Encorafenib in Combination With Cetuximab After Systemic Therapy in Patients With BRAFV600E Mutant Metastatic Colorectal Cancer: German Health Technology Assessment-Driven Analyses From the BEACON CRC Study

The German Health Technology Assessment (HTA) helps the clinician by giving an additional evaluation of the clinical evidence of a substance in the light of a risk benefit assessment. In the HTA a hint for a considerable additional benefit of encorafenib + cetuximab compared to the ACT in BRAFV600E-mutant mCRC patients was granted. This treatment is considered the new standard of care for these patients. Background: Purpose of this analysis was to report data of the BEACON CRC trial used in the German Health Technology Assessment (HTA) and previously unpublished data focusing on the dual blockade (encorafenib + cetuximab) and appropriate comparative therapy (ACT/control: cetuximab + irinotecan-based chemotherapy) of patients with BRAF(V600E)-mutant mCRC. Materials and Methods: Analyses included overall survival (OS) and time-to-event analyses of morbidity and safety. Results: A total of 220 patients received encorafenib + cetuximab and 221 patients ACT/control. Median OS was 9.3 (encorafenib + cetuximab) versus 5.9 months (ACT/control) (stratified hazard ratio (HRstrat): 0.61 [95% confidence interval: 0.48-0.77]). Time-to-response (TTR) showed a statistically significant advantage for encorafenib + cetuximab compared to ACT/control (HRstrat [95% CI]: 10.46 [3.75; 29.15]; P < .0001). Median progression-free survival 2, ie, PFS after initiation of subsequent treatment after completion of study treatment, was 8.3 (dual blockade) versus 5.3 months (ACT/control), representing a statistically significant benefit for the dual blockade (HRstrat [95% CI]: 0.62 [0.48; 0.78]; P < .0001). The statistically significant advantage for diarrhea (EORTC QLQ-C30) reached clinical relevance (LS-mean [95% CI]; P-value / Hedges'g [95% CI]: -12.61 [-17.75; -7.47]; P < .0001 / -0.53 [-0.74; -0.31]). The time-to-event analyses showed a statistically significant benefit for the dual blockade for serious adverse events (AE), severe AEs and AEs leading to discontinuation. Conclusion: In the HTA, the German G-BA granted a hint for a considerable additional benefit of encorafenib + cetuximab compared to the ACT in BRAF(V600E)-mutant mCRC patients. This treatment is considered the new standard of care for these patients. (C) 2022 The Authors. Published by Elsevier Inc.

Automated summary

The German Health Technology Assessment (HTA) indicates that encorafenib + cetuximab has a significant additional benefit for patients with BRAFV600E-mutant mCRC and is considered the new standard of care for these patients.