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Sorafenib benefited patients with RAS, BRAF mutations
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Patients with radioactive iodine-refractory differentiated thyroid cancer demonstrated longer PFS after treatment with sorafenib than placebo regardless of BRAF or RAS mutation status, according to study results presented at the European Cancer Congress.
Researchers involved with the phase 3 DECISION trial reported that treatment of radioactive iodine (RAI)-refractory differentiated thyroid cancer with sorafenib (Nexavar, Bayer) reduced the risk of progression or death by 42% compared with placebo.
However, several genetic abnormalities have been implicated in the etiology of differentiated thyroid cancers.
Marcia S. Brose
Marcia S. Brose, MD, PhD, director of the thyroid cancer therapeutics program and assistant professor of otorhinolaryngology at the Abramson Cancer Center and Perelman School of Medicine at the University of Pennsylvania, and colleagues examined the effectiveness of sorafenib on thyroid cancers that harbor BRAF and RAS mutations.
Patients with locally advanced/metastatic RAI-refractory differentiated thyroid cancer that progressed in the previous 14 months were randomly assigned 1:1 to sorafenib 400 mg orally twice daily or placebo. Patients assigned to placebo were permitted to receive sorafenib upon cancer progression.
Tumor mutation data was available from 256 patients (61.4% of the study population), including 126 in the sorafenib arm and 130 in the placebo arm. Demographics of the genetic subgroup were similar to the overall study population.
BRAF mutations were detected in 30.1% of patients and RAS mutations were found in 19.5% of patients. Mutation status was well balanced in both arms. Other point mutations were identified in less than 5% of patients, and 47.3% of patients had no detectable mutations.
Among patients assigned to placebo, those with mutant RAS tumors demonstrated worse PFS outcomes than those with wild-type RAS tumors (HR=1.78, P=.03). Those with mutant BRAF tumors demonstrated better PFS outcomes than those with wild-type BRAF tumors (HR=0.53, P=.01). Researchers observed no significant difference in OS with either mutation.
Patients with both wild-type and mutant BRAF tumors demonstrated improved PFS when treated with sorafenib compared with placebo (wild-type BRAF: HR=0.54, P<.001; mutant BRAF: HR=0.47, P=.02; interaction P value=.68).
Sorafenib-treated patients benefited independently of RAS mutation status in terms of PFS prolongation (wild-type RAS: HR=0.6, P=.004; mutant RAS: HR=0.45, P=.037; interaction P value=.39).
The number of events were small, but mutant BRAF patients treated with sorafenib appeared to exhibit improved OS compared with placebo (HR=0.32, P=.03). Researchers reported no difference in OS based on RAS mutation status.
“Our results are important because they show that, regardless of the presence of these two common genetic changes, the group that was treated with sorafenib did better than the placebo,” Brose said in a press release. “There was no subgroup that didn't appear to benefit from the intervention with the sorafenib.”
For more information:
Brose MS. Abstract #3155. Presented at: The European Cancer Congress 2013; Sept. 27-Oct. 2, 2013; Amsterdam.
Disclosure: The researchers reported advisory board positions, corporate-sponsored research and employment relationships with AstraZeneca, Bayer HealthCare Pharmaceuticals, Eisai, Exelixis, Genzyme and Onyx Pharmaceuticals.