The combination of targeted therapies is effective in patients with bowel cancer

New data presented at ESMO show that targeted therapeutic combinations work in patients with bowel cancer

New data has shown for the first time that a combination of targeted therapies can improve survival in patients with advanced bowel cancer.

The results of the BEACON CRC phase III trial showed that triple therapy targeting BRAF mutations in progressive metastatic colorectal tumors significantly improved overall survival and objective response compared to conventional care. (1)

The data, reported at the 2018 ESMO World Congress on Gastrointestinal Cancer, (2) suggest that encorafenib, binimetib, and cetuximab, a combination of three drugs, should replace chemotherapy at home. one in seven patients with metastatic colorectal cancer and BRAF gene mutation.

"These results are very interesting 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. Hopefully this will soon lead to better access to this treatment for patients for whom there is currently such a high need, "said Dr. Scott Kopetz, study author, UT MD Cancer Center Anderson, Houston , United States.

"In many other types of cancer, and particularly in colorectal cancer, it is common for targeted biologic therapies to be used in combination with chemotherapy."

Kopetz explained that the combination of three drugs is based on a growing understanding of the activation of cancer genes such as BRAF and the effects of targeted therapies. "Colorectal cancer does not respond to treatment with BRAF alone because the tumor cells adapt by other mechanisms after the initial treatment. With this triple targeted therapy, we use a very scientifically logical combination to inhibit BRAF and these other mechanisms, "he said.

Professor Andres Cervantes, from the INCLIVA Institute for Biomedical Research, University of Valencia (Spain), stressed the relevance of the relevance of the new data. It will be important for all patients with colorectal cancer to be tested for BRAF mutations in light of the data. the results of BEACON CRC. "We now have a specific treatment that can change the natural course of the disease in patients with BRAF mutations and that is better than the previous treatment, so it is essential that patients undergo routine tests."

He also emphasized the chemo-free nature of the targeted combination used in the study. "In many other types of cancer, and particularly in colorectal cancer, it is common for targeted biologic therapies to be used in combination with chemotherapy. The fact that we can give this targeted combination without the need for chemotherapy is very good news for patients, particularly because of the side effects they usually experience with chemotherapy, "he added.

"At present, targeted therapy should probably be limited to the group of patients treated in the BEACON CRC trial who had progressed after one or two previous lines of chemotherapy. However, it is important that we examine its use in other settings where more patients with BRAF gene mutations may also benefit, including those with less advanced metastatic disease and possibly in the context of adjuvant after primary curative surgery, "concluded Cervantes.

Results of the study

In the BEACON CRC Global Study (NCT02928224), 665 patients with BRAF V600E mutant colorectal cancer and progressing after one or two previous metastatic treatment regimens were randomized to receive triplet treatment, a treatment with doublet (encorafenib and cetuximab) or the choice of the investigator. irinotecan or folinic acid, fluoruracil and irinotecan (FOLFIRI) and cetuximab.

Median overall survival was 9 months (95% confidence interval) [CI]: 8, 11.4) for targeted triplet treatment vs. 5.4 months (95% CI: 4.8, 6.6) for standard treatment (risk ratio [HR] 0.52; 95% CI: 0.39, 0.7, p <0.0001).

The objective response rate confirmed by the blinded central review 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 of the doublet combination was 8.4 months (95% CI: 7.5, 11) compared to standard treatment (HR 0.6, 95% CI: 0.45, 0.79, p <0.0003). The study was not designed to compare triplet and doublet therapies, but future badyzes will explore the patients most likely to benefit from triplet versus doublet combinations.

Targeted treatment with BRAF V600E was well tolerated; Grade 3 or greater adverse events were observed in 58% of patients receiving triplet, 50% of those in the doublet group and 61% of those in the standard treatment group.

An ongoing study (ANCHOR-CRC) is studying the effects of triplet therapy as a first-line treatment in patients with metastatic colorectal cancer BRAF V600E.