Amidst an arguably stagnant therapeutic landscape in colorectal cancer, a rare breakthrough was made for colorectal cancer patients harboring a KRAS mutation, available at Virginia Cancer Specialists.
According to the SEER cancer database, colorectal cancer is currently the fourth most common type of cancer in the United States, with 151,030 estimated cases in 2022, amounting to a lifetime approximated risk of 4.1%. Colorectal cancer is also unfortunately an aggressive and deadly cancer, causing 52,580 deaths in 2022,
Although early-stage colorectal cancers generally have good prognosis and are often curable through surgery and chemotherapy, metastatic cancers present a therapeutic challenge. For more than two decades, the cornerstone of treatment has been fluoropyrimidine-based chemotherapy, and patients are left with limited options upon disease progression.
KRAS is the most frequently mutated gene in human cancers and mutations in this gene can be found in up to 50% of colorectal cancers. Historically, these mutations have conferred poor prognoses and resistance to many existing treatment options such as standard EGFR targeting agents. For many years, it was felt that KRAS mutations were “undruggable” due to many failed attempts to target this mutation in drug development.
A promising breakthrough in targeting KRAS mutated colorectal cancers was published in the New England Journal of Medicine on January 5, 2021 and was met with great excitement. Dr. Alex Spira from Virginia Cancer Specialists is one of the leading investigators in this study*. In this phase 1/2 trial in which Virginia Cancer Specialists participated, Adagrasib, a specifically designed small molecule drug directed towards KRAS, demonstrated significant clinical benefit in patients who had already been heavily pretreated with chemotherapy.
With 44 total patients enrolled, the study demonstrated a median duration of response of 7.6 months (95% CI, 5.7 to not estimable) and progression-free survival of 6.9 months (95% CI 5.4 to 8.1) among patients who received Adagrasib combined with Ctuximab (an existing therapy). In contrast, the historical progression-free survival in similarly pretreated patients was only around 2 months with available FDA-approved therapies. While larger phase 3 research will seek to confirm these results, this early phase study has provided a beacon of hope for colorectal cancer patients with this mutation and an overall rare breakthrough in colorectal cancer treatment.
At Virginia Cancer Specialists we have dedicated Medical Oncologists who work on the cutting edge of colorectal cancer treatment and care. We have numerous clinical research studies to offer in the care of colorectal cancer patients. Participation in this KRAS mutation trial is just one example. Please reach out our team at Virginia Cancer Specialists if we can be of any help to you or your family.
* Adagrasib with or without Cetuximab in Colorectal Cancer with Mutated KRAS G12C – https://www.nejm.org/doi/full/10.1056/NEJMoa2212419
