Panitumumab improves survival in wild-type KRAS or RAS colorectal cancer

Last Updated: 2016-10-25

By Will Boggs MD

NEW YORK (Reuters Health) - The anti-EGFR monoclonal antibody panitumumab improves overall survival in patients with chemorefractory wild-type KRAS or RAS metastatic colorectal cancer, according to results from a phase 3 trial.

Panitumumab has been shown to be effective as monotherapy and in combination with chemotherapy for treating patients with metastatic colorectal cancer. Outcomes are better in patients with wild-type KRAS, but whether RAS status reliably predicts outcomes has not been clear.

Dr. Tae Won Kim from the University of Ulsan in Seoul, South Korea, and colleagues randomized 377 patients with wild-type KRAS exon 2 mCRC to receive panitumumab (6 mg/kg Q2W) plus best supportive care (BSC) or BSC alone.

Among the patients with wild-type KRAS, median overall survival was 10.0 months in the panitumumab group versus 7.4 months in those receiving only BSC (p<0.01), the team reports in the British Journal of Cancer, online October 13.

Progression-free survival (PFS) and objective response rates (ORR) were also significantly better in the panitumumab group.

Panitumumab treatment also improved overall survival among patients with wild-type RAS tumors (10.0 vs. 6.9 months, p=0.01). In this group, PFS and ORR were numerically better with panitumumab treatment.

In contrast, patients with wild-type KRAS tumors but with RAS mutations did not benefit from panitumumab therapy.

Adverse events of any grade were much more common with panitumumab plus BSC than with BSC alone. The incidences of grade 3/4 hypomagnesemia, skin rash and dermatitis acneiform were all 6%, in the panitumumab group, compared to 1%, 1% and 0%, respectively, for BSC alone.

"The results from the prospective 20100007 trial indicate panitumumab therapy significantly improved OS and PFS, and numerically improved ORR in patients with chemotherapy-refractory wild-type KRAS exon 2 and wild-type RAS metastatic colorectal cancer vs BSC alone," the researchers conclude.

"RAS analysis from the 20100007 study definitively confirms the negative predictive value of activating RAS mutations for response in patients with metastatic colorectal cancer receiving panitumumab monotherapy," they add.

Dr. Kohei Shitara from National Cancer Center (NCC) Hospital East in Kashiwa, Japan, who has also found different panitumumab outcomes among colorectal cancer patients with and without RAS mutations, told Reuters Health by email, "Panitumumab is effective for all RAS wild-type patients. Already NCC guideline (and the) Japanese label indicate panitumumab should be used for all RAS wild-type patients."

Dr. Marwan Fakih from City of Hope Comprehensive Cancer Center in Duarte, California, said, "The current study confirms our prior expectations that panitumumab should be superior to best supportive care in overall survival."

"The message from this study is clear," he told Reuters Health by email. "Panitumumab is a valid option as a salvage treatment in patients with RAS wild-type colon cancer who progressed on prior standard cytotoxic therapy. Panitumumab monotherapy is associated with a high response rate and results in a clinically significant improvement in PFS and overall survival, with an acceptable toxicity profile."

Neither physician was involved in the study.

Amgen Inc. sponsored the trial and had various relationships with several of the reports' authors, including employment.

Dr. Kim did not respond to a request for comments.

SOURCE: http://bit.ly/2eC1qgR

Br J Cancer 2016.