Addition of sorafenib to chemotherapy does not prolong survival

Sep 13 2012

By medwireNews Reporters

The addition of sorafenib to gemcitabine/cisplatin fails to provide any additional benefit in chemotherapy-naïve patients with nonsquamous non-small-cell lung cancer (NSCLC), research shows.

In the phase III study of 772 patients with stage IIIb or IV nonsquamous NSCLC, the median overall survival (OS) was 12.4 months in the sorafenib plus gemcitabine/cisplatin group and 12.5 months in the placebo plus gemcitabine/cisplatin group.

Sorafenib is an oral transduction inhibitor that works by targeting kinases involved in tumor cell proliferation and angiogenesis.

"This trial did not meet its primary objective of improving OS when sorafenib was added to gemcitabine/cisplatin for the first-line treatment of patients with advanced, nonsquamous NSCLC," report Luis Paz-Ares (Hospital Universitario Virgen del Rocío, Seville, Spain) and colleagues in the Journal of Clinical Oncology.

Investigators did observe a trend toward progression-free survival (PFS) and a significant improvement in the time-to-progression (TTP) of cancer.

For the NSCLC Research Experience Utilizing Sorafenib (NEXUS) trial, 385 patients were randomly allocated to receive treatment with sorafenib 400 mg twice daily and 387 patients were randomly allocated to receive placebo.

All patients were treated with gemcitabine 1250 mg/m² per day on days 1 and 8 and cisplatin 75 mg/m² on day 1. During the chemotherapy phase, patients received up to six cycles consisting of 21 days.

The median duration of treatment in the sorafenib plus gemcitabine/cisplatin group was 17 weeks and 18 weeks in the placebo plus gemcitabine/cisplatin group.

There was no significant improvement in OS among patients who received sorafenib.

The median PFS was 6.0 months in the sorafenib plus gemcitabine/cisplatin group and 5.5 months in the placebo arm, but this difference did not reach statistical significance .

The median TTP was 6.1 months in the sorafenib-treated patients and 5.5 months among those receiving placebo and gemcitabine/cisplatin, a 27% difference that was statistically significant.

A secondary analysis of tumor progression did not show a difference between the two treatment arms.

The researchers note that many randomized phase III clinical trials have failed to show that the addition of molecularly targeted agents to chemotherapy improves survival in patients with advanced NSCLC. In contrast, erlotinib and gefitinib have been shown to be effective as monotherapy in these patients.

"Studies using novel biomarker-based approaches may guide the selection of individualized targeted therapies," write Paz-Ares and colleagues.

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