Trials Indicate Molecular Profiling of Metastatic CRC Improves Outcomes

Clinical trials conducted during the past 5 years have shown that patients with metastatic colorectal cancer (CRC) achieve improved survival when treatment is directed to specific molecular and pathologic features of tumors, according to a recent review.

More than 1.85 million cases and 850,000 deaths worldwide are attributable to CRC. In the United States, it is the third most common cause of cancer mortality, in part because some 20% of new CRC cases present with metastatic disease.

Affecting cures of unresectable metastatic CRC is highly uncommon. Primary treatment consists of systemic therapy, including cytotoxic chemotherapy; biologic therapy, such as antibodies to cellular growth factors; immunotherapy; and combinations of these treatments.

Approximately half of patients with KRAS/NRAS/BRAF wild-type tumors who were treated in a clinical trial with cetuximab and panitumumab, in combination with chemotherapy, saw extended survival of 2 to 4 months. However, for the 35% to 40% of patients with KRAS or NRAS sequence variations, effective targeted therapies are not yet available. The trial also showed that for the 5% to 10% of patients with BRAF V600E sequence variations, targeted combination therapy with BRAF and EGFR inhibitors can extend overall survival to 9.3 months; patients with these variations who received standard chemotherapy typically survive for a median of 5.9 months.

Although cures for metastatic CRC remain uncommon, more patients can anticipate extended survival with appropriate treatment selection guided by molecular profiling.

“Advances in molecular profiling of metastatic CRC facilitate the ability to direct treatments to the biologic features of the tumor for specific patient subsets,” the authors stated. “Genomic profiling allows treatment selection so that more patients derive benefit and fewer are exposed to toxicity from ineffective therapies.”

-Angelique Platas

Reference: Biller LH, Schrag D. Diagnosis and treatment of metastatic colorectal cancer. JAMA. Published online February 16, 2021. doi:10.1001/jama.2021.0106