(ChemotherapyAdvisor) – Triple target inhibition of EGFR, VEGFR, and PDGFR with the addition of sunitinib to erlotinib did not improve overall survival (OS) compared with erlotinib alone in patients with refractory non–small-cell lung cancer (NSCLC), but the combination was associated with a significantly longer progression-free survival (PFS) and a greater objective response rate (ORR), a study in the Journal of Clinical Oncology online May 7 concluded.

The global Phase 3 randomized trial randomly assigned 960 patients previously treated with one to two chemotherapy regimens — including one platinum-based regimen — for recurrent NSCLC, and for whom erlotinib was indicated, to sunitinib 37.5mg/day or placebo plus erlotinib 150mg/day. Patients were stratified by prior bevacizumab use, smoking history, and epidermal growth factor receptor expression.

Baseline characteristics were balanced between the two arms. Prior bevacizumab use was 9.6% in the sunitinib plus erlotinib arm and 10.4% in the erlotinib alone arm.

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Median OS, the primary endpoint, was 9.0 months for sunitinib plus erlotinib vs. 8.5 months for erlotinib alone (HR, 0.922; one-sided stratified log-rank P=0.1388). Median PFS was 3.6 months vs. 2.0 months (HR, 0.807; one-sided stratified log-rank P=0.0023), and ORR was 10.6% vs. 6.9% (two-sided stratified log-rank P=0.0471), respectively.

“Never-smoking status, female sex, Asian ethnicity, ECOG PS of 0, two or fewer disease sites, and stage 3B disease were all favorable independent prognostic factors for OS by multivariate analysis,” the investigators found. “The influence of EGFR mutation or EGFR expression status could not be assessed; EGFR expression status was reported in a small number of patients (58 EGFR positive; 28 EGFR negative) because of the risks associated with collecting lung tumor tissue,” they wrote. “However, on the basis of emerging data indicating the potentially important role of molecular characterization in choosing the most appropriate targeted therapy, we strongly recommend that tumor tissue be collected for molecular analysis in future trials. Ideally, molecular profiling should occur before initiating treatment to allow a specific therapy with promising efficacy, if available, to be selected.”

Treatment-related toxicities grade ≥3 were more frequent in the sunitinib plus erlotinib arm and included rash/dermatitis, diarrhea, and asthenia/fatigue.