(ChemotherapyAdvisor) – Sorafenib monotherapy does not improve overall survival (OS) for patients with advanced non small-cell lung cancer (NSCLC) – but an exploratory biomarker analysis suggests the oral targeted multikinase inhibitor might nevertheless prove beneficial for a subset of patients whose NSCLC tumors harbor EGFR mutations, according to reports from the randomized, double-blind, placebo-controlled Phase 3 MISSION study, presented at the European Society for Medical Oncology (ESMO) annual meeting in Vienna, Austria.

“Treatment with sorafenib does not result in improved survival as compared to placebo as a third or fourth line treatment in advanced non-small cell lung cancer,” Luis Paz-Ares, MD, of the Virgen del Rocio University Hospital in Seville, Spain, concluded.

The study enrolled 703 patients, randomizing them to receive either oral sorafenib 400 mg twice daily as a third- or fourth-line advanced NSCLC therapy, or a placebo.

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Median OS was similar between patients in the sorafenib arm and the placebo arm of the study (248 days vs 253 days; HR 0.99; P=0.4687) — despite clear superiority for sorfenib for median progression-free survival (PFS; HR 0.61; P<0.0001) and time to disease progression (HR 0.54; P<0.0001).

A separately-reported post-hoc, exploratory KRAS and EGFR mutation biomarker analysis of MISSION trial data suggested that patients whose NSCLC tumors harbor EGFR mutations, might nevertheless benefit from sorafenib, according to Tony Mok, professor of oncology at the Department of Clinical Oncology at the Chinese University in Hong Kong.

Tumor and plasma mutation data from 347 MISSION trial participants found 26% of NSCLC patients to have tumors with EGFR mutations. Patients with EGFR mutations who received sorafenib demonstrated median OS twice as long as those receiving placebo, and improved PFS, while survival did not differ between sorafenib-arm and placebo-arm patients with wild-type EGFR tumors, Dr. Mok reported.

“The better overall survival could be partly influenced by the higher number of patients receiving EGFR tyrosine kinase inhibiting drugs after the study, but the improvement in progression-free survival is mostly attributed to the use of sorafenib,” Dr. Mok reported. “This is only an exploratory analysis thus cannot confirm the value of EGFR mutation. The biomarker population is of small size, and not necessarily representative of the overall population.”

Contrary to previous findings, Dr. Mok’s team “confirmed that KRAS is not a predictive biomarker for sorafenib,” they reported.

ESMO Abstract (#LBA33_PR, LBA9_PR)