RAS status determined panitumumab benefit in colorectal cancer

Issue: February 25, 2014

Additional RAS testing beyond exon 2 may be necessary to identify patients with metastatic colorectal cancer who are unlikely to benefit from treatment with panitumumab, according to phase 3 study results presented at the 2014 Gastrointestinal Cancers Symposium.

Perspective from Smitha Krishnamurthi, MD

“By testing for RAS mutations, doctors will be able to better select among metastatic colorectal cancer patients and only recommend panitumumab treatment to those who are most likely to benefit,” Marc Peeters, MD, PhD, professor of oncology at Antwerp University Hospital in Edegem, Belgium, said in a press release. “These results confirm that it is RAS status that matters, not just KRAS, when determining if panitumumab therapy could be beneficial. For patients with a RAS mutation, these findings will spare them the costs and side effects of a treatment that will not improve their outcomes.”

Peeters and colleagues analyzed data from a study that evaluated panitumumab (Vectibix, Amgen) plus FOLFIRI vs. FOLFIRI alone in 1,186 patients.

Initial results showed the addition of panitumumab to FOLFIRI significantly improved PFS (HR=0.73; 95% CI, 0.59-0.9), with a trend toward improved OS (HR=0.85; 95% CI, 0.7-1.04). RAS mutation data were available in 85% of the study population.

In the current analysis, researchers conducted further sequencing on KRAS exons 3 and 4 and NRAS exons 2, 3 and 4.

Among 597 patients with wild-type KRAS exon 2, 18% harbored additional RAS mutations beyond exon 2.

Researchers found the improved median OS with panitumumab plus FOLFIRI was more prominent among patients with wild-type RAS compared with mutated RAS (16.2 months vs. 11.8 months).

Median PFS also was improved among patients with wild-type RAS vs. mutated RAS (6.4 months vs. 4.8 months).

Among patients with mutated RAS, researchers observed no significant differences between those treated with panitumumab plus FOLFIRI vs. FOLFIRI alone in terms of median OS (11.8 months vs. 11.1 months) and median PFS (4.8 months vs. 4 months).

“Patients with mutated tumors in the RAS genes are unlikely to benefit with the addition of panitumumab to FOLFIRI, similar to what was seen in the patients with only the KRAS exon 2 mutation,” Peeters said during a press conference. “These results clearly support the fact that we need RAS testing when we want to treat our patients with panitumumab in the setting of colorectal cancer.”

For more information:

Peeters M. Abstract #LBA387. Presented at: 2014 Gastrointestinal Cancers Symposium; Jan. 16-18, 2014; San Francisco.

Disclosure: The researchers report various financial relationships with Amgen, Bayer, Biocompatibles, Celgene, Fresenius Biotech, Ganymed Pharmaceuticals, GlaxoSmithKline, Merck, Pfizer, Roche and Sanofi.

Perspective

Smitha Krishnamurthi, MD

We’ve seen that the expanded RAS testing identified an additional 18% of patients who did not benefit from panitumumab in the second-line setting. This is very close to the additional 17% of patients identified as RAS-mutant with expanded testing in the PRIME study of FOLFOX and panitumumab as first-line therapy that was recently published. These results, as well as data from the PRIME and FIRE trials and other studies that will be presented at this symposium, indicate that expanded RAS testing should become the standard of care to best identify patients who will benefit from anti-EGFR therapy.

Smitha Krishnamurthi, MD

Associate professor of medicine

University Hospitals Case Medical Center

Case Western Reserve University

Disclosures: Krishnamurthi reports honoraria and research funding from Nektar and UpToDate.