Post-hoc analysis of the PETACC-8 trial tied KRAS and BRAF V600E mutations to shorter overall and disease-free survival in patients with microsatellite stable (MSS) colon cancer.1

“First, these mutations do not bear the same prognostic value in microsatellite instability (MSI; which occurs in approximately 10% of patients with stage 3 colon cancer) and MSS tumors (90%). When looking at BRAF mutation V600E, it is clear in this work that it has an impact not only on survival after relapse (metastatic disease) but also on disease recurrence itself. As overall survival is constituted of time to relapse and survival after relapse, BRAF mutation also negatively impacts overall survival. Concerning KRAS mutations, they are also prognostic for all 3 outcome parameters (disease-free survival, overall survival, survival after recurrence) in the MSS patients,” Julien Taieb MD, PhD, of the Department of Gastroenterology and Digestive Oncology at the European Georges Pompidou Hospital in Paris France, wrote in an email to Cancer Therapy Advisor.

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Stage at diagnosis of colorectal cancer (CRC) is an important prognostic factor. However, tumor characteristics can have prognostic value that is independent of the tumor stage.

For instance, the BRAF V600E mutation has been linked to a poor prognosis whereas resistance to epidermal growth factor receptor inhibitors in metastatic CRC is associated with KRAS mutations.

The authors of the study, published in JAMA Oncology, said that the prognostic impact of KRAS and BRAF mutations in nonmetastatic CRC is not fully understood.

Taieb and colleagues conducted the post-hoc analysis of the PETACC-8 randomized clinical trial to assess the prognostic impact of KRAS and BRAF mutations in a cohort of patients receiving adjuvant FOLFOX (fluorouracil, leucovorin, oxaliplatin) with or without cetuximab for stage 3 colon cancer.

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In the original study, patients were randomized to receive 6 months of chemotherapy after tumor resection. Overall survival and disease-free survival were assessed based on the patients’ BRAF and KRAS statuses.

Of the 1791 participants in the phase 3 PETACC-8 trial with tumor specimens, 9.9% (n = 177), 9.0% (n = 148), and 33.1% (n = 588) demonstrated evidence of MSI phenotype, BRAF V600E, and KRAS mutations, respectively.