This article is more than 5 years old. Information may no longer be current.
Sorafenib as salvage regimen failed to extend OS in NSCLC
Click Here to Manage Email Alerts
Treatment with sorafenib as either third- or fourth-line therapy did not extend OS in patients with advanced non–small cell lung cancer, according to study results presented at the 2012 Congress of the European Society for Medical Oncology in Vienna.
However, subsequent biomarker analysis indicated an interaction between EGFR mutation status and the effect of sorafenib (Nexavar, Bayer Healthcare) on PFS.
In a prior randomized discontinuation phase 2 trial, sorafenib monotherapy exhibited significant activity among patients with advanced NSCLC who previously failed two to three chemotherapy regimens.
Based on this study, Luis G. Paz-Ares, MD, PhD, of the medical oncology department of the Hospital Universitario Virgen del Rocío in Seville, Spain, and colleagues initiated a study to resolve whether third- or fourth-line treatment with sorafenib would improve OS compared with placebo in patients with advanced relapsed/refractory NSCLC of primarily nonsquamous histology.
In the phase 3 study, 703 eligible patients were randomly assigned to oral sorafenib 400 mg twice daily or placebo. Patients also were stratified by geographic region, brain metastases, number of prior lines of treatment and prior anti-EGFR therapy.
OS was comparable between the two groups, according to study results. Median OS among patients assigned to sorafenib was 248 days compared with 253 days for those assigned to placebo (HR=0.99, P=.4687). However, median PFS (HR=0.61; P<.0001), time to disease progression (HR=0.54; P<.0001), overall response rate (P<.001) and disease control rate (P<.0001) were significantly greater in the sorafenib group.
“There are data suggesting relevant anti-tumor activity of the drug, including progression-free survival in this clinical context,” Paz-Ares said in a press release. “The fact that there is no significant impact on overall survival highlights the increasing importance of post-study therapies in lung cancer trials. In addition, one cannot exclude a potential overall survival benefit in some patient populations.”
In a post-hoc analysis using tumor and/or plasma mutation data from 347 patients who participated in the phase 3 trial, researchers detected EGFR mutations in 26% of patients and KRAS mutations in 20% of patients.
Analysis of the interaction between EGFR mutation status and the effect of treatment on survival suggested that patients with EGFR mutations benefited from sorafenib, whereas those with wild-type EGFR did not. Median OS was twice as long in patients with EGFR mutations who received sorafenib rather than placebo. Researchers found no significant difference in OS between patients with wild-type EGFR based on treatment arm.
Likewise, researchers observed an interaction between EGFR mutation status and the sorafenib effect on PFS. Patients with mutated EGFR who were treated with sorafenib exhibited better outcomes than patients with wild-type EGFR.
“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,” said Tony Mok, MD, professor in the department of clinical oncology at the Chinese University of Hong Kong.
“This is only an exploratory analysis, thus (we) cannot confirm the value of EGFR mutation,” Mok added. “The biomarker population is of small size and not necessarily representative of the overall population. But on the other hand, contrary to prior suggestions, we confirmed that KRAS is not a predictive biomarker for sorafenib.”
For more information:
Paz-Ares L. Abstract #LBA33. Presented at: 2012 European Society for Medical Oncology Congress; Sept. 28-Oct. 2, 2012; Vienna.
Disclosure: The researchers report honoraria, research funding and employment elationships with AstraZeneca, Aventis, AVEO, Bayer HealthCare Pharmaceuticals, BeiGene, BMS, Roche, Boehringer Ingelheim, Eisai, Eli Lilly, GSK Biologicals, Henrui Pharm, Merck Serono, Pfizer and Taiho.