Predicting recurrence in CRC using post-operative circulating tumour DNA
September 2023 Circulating tumour DNA (ctDNA) refers to the fragmen [...]
READ MOREASCO 2022
June 2022.
Key Updates from ASCO 2022
1. Immunotherapy treatment results in an “unprecedented” clinical complete response in 100% of first 14 patients with rectal cancer
In a study of patients with locally advanced mismatch repair-deficient (dMMR) rectal cancer, 6 months of treatment with the immunotherapy agent dostarlimab-gxly alone led to a clinical complete response (the absence of all detectable cancer) in 100% of the study’s first 14 patients. Currently, the standard treatment for locally advanced rectal cancer involves treatment with chemotherapy and radiation followed by surgery to remove the rectum. With the experimental treatment, none of the patients have had to undergo treatment with chemotherapy, radiation, or surgery, and there were no grade 3 or 4 adverse events experienced by the patients. By eliminating the need for standard therapies, patients are spared the significant risk of morbidities such as urinary, sexual, and defecatory dysfunction that are associated with these treatments.
Though the patients have been followed for an average of only 6.8 months, four patients have been followed for nearly 2 years, and only four have received less than 6 months of the required treatment. In dMMR rectal cancer, the use of PD-1 inhibitors like dostarlimab-gxly may be a potential treatment to replace some or even all the standard of care treatments currently in place to treat rectal cancer – chemotherapy, chemotherapy plus radiation, or chemotherapy, radiation and surgery. The researchers caution, however, that the study population is small and therefore these findings must be replicated in larger populations with longer follow-up before any definitive changes to the standard of care treatment can be made.
2. Use of ctDNA to identify need for adjuvant therapy in stage II colon cancer
Results from the phase II DYNAMIC trial demonstrated that adjuvant (post-operative) chemotherapy could be omitted for patients with stage II colon cancer who did not show detectable levels of circulating tumour DNA (ctDNA) in the blood without compromising recurrence-free survival. For patients with ctDNA present in the blood after surgery, the rate of cancer recurrence was low among those that did receive adjuvant chemotherapy, suggesting a survival benefit from the additional treatment with chemotherapy.
ctDNA is a tool that can detect minimal residual disease, or very small amounts of remaining cancer cells after surgery. This can be used to better predict a patient’s risk for disease recurrence and selection of specific patients who are most likely to benefit from additional adjuvant therapy.
The DYNAMIC study findings are encouraging because they show that with adjuvant therapy, ctDNA-positive patients can receive significant benefit from the additional chemotherapy. Next steps including a randomized trial assigning ctDNA-positive and ctDNA-negative patients to adjuvant treatment vs. no treatment, to provide more conclusive evidence of the impact or lack of impact in the two patient subsets.
3. Panitumumab plus mFOLFOX6 improves Overall Survival in left-sided RAS wild-type mCRC
Findings from the PARADIGM phase III study showed that the use of the targeted therapy panitumumab plus the chemotherapy regimen mFOLFOX6 (5-FU, folinic acid, oxaliplatin) significantly improved overall survival of patients with metastatic colorectal cancer (mCRC) tumours identified as RAS wild-type that originated on the left-side of the colon. Patients were randomly assigned to receive panitumumab plus mFOLFOX6, or bevacizumab plus mFOLFOX6. Patients who received panitumumab had an overall survival of 37.9 months vs 34.4 months for those who received bevacizumab, and experienced a 18% lower risk of death.
These findings highlight the important of early molecular profiling of tumours to select the optimal treatment option for patients at the right time. If a tumour is RAS wild-type and originates on the left-side of the colon, the study findings suggest that initial treatment with panitumumab plus mFOLFOX6 is superior to first-line treatment with bevacizumab plus mFOLFOX6.
