Out of the 11 patients, five were exposed to crizotinib. and shine light around the available data for the first-line treatment of NSCLC in India keeping in mind the current standards of care in this area. first demonstrated survival benefit with doubling of overall survival (OS) with combination platinum doublet compared to the best supportive care in metastatic NSCLC.[9] Data using the second-generation combination chemotherapy, ifosfamide, mitomycin, and cisplatin, Behera exhibited response rates of 45% but with median survival of 7 months.[10] A subsequent retrospective study comparing the second-generation cisplatin-etoposide with third-generation taxane, gemcitabine combination with platinum led to 3 months improvement in survival in paclitaxel-carboplatin cohort.[11] Similar to the above, another series using the second-generation chemotherapy in the majority of patients yielded median survival of 7 months.[12] Compared to above Isocorynoxeine older series, modern series of studies with third-generation combination platinum doublet yield superior response rates in the range of 30%C50% with average improvement in median survival by 3 months, Isocorynoxeine i.e., from 7 to 10 months.[13,14,15,16,17] This improvement apart from the better selection of chemotherapeutic agents could also be because of stage migration due to the improved sensitivity of diagnosing metastatic disease using computerized tomography and positron-emission tomography compared to older generation chest X-ray and ultrasonographic techniques as part of adoption Rabbit Polyclonal to p44/42 MAPK in routine clinical practice. In landmark Phase III randomized multicentric international trial testing noninferiority of pemetrexed platinum compared to gemcitabine platinum, in which three major tertiary cancer centers of India were participants, exhibited better survival benefit of pemetrexed-based combination in adenocarcinoma and large cell histology, while gemcitabine combination favored squamous histology in preplanned subset analysis.[18] This conclusion was adopted fairly across the majority of oncology centers worldwide with Indian studies using pemetrexed-platinum combination showing progression-free survival (PFS) ranging 4C7 months and OS extending to 10 months in epidermal growth factor receptor (EGFR) unmutated cohort of patients in retrospective studies.[19,20] In Phase III randomized trial of East Asians, light/never smokers, unselected for EGFR mutation, and pemetrexed platinum followed by gefitinib maintenance was compared against upfront gefitinib use. This trial failed to show any difference in OS in any of the above groups. However, unplanned post hoc subset analysis favored upfront gefitinib in EGFR mutation NSCLC, while pemetrexed combination showed better survival in unmutated NSCLC [Table 1].[21,22,23] Table 1 First-Line Chemotherapy in Locally Advanced and Metastatic Non-small Cell Lung Cancer showed progression-free and OS of 8 and 20 months, respectively. Moreover, the patients with baseline pleural effusion had better PFS (9 vs. 7 months, = 0.02) and OS (26 vs. 18 months, = 0.05). The patients receiving more than six cycles of maintenance had improved PFS (12 vs. 7 months, = 0.002) and OS (26 vs. 16 months, = 0.05).[28] This benefit in OS with maintenance pemetrexed was similar compared to switch maintenance with tyrosine kinase inhibitors (TKIs) among patients having response to induction pemetrexed platin doublet and EGFR mutation positive.[29] Another study by Pankaj without EGFR mutation testing showed modest benefit with first-generation TKI gefitinib with PFS and OS of 5 and 7.5 months, respectively. The PFS was better in females, nonsmokers, and those who received upfront gefitinib than those who did not receive the same.[38] A study presented by Bhatt was a retrospective analysis of 106 patients. In those patients where EGFR mutation was positive, the patients were treated with either upfront TKI = 15 (14.15%) or if on chemotherapy arm finished six cycles and then given switch Isocorynoxeine maintenance TKIs, = 26 (24.52%). The median PFS for the patients with and without mutations was found to be 11 and 9 months, respectively. A median PFS of 14 months was exhibited in patients with the mutation-positive group that received both chemotherapy followed by switch maintenance with TKIs versus 8 months in the group that received only TKI.[39] Another retrospective analysis by Noronha looked into the patients who were treated with EGFR TKI. The overall response rate was 30% in the entire study population, and in the patients with EGFR-activating mutations, the response rate was 74% whereas it was only 5% in EGFR wild-type cases. The PFS was 10 months in EGFR mutation-positive cases and 2 months without EGFR mutation. The OS was 19 versus 13 months in patients with or without EGFR mutations, respectively.[40] More recent publication in a nontrial scenario, 225 patients with EGFR-activating mutation were.