Pemetrexed Versus Pemetrexed and Carboplatin As Second-Line Chemotherapy in Advanced Non–Small-Cell Lung Cancer: Results of the GOIRC 02-2006 Randomized Phase II Study and Pooled Analysis With the NVALT7 Trial

Abstract

Second-line treatment of advanced NSCLC with pemetrexed plus carboplatin does not improve survival outcomes as compared with single-agent pemetrexed. The benefit observed with carboplatin addition in squamous tumors may warrant further investigation.

Efficacy of First-line Chemotherapy Affects the Second-Line Setting Response in Patients with Advanced Non-Small Cell Lung Cancer

“…The association between the efficacy of first-line treatment or related baseline factors and ORR for secondline treatment was assessed using the Chi-square test (Ardizzoni et al, 2012). The Kaplan-Meier method was used to estimate PFS and OS and the log-rank test was used to compare survival curves (Di Maio et al, 2012).…”

“…However, only a minority of patients express these markers, with EGFR mutations detected in about 30-40% and EML4-ALK fusions in about 4% in an East Asian population (Zhou et al, 2011;. So for the majority of patients without driver mutations, platinum-based chemotherapy remains the standard first-line treatment (Natukula et al, In this subpopulation, patients are recommended to receive second-line chemotherapy such as doctacel or pemetrexed when first-line treatment fails (Hanna et al, 2004;Caponi et al, 2010;Ardizzoni et al, 2012) However, the efficacy of second-line chemotherapy is still dismal, with a response rate of about 10%, PFS of 2-3 months and OS of 6-9 months (Hanna et al, 2004;de Marinis et al, 2011;Ardizzoni et al, 2012). More importantly, currently, there are also still no identified predictive factors to predict the efficacy of second-line chemotherapy (Favaretto et al, 2009;de Marinis et al, 2011).…”

Non-small cell lung cancer recurrence following surgery and perioperative chemotherapy: Comparison of two chemotherapy regimens (IFCT-0702: A randomized phase 3 final results study)

“…It should be emphasized that no detrimental effect on the patient-reported assessments was observed in the doublet arm. While platinum-doublets have been the backbone of first-line regimens for over 10 years [24], they have failed to improve OS in the second-line setting, despite improving PFS and response rate [14,15]. In a 2009 meta-analysis [25], doublet chemotherapy was compared to single-agent therapy as second-line treatment of advanced NSCLC, with significantly improved response rate and PFS, yet not OS, and all at the cost of increased toxicity.…”

“…Randomized studies comparing platinum-based doublets vs. single-agent chemotherapy in second-line chemotherapy for Stage IV NSCLC have reported improved response rates and progression free survival (PFS), yet not overall survival (OS) [14,15]. So far there have been no trials addressing the role of platinum agents for patients pretreated with chemotherapy-surgery.…”

Predictive role of erythrocyte macrocytosis during treatment with pemetrexed in advanced non-small cell lung cancer patients

“…Indeed, nonsquamous histology represents the principal predictor of efficacy in NSCLC patients treated with pemetrexed. This evidence emerged from retrospective analyses and is probably related to low expression of thymidylate synthase (TS) enzyme, the principal target of pemetrexed activity [7][8][9][10][11]. However, TS expression does not seem to allow patient selection for pemetrexed therapy and, to date, validated predictive factors of pemetrexed efficacy in patients with non-squamous histology are still missing.…”