Targeted therapy combination improves survival in patients with advanced bowel cancer
ESMO World Congress on Gastrointestinal Cancer 2019, Barcelona, Spain, July 3-6
New data have shown for the first time that a combination of targeted therapies can improve the survival of patients with advanced bowel cancer. The results of the BEACON CRC Phase III study showed that triple therapy targeting BRAF mutations in progressive metastatic colorectal tumors significantly improves overall survival and objective response compared to standard care.
The data, reported at the 2019 ESMO World Congress on Gastrointestinal Cancer, suggest that the combination of three drugs, encorafenib, binimetinib and cetuximab, should replace chemotherapy for one in seven patients with metastatic colorectal cancer with a BRAF mutation.
"These are very exciting results because we have been trying to target BRAF mutant colorectal cancer for many years. It is encouraging to see such a significant improvement in overall survival and response in patients with such aggressive tumor biology. Let's hope that this will soon lead to increased access to this treatment for patients with such a large unmet need," said Dr. Scott Kopetz, author of the study, from the UT MD Anderson Cancer Center, Houston, USA.
Mr. Kopetz explained that the combination of three drugs is based on a better understanding of the activation of cancer genes such as BRAF and the effects of targeted therapies. "Colorectal cancer does not respond only to BRAF treatment, because tumour cells adapt by other mechanisms after initial treatment. With this targeted triple therapy, we are using a very scientifically logical combination to inhibit BRAF and these other mechanisms," he said.
Andres Cervantes from the INCLIVA Biomedical Research Institute, University of Valencia, Spain, stressed that it will be important that all patients with colorectal cancer be tested for BRAF mutations in the light of the results of the BEACON CRC. "We now have a specific treatment that can change the natural course of the disease in patients with BRAF mutations and is better than the previous treatment, so it is essential that patients are systematically tested."
He also highlighted the chemotherapy-free nature of the targeted combination used in the study. "In many other types of cancer, particularly colorectal cancer, targeted biological treatments are often used in combination with chemotherapy. The fact that we can give this targeted combination without chemotherapy is very good news for patients, especially because of the side effects they usually experience with chemotherapy," he added.
"At this time, the targeted treatment should probably be limited to the group of patients treated in the BEACON CRC study who have progressed after one or two previous chemotherapies. However, it is important that we study its use in other settings where more patients with BRAF mutations could also benefit, including those with less advanced metastatic disease and possibly in an adjuvant setting after primary surgery with curative intent," concludes Cervantes.
Results of the study
In the global study BEACON CRC (NCT02928224), 665 patients with BRAF V600E mutant colorectal cancer who had progressed after one or two previous treatments in metastatic conditions were randomized to receive triplet, doublet (encorafenib and cetuximab) or irinotecan or folinic acid, fluoruracil and irinotecan (FOLFIRI) and cetuximab treatment.
Median overall survival was 9 months (95% confidence interval[CI]: 8.11.4) for targeted triplet treatment compared to 5.4 months (95% CI: 4.8, 6.6) for standard treatment (hazard ratio[HR] 0.52; 95% CI: 0.39, 0.7, p<0.0001).
The objective response rate confirmed by central blinded examination for targeted triplet treatment was 26% (95% CI: 18, 35) compared to 2% (95% CI: 0.7, p<0.0001) for standard treatment.
The median overall survival for the diplet combination was 8.4 months (95% CI: 7.5, 11) compared to standard treatment (95% CI: 0.45, 0.79, p<0.0003). The study was not designed to compare triplet and doublet therapies, but future analyses will examine which patients are most likely to benefit from triplet combinations versus doublet combinations.
The targeted treatment with BRAF V600E was well tolerated, with grade 3 or higher adverse events observed in 58% of patients treated with triplet, 50% of those in the doublet group and 61% of those in the standard treatment group.
An ongoing study (ANCHOR-CRC) is investigating the effects of triple therapy as a first-line treatment in patients with metastatic mutant colorectal cancer BRAF V600E.
