November 2012, Vol 1, No 5

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EGFR Mutations, Not KRAS Mutations, May Be Predictive for Sorafenib Response in Advanced NSCLC

Phoebe Starr

Uncategorized

Treatment with sorafenib did not improve overall survival (OS) in patients with heavily pretreated advanced non–small cell lung cancer (NSCLC) in the overall analysis of the MISSION trial reported at the 2012 ESMO Congress. A post hoc companion biomarker study of MISSION presented at the same meeting suggested that EGFR mutated status may be predictive of a benefit with sorafenib treatment; however, KRAS mutations were not predictive of response.

“The biomarker analysis hinted that mutated EGFR may be predictive for sorafenib, but interpret these data with caution,” stated lead author Tony S. Mok, MD, Chinese University of Hong Kong. He pointed out that this analysis was based on a small sample size and was exploratory.

The global multicenter, randomized, phase 3 MISSION trial compared sorafenib plus best supportive care with best supportive care alone as third- or fourth-line therapy in 703 patients with advanced NSCLC. Patients were not preselected or prestratified according to EGFR or KRAS status.

After the trial was completed, mutational analysis was performed on 347 patients. EGFR mutations were detected in 26% and KRAS mutations in 20%. Mutational status was balanced between the 2 treatment arms.

Mutated EGFR was identified in tumor tissue or plasma in 44 patients treated with sorafenib and 45 receiving placebo. Wild-type EGFR was found in 122 of sorafenib-treated patients and in 136 in the group receiving placebo.

Sorafenib demonstrated a significant progression-free survival (PFS) benefit in patients with mutated EGFR: median PFS was 2.7 months with sorafenib versus 1.4 months with placebo (P<.001). PFS was also significantly better with sorafenib in the wild-type EGFR patients: median of 2.7 months versus 1.5 months, respectively (P<.001).

Sorafenib-treated patients with EGFR mutations had significantly superior OS compared with placebo; OS was 13.9 months on sorafenib versus 6.5 months for those receiving placebo (P=.002). However, no OS difference was found between groups in patients with wild-type EGFR; median OS was 8.3 months with sorafenib and 8.4 months with placebo. The biomarker treatment interaction analysis had a P value of .015 for PFS and .023 for OS.

The interaction analysis suggests that EGFR status is a potential biomarker for sorafenib response, Mok noted.

No significant PFS or OS benefit was observed for sorafenib in either KRAS mutated or KRAS wild-type NSCLC. For KRAS mutation, the biomarker treatment interaction analysis had a P value of .696; for KRAS wild-type, the biomarker interaction analysis had a P value of .743.

KRAS mutation status did not appear to influence response to sorafenib. The interaction analysis was negative for both PFS and OS,” Mok said.

“Based on current data, we hypothesize that EGFR mutation is a predictive biomarker for sorafenib in treatment of patients with advanced NSCLC,” Mok stated. He added that the search for biomarkers that predict response is critical for progress. “Otherwise we are treating blindly in the dark,” he commented.

Interview with the Innovators - November 19, 2012

Cultivating Personalized Medicine Clinical Acumen in the Management of Breast Cancer:

An Interview with Edith Perez, MD

If any cancer can be said to have launched personalized medicine into orbit and establish it as the standard for all cancer therapy to aspire toward, it is breast cancer. The discovery of the estrogen receptor (ER) and HER2 biomarkers has astonished healthcare professionals and the public alike and raised [ Read More ]

Uncategorized - November 19, 2012

Whole Genome Testing Moves Forward in Breast Cancer

Researchers presented the first large study to test the entire genome of individualized breast cancers to help personalize cancer at the 2012 ESMO Congress. They found that this approach is feasible and enables identification of genetic alterations that can be targeted by available drugs. They also saw early signs of [ Read More ]