASHKENT, OCTOBER 17, 2025 in-academy.uz SYSTEMATIC REVIEW AND META-ANALYSIS OF THE EFFICACY AND SAFETY OF TARGETED AND IMMUNOTARGETED AGENTS IN THE TREATMENT OF NON-SMALL CELL LUNG CANCER Rajabova N.Kh. Tashkent Pharmaceutical Institute, Tashkent city, Republic of Uzbekistan e-mail: [email protected] https://doi.org/10.5281/zenodo.17332714 Relevance: non-small cell lung cancer (NSCLC) remains one of the leading causes of cancerrelated morbidity and mortality worldwide. The introduction of targeted therapies (EGFR, ALK, ROS1 inhibitors, etc.) and immune checkpoint inhibitors (PD-1/PD-L1) has markedly transformed therapeutic strategies, shifting clinical practice toward a more personalized approach. Despite notable advances, a systematic evaluation of accumulated data is required to determine the optimal sequencing and combination of treatments, as well as to balance clinical efficacy with safety outcomes. Purpose of the study: to conduct a systematic review and meta-analysis of clinical trials comparing the efficacy and tolerability of targeted therapies and immunotherapeutic agents in NSCLC. Materials and methods: a literature search was performed in PubMed, Embase, and the Cochrane Library for the period 2015–2024. Eligible studies included randomized clinical trials and meta-analyses reporting overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse event profiles. Pooled estimates were calculated using a random-effects model, and interstudy heterogeneity was assessed with the I² statistic. Results: а total of 36 studies, including over 14,000 patients, were analyzed. In patients with driver mutations, targeted therapies significantly improved PFS (HR = 0.48; 95% CI: 0.41–0.56) and increased ORR up to 65%, markedly outperforming chemotherapy. Immunotherapy with PD-1/PDL1 inhibitors demonstrated a clinically meaningful OS benefit in patients without EGFR/ALK mutations and with high PD-L1 expression (≥50%) (HR = 0.74; 95% CI: 0.66–0.83). Safety analysis revealed distinct toxicity profiles: targeted therapies were associated with dermatologic and gastrointestinal adverse events, whereas immunotherapy was more frequently linked to immunerelated toxicities such as pneumonitis, thyroid dysfunction, and colitis. Conclusions: This meta-analysis supports the preferential use of targeted therapies in patients with defined molecular alterations and highlights the efficacy of immunotherapy in cohorts with high PD-L1 expression and no driver mutations. Optimal therapeutic strategies should be guided by molecular profiling and biomarker assessment. Combination regimens involving targeted and immunotherapeutic agents represent a promising direction, warranting further multicenter trials and pharmacoeconomic evaluation within national healthcare systems.