Dr. Marwan Fakih

An expert explains the importance of genetic testing in metastatic colorectal cancer, as recent FDA approval highlights its role in guiding targeted treatments.

The Importance of Genetic Testing in Metastatic Colorectal Cancer

Genetic testing is a laboratory method used to detect changes in genes, gene expression or chromosomes in a person's cells or tissues, according to the National Cancer Institute. Genetic testing may identify inherited gene changes that indicate an increased risk of developing a disease or condition or passing it to a family member, which is called germline testing. Genetic testing can also analyze tumor tissue for genetic changes in cancer cells that develop during a person’s lifetime and are not inherited, which is known as somatic testing and helps assess the cancer, guide treatment or monitor treatment response.

Recent advances in precision medicine have resulted in new treatments targeting genetic mutations. Notably, findings from the phase 3 CodeBreaK 300 trial have supported the use of a combination of Lumakras (sotorasib) and Vectibix (panitumumab) for patients with KRAS G12C-mutated metastatic colorectal cancer, as reported by Amgen, the manufacturer of the drugs.

On Jan. 16, the FDA approved a combination therapy for adults who previously received chemotherapy based on fluoropyrimidine, oxaliplatin and irinotecan, according to Amgen. This approval was based on findings from the CodeBreaK 300 trial.

CURE spoke with Dr. Marwan G. Fakih, lead investigator and professor of medical oncology at City of Hope in Duarte, California, about the importance of genetic testing, especially in a metastatic colorectal cancer setting.

So, in this day and age, every single patient with metastatic colorectal cancer should have upfront what we call next-generation sequencing of their treatment, meaning full profiling of the genetic alterations of their cancer. I think it's not acceptable not to know if a patient has a KRAS mutation, and it's not acceptable not to know what is that mutation. So that's part of the standard of care that has been the recommendation of the American Society of Clinical Oncology, to do KRAS testing, and the NCCN guidelines, that is standard guidelines across the world. I think what we have to learn as providers is to pay attention as to what is the mutation, because the main reason we used to test for KRAS is to know if a patient is candidate or not for Vectibix, which is panitumumab or Erbitux, which is cetuximab, those are targeted therapies, and in the presence of a KRAS mutation, those drugs should not be used.

Transcript has been edited for clarity and conciseness.

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Dr. Marwan G. Fakih explains that KRAS mutations, found in 45% of patients with colorectal cancer, include the rare KRAS G12C mutation, leading to Lumakras approval.

Explaining KRAS Mutations For Patients With Colorectal Cancer

According to the National Cancer Institute's website, KRAS is a gene that makes a protein involved in cell signaling pathways that regulate cell growth, maturation and death. The normal form of the gene is called wild-type KRAS, while mutated forms have been found in cancers such as non-small cell lung, colorectal and pancreatic cancer. These mutations can cause cancer cells to grow and spread throughout the body. Identifying whether a tumor has a wild-type or mutated KRAS gene is important for planning treatment strategies.

Advancements in precision medicine have led to new treatments aimed at KRAS mutations, including recent findings from the phase 3 CodeBreaK 300 trial. This trial supported the combination of Lumakras (sotorasib) and Vectibix (panitumumab) for patients with KRAS G12C-mutated metastatic colorectal cancer, according to Amgen, the drug’s manufacturer.

On Jan. 16, the FDA approved this combination therapy for adults who previously received fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, according to Amgen. This approval was based on the phase 3 CodeBreaK 300 trial.

CURE spoke with Dr. Marwan G. Fakih, lead investigator and professor of medical oncology at City of Hope in Duarte, California, about the KRAS G12C mutation in colorectal cancer and the development of targeted therapies like Lumakras, the first KRAS inhibitor approved in the United States.

KRAS mutations are present in about 45% of patients [with colorectal cancer], and KRAS G12C is not the most common one. The KRAS G12C-[mutation] happens to be one of the rare KRAS mutations, occurring in 4% of patients. But this particular mutation is more druggable, [and] more amenable to inhibition. And it was one of those mutations where there has been early progress in identifying molecules that can bind to it and completely block it. And [Lumakras] was really the first of such agents to move into the clinic and show effectively responses in patients with KRAS G12C mutation. And this lies not just for colon cancer, but other tumor types, such as lung cancer, where it is also approved, but that is the significance of the KRAS G12C [mutation]. It's really has a configuration that allowed earlier-on development of drugs that can target it. And the field has moved forward since, and there are other agents now being evaluated in other KRAS mutations. And [Lumakras] is really the first to be approved as a KRAS inhibitor in the United States.

Dr. Marwan Fakih

The Importance of Genetic Testing in Metastatic Colorectal Cancer

Explaining KRAS Mutations For Patients With Colorectal Cancer

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