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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.
Data reported at the ESMO World Congress on Gastrointestinal Disorders
Cancer 2019, (2) suggest that encorafenib, a combination of three drugs,
binimetinib and cetuximab should replace chemotherapy for
seven patients with metastatic colorectal cancer and carriers of a BRAF factor
mutation.
"These are very exciting results because we are trying to target
Colorectal cancer mutant BRAF for many years. It's encouraging to see
such a significant improvement in overall survival and response in
patients with such aggressive tumor biology. Hope this will be soon
lead to increased access to this treatment for patients with
need, "said Dr. Scott Kopetz, author of the study,
UT MD Anderson Cancer Center, Houston, USA.
Kopetz explained that the combination of three drugs relies on growth
understanding of the activation of cancer genes such as BRAF and the
effects of targeted therapies. "Colorectal cancer does not respond to
BRAF treatment 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.
Commenting on the relevance of the new data, Professor Andres Cervantes
from the Institute of Biomedical Research INCLIVA, University of Valencia,
Spain stressed that it would be important for all patients
colorectal cancer to be tested for BRAF mutations in light 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
better than the previous treatment, it is therefore essential that patients be
tested regularly. "
He also pointed to the chemotherapy-free nature of the target
combination used in the study. "In many other types of cancer, and
especially in colorectal cancer, it is common for targeted biological diseases.
therapies for use in combination with chemotherapy. The fact that we
can give this targeted combination without requiring chemotherapy is
very good news for patients, especially because of the side effects
they usually have chemotherapy, "he added.
"Currently, targeted therapies should probably be limited to
group of patients treated in the BEACON CRC trial who had progressed after the
one or two previous lines of chemotherapy. However, it is important that
we are studying its use in other settings where more patients with BRAF
mutations can also benefit, including those with less advanced disorders.
metastatic disease and possibly in 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 that progressed after one or two
previous regimes in the metastatic setting were randomized to receive
triplet, doublet (encorafenib and cetuximab) or treatment
choice of 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 versus 5.4 months (95%
IC: 4.8, 6.6) for standard treatment (risk ratio [HR] 0.52; 95% CI:
0.39, 0.7, p <0.0001).
Objective response rate confirmed by the central blind review for the
The targeted triplet therapy was 26% (95% CI: 18.35), compared to 2% (95%).
IC: 0.7, p <0.0001) for the standard treatment.
The median overall survival for 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 triplets and
doublet therapies, but future badyzes will explore which patients are
likely to benefit from triplet versus doublet combinations.
Targeted treatment with BRAF V600E was well tolerated, with Grade 3 or higher
higher adverse effects observed in 58% of patients under triplet, 50%
those of the doublet group and 61% of those of the standard treatment
group.
An ongoing study (ANCHOR-CRC) is studying the effects of
triplet treatment as first-line therapy in patients with metastases
Colorectal cancer mutant BRAF V600E.
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