Certain BRAF Mutations in Colorectal Cancer May Respond to Anti-EGFR Therapy

Patients with metastatic colorectal cancer (CRC) who have certain BRAF mutations may be more likely to respond to anti-EGFR treatment, according to a new study published in Clinical Cancer Research.

Approximately 10% of metastatic CRC tumors harbor mutations in the BRAF gene, the study authors explained. Mutations to BRAF can cause activation and amplification of the RAS signaling pathway, which controls key functions, such as cellular proliferation and survival.

Non-V600 BRAF mutations, in particular, may be more susceptible to anti-EGFR treatment, according to results from the study. These mutations are divided into 2 separate classes: activating and RAS-independent (class 2) and RAS-dependent (class 3).

The other BRAF mutation type, known as V600, have been effectively treated with BRAF inhibitors; however, this strategy has not been successful for non-V600 mutations.

For the study, the authors retrospectively analyzed data from 40 patients with metastatic CRC whose treatment included an anti-EGFR therapy. Twelve patients had class 2 BRAF mutations and 28 patients had class 3 non-V600 mutations, according to the study.

Based on their findings, 8% of patients with tumors harboring class 2 BRAF mutations responded to anti-EGFR treatment regimens compared with 50% of those with class 3 BRAF mutations.

Additionally, 17% of patients with tumors harboring class 2 BRAF mutations responded to treatment compared with 79% of those with class 3 BRAF mutations in the first- or second-line setting. In the third-line setting or later, no patients with class 3 BRAF mutations responded to treatment compared with 37% of those with class 3 BRAF mutations, according to the study.

Overall, the study results showed that a large portion of CRCs with class 3 BRAF mutations responded to anti-EGFR therapy, whereas responses in CRCs with class 2 BRAF mutations were rare.

“Cancer genomic profiling is rapidly transforming the clinical management of cancer patients,” senior study author Hiromichi Ebi, Md, PhD, chief of the division of molecular therapeutics at the Aichi Cancer Center Research Institute, said in a press release. “Results from our study indicate that metastatic colorectal cancer patients with certain BRAF mutations should be considered for anti-EGFR treatment, a new indication for this population of patients.”

The authors did note limitations of the study, which include the small number of patients evaluated. Additionally, most patients in the study were also treated with chemotherapy and, therefore, the authors were unable to assess the efficacy of anti-EGFR monotherapy.

References

Hiromichi E, Yaeger R, Kotani D, et al. Response to anti-EGFR therapy in patients with BRAF non-V600-mutant metastatic colorectal cancer. Clinical Cancer Research. 2019. DOI: 10.1158/1078-0432.CCR-19-2004

Patients with Metastatic Colorectal Cancer Harboring Certain BRAF Mutations May Respond to Anti-EGFR Therapy [news release]. American Association for Cancer Research. https://www.aacr.org/Newsroom/Pages/News-Release-Detail.aspx?ItemID=1332. Accessed September 13, 2019.