Targeted therapy improves survival of patients with advanced bowel cancer



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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.

The data, reported at the 2018 ESMO World Congress on Gastrointestinal Cancer, suggest that encorafenib, binimetib, and cetuximab, a combination of three drugs, are expected to replace the chemotherapy of the drug. one of seven patients with metastatic colorectal cancer and BRAF mutation carriers.

"These results are very interesting because we have been trying to target colorectal BRAF mutant cancer for many years, and it is encouraging to see such a significant improvement in the overall survival and response of patients with such aggressive tumor biology. will lead soon to increase access to this treatment for those patients for whom there is currently so much unmet need, "said Dr. Scott Kopetz, author of the study, UT MD Anderson Cancer Center, Houston, USA. United.

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 BRAF therapy 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, especially colorectal cancer, it is common for targeted biologic therapies to be badociated with chemotherapy, and the fact that we can provide this targeted combination without the need for chemotherapy is very good news for us. patients, especially because of the side effects they usually feel with chemotherapy, "he added.

"At this time, targeted treatment should probably be limited to the group of patients treated in the BEACON CRC trial that had progressed after one or two previous lines of chemotherapy." However, it is important that we review its use in other settings where more patients with BRAF mutations may also benefit, including those with less advanced metastatic disease and possibly in the adjuvant setting 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.

Reference: LBA-006 & # 39; BEACON CRC: a randomized, 3-arm, phase 3 study of encorafenib and cetuximab with or without binimetib, versus choice of irinotecan or FOLFIRI plus cetuximab in the treatment of BRAF V600E mutant metastatic colorectal cancer – will be presented by Scott Kopetz during Session XX: Colorectal Cancer (Part I) on Saturday, July 6 from 9:20 am to 8:05 pm (Paris time). Annals of Oncology 30 (Supplement 4): iv137 – iv151, 2019

This article has been republished from the following materials. Note: Content may have changed for length and content. For more information, please contact the cited source.

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