Encorafenib regimens confer quality-of-life, survival benefit in BRAF V600E-mutant metastatic colorectal cancer
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A combination of encorafenib and cetuximab, with or without binimetinib, demonstrated significant improvement in patient-reported quality-of-life assessments compared with standard-of-care chemotherapy among patients with BRAF V600E-mutant metastatic colorectal cancer, according to results of the randomized phase 3 BEACON CRC study scheduled for presentation at Gastrointestinal Cancers Symposium.
Researchers also presented updated results for the study’s primary endpoint, showing similar survival results for the doublet and triplet regimens compared with standard-of-care chemotherapy.
“This represents a confirmation of the clinically meaningful benefit of the combinations compared with the control arm, and in my opinion represents a new standard of care for these patients,” Scott Kopetz, MD, PhD, FACP, professor of gastrointestinal medical oncology at The University of Texas MD Anderson Cancer Center, told Healio. “On the basis of this, a binimetinib application has not been submitted to the FDA, and the doublet is currently under review.”
Previous results of the BEACON CRC study showed the triplet regimen of encorafenib (Braftovi, Array Biopharma), binimetinib (Mektovi, Array Biopharma) and cetuximab (Erbitux, Eli Lilly) significantly improved OS (9 months vs. 5.4 months; P < .0001) and objective response rate (26% vs. 2%; P < .0001) compared with the current standard of care among patients with BRAF V600E metastatic colorectal cancer.
Kopetz and colleagues presented results of patient-reported quality-of-life assessments from the study, in which researchers randomly assigned 665 patients to the triplet regimen (n = 224), a doublet regimen of encorafenib and cetuximab (n = 220), or control regimen of irinotecan and cetuximab or FOLFIRI and cetuximab (n = 221).
Researchers assessed quality of life, a secondary endpoint of the study, at baseline and following each treatment cycle using the EORTC QOL Questionnaire (QLQ C30), Functional Assessment of Cancer Therapy Colon Cancer (FACT C), EuroQol 5D 5L and Patient Global Impression of Change (PGIC) validated measurement tools.
Time to 10% or greater deterioration between study groups, indicating a clinically meaningful reduction in quality of life, served as the primary assessment for the quality-of-life variables.
Results showed estimated reductions in the risk for quality-of-life deterioration of 45% (HR = 0.55; 95% CI, 0.43-0.7) based on QLQ C30 and 44% (HR = 0.56; 95% CI, 0.44-0.71) based on FACT C with the triplet vs. control regimen.
Those who received the doublet regimen had reductions in risk for quality-of-life deterioration of 46% (HR = 0.54; 95% CI, 0.43-0.69) based on QLQ C30 and 43% (HR = 0.57; 95% CI, 0.45-0.72) based on FACT C compared with the control regimen.
Researchers observed similar results with the EuroQol 5D 5L and PGIC assessments, and no overall differences in quality of life between the triplet and doublet regimens across all four assessments.
Additionally, updated results of OS — the primary endpoint of the BEACON CRC study — showed that the doublet and triplet groups both conferred median OS of 9.3 months compared with 5.9 months in the control group.
Updated response rates were 27% in the triplet group, 20% in the doublet group and 2% in the control group.
“The quality of life was maintained longer for patients treated with the doublet or triplet compared with the control, with higher rates of symptomatic improvements on treatment with either the doublet or triplet,” Kopetz said. “There were no new safety signals seen.” – by John DeRosier
Reference:
Kopetz S, et al. Abstract 8. Presented at: Gastrointestinal Cancers Symposium; Jan. 23-25, 2020; San Francisco.
Disclosures: Pfizer Inc. funded this study. Kopetz reports consultant/advisory roles with Amal Therapeutics, Amgen, AstraZeneca, Bayer Health, Biocartis, Boehringer Ingelheim, Boston Biomedical, EMD Serono, Eli Lilly, Genentech, Holy Stone Healthcare, Karyopharm Therapeutics, Merck, Navire Pharma, Novartis, Pierre Fabre and Redx Pharma; stock ownership in MolecularMatch and Navire Pharma; and institutional research funding from Amgen, Array BioPharma, Biocartis, Eli Lilly, EMD Serono, Genentech/Roche, MedImmune, Novartis and Sanofi. Please see the abstract for all other authors’ relevant financial disclosures.
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Marwan Fakih, MD
The OS results of this study — presented in September at European Society of Medical Oncology Congress — showed an improvement in favor of the experimental arms, so we already had a good sense that this was going to change the standard for this subset of patients.
The updated OS results presented at this meeting were interesting because they showed the doublet group also fared quite well compared with the triplet group. Both regimens showed significant HR benefits, which was exciting for these patients even though the survival was a median 9.3 months.
The updated OS results don’t show a statistically significant difference between the double and triplet groups; therefore, the registration path has moved over to the doublet, and the triplet regimen will no longer be pursued as there is no reason to use three drugs over two if they don’t have significant differences in outcome.
Also, excitingly, these data show both the doublet and triplet regimens improved quality-of-life measurements among these patients.
As a patient’s cancer progresses, quality of life worsens. This is true even with therapy because the treatment will not control the disease indefinitely or because of treatment-related toxicities. This study showed that the doublet decreased the time to deterioration by 46% compared with cetuximab in combination with irinotecan, meaning it’s taking almost double the time for quality of life to deteriorate for these patients compared with those on the standard therapy.
These data overall are very meaningful and are sufficient to make the doublet regimen a standard for these patients. The OS is probably enough on its own, but the quality-of-life data give us extra assurance that this treatment is justified.
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