Conventional Chemo Bests Tyrosine Kinase Inhibitors in Wild-Type Lung Cancers

Frontline Medical News, 2014 Apr 08, MA Moon

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David Muñoz Carmona

Conventional chemotherapy prolonged progression-free survival and induced a higher tumor response rate, compared with tyrosine kinase inhibitors, in a meta-analysis involving 1,605 patients with advanced wild-type non–small cell lung cancer, according to a report published online April 8 in JAMA.

First-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors such as erlotinib and gefitinib are first-line treatments for non–small cell lung cancers that are known to harbor EGFR-activating mutations, but their benefit is less pronounced against wild-type NSCLCs (no mutation detected in the EGFR gene). Several small studies assessing the efficacy of these agents in wild-type NSCLCs have produced inconclusive results, mostly because of the small number of participating patients, said Dr. June-Koo Lee of the department of internal medicine, Seoul (Republic of Korea) National University Hospital, and associates.

The investigators therefore pooled data from a meta-analysis of 11 randomized, controlled, open-label trials, to obtain sufficient data to compare EGFR tyrosine kinase inhibitors (811 patients) against conventional chemotherapeutic agents such as cisplatin, carboplatin, docetaxel, and pemetrexed (794 patients) in wild-type NSCLCs.

Progression-free survival was significantly longer with conventional chemotherapy than with EGFR tyrosine kinase inhibitors (6.4 vs 1.9 months; hazard ratio, 1.41; 95% confidence interval, 1.10-1.81). Conventional chemotherapy also induced a significantly higher objective response rate than did tyrosine kinase inhibitors (16.8% vs 7.2%; relative risk of nonresponse from tyrosine kinase inhibitors, 1.11; 95% CI, 1.02-1.21).

Overall survival was not significantly different between the two study groups, but that “can be explained by the large crossover rates of the included trials,” Dr. Lee and associates reported (JAMA 2014;311:1430-7).

The findings “suggest that current guidelines recommending EGFR tyrosine kinase inhibitors as a standard treatment in this setting ... may need to be reevaluated,” they wrote.

However, it is important to note that a treatment’s toxicity profile is crucial when choosing among different options, and EGFR tyrosine kinase inhibitors are known to have a better toxicity profile than standard chemotherapeutic agents. They should therefore be considered for certain patients, such as those who have a poor performance status, the investigators said.

This study was supported in part by the National Research Foundation of Korea. Dr. Lee reported no financial conflicts of interest; two coauthors reported ties to Pfizer, Lilly, and other companies.