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Chemotherapy superior to TKIs in advanced, EGFR wild-type NSCLC
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Patients with advanced, EGFR wild type non–small cell lung cancer with wild-type EGFR demonstrated improved PFS when treated with conventional chemotherapy compared with EGFR tyrosine kinase inhibitors, according to results of a meta-analysis.
However, researchers observed no OS benefit.
Researchers evaluated 11 randomized controlled trials identified with the PubMed, EMBASE and Cochrane databases, and from ASCO and European Society for Medical Oncology meeting abstracts. The trials included 1,605 patients with EGFR wild-type NSCLC. Patients underwent treatment with conventional chemotherapy or an EGFR TKI such as erlotinib (Tarceva, Genentech) or gefitinib (Iressa, AstraZeneca).
Overall, patients who underwent conventional chemotherapy demonstrated significantly longer PFS compared with those who underwent therapy with an EGFR TKI (HR for TKI=1.41; 95% CI, 1.10-1.81). However, there were no statistically significant differences between the treatments for OS (HR for TKI=1.08; 95% CI, 0.96-1.22).
A higher percentage of patients assigned chemotherapy achieved an objective response (16.8% vs. 7.2%; RR for TKI=1.11; 95% CI, 1.02-1.21).
Subgroup analyses indicated treatment effects were similar with regard to line of treatment (P=.58), experimental drugs (P=.67) and dominant ethnicity (P=.78).
Trials evaluating EGFR mutation status with direct sequencing did not demonstrate improved PFS with chemotherapy vs. TKI (HR=1.12; 95% CI, 0.79-1.58); however, trials that used more sensitive platforms did demonstrate this benefit (HR=1.84; 95% CI, 1.35-2.52).
Second- or later-line chemotherapy also was associated with improved PFS vs. TKI (HR=1.34; 95% CI, 1.09-1.65).
“In the pooled analysis of all these trials, a significantly longer PFS with chemotherapy was noted in patients with wild-type EGFR tumors for the second- or later-line treatment,” the researchers wrote. “Therefore, these findings suggest that current guidelines recommending EGFR TKI as a standard treatment in this setting without consideration of the EGFR mutation status may need to be reevaluated, in consideration of the shorter PFS of TKI compared with conventional chemotherapy agents for patients with wild-type EGFR tumors.”
Disclosure: The researchers report personal fees from Bayer, GlaxoSmithKline, Novartis and Pfizer.
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