Meta-analysis of various TKI generations efficacy either alone or in combinations in EGFR mutated NSCLC

Background. Multiple options of first line treatment in patients with EGFR mutated NSCLC are registered worldwide and, in particular, in Russia. The individual choice for every patient is still based primarily on personal preference of a particular physician and financial possibilities of the region, since no stratification factors are available. At the same time large randomized trials comparing various options are hardly possible in this narrow biomarker restricted population. The additional information on advantages in particular subgroups obtained via indirect comparison might be an important argument. Materials and methods. We conducted meta-analysis of trials studying various approaches in first line EGFR mutated NSCLC cancer. Results. Our meta-analysis revealed unequal influence of different treatment approaches on OS according to clinical stratification factors. In females (HR 0.79, 95 % CI 0.63-0.99; p = 0.04), patients younger than 65 y. o. (HR 0.66, 95 % CI 0.52-0.83; p = 0.0004), with exon 21 mutations (HR 0.76, 95 % CI 0.59-0.99; p = 0.04) and ECOG 1 (HR 0.72, 95 % CI 0.59-0.89; p = 0.002) OS benefit can be achieved with 2nd generation TKI. In the rest of patients (males, ECOG 0, ex19 deletions) increase in OS necessitates more aggressive treatment with TKI and chemotherapy combination (HR 0.57, 95 % CI 0.41-0.79; p = 0.0008). No influence on OS was observed for TKI and angiogenesis inhibitors. Interestingly, the observed advantage in OS and PFS was not accompanied by response that did not differ between regimens (OR 1.55, 95 % CI 0.86-2.80; p = 0.14). Conclusions. We showed the importance of individualized approach in the first line EGFR mutated NSCLC selection. Our results underline the need for the new data on various approaches comparison.