BEACON CRC
A Multicenter, Randomized, Open-label, 3-Arm Phase 3 Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan/Cetuximab or Infusional 5-Fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer
Phase 3N = 665NCT02928224
- Population
- BRAF V600E-mutated metastatic colorectal cancer with disease progression after one or two previous regimens
- Design
- Open-label, randomised phase 3 trial with 1:1:1 allocation to triplet therapy, doublet therapy or an investigator-chosen control. The primary endpoints were overall survival and objective response rate for triplet versus control; overall survival for doublet versus control was a secondary endpoint (a key secondary endpoint in the 2021 update). The 2019 report is a prespecified interim analysis; the 2021 report adds six months of follow-up and objective response for all randomised patients.
- Primary endpoint
- OS, ORR
- Arms
- Cetuximab with irinotecan or FOLFIRI (control, n = 221): Investigator's choice of cetuximab plus irinotecan, or cetuximab plus FOLFIRI
- Encorafenib + cetuximab (experimental, n = 220): Encorafenib plus cetuximab
- Encorafenib + binimetinib + cetuximab (experimental, n = 224): Encorafenib plus binimetinib plus cetuximab
- People
- Kopetz S, senior author Tabernero J
OSHR 0.52 (95% CI 0.39–0.70)Δ median OS+3.6 monthsOSHR 0.60 (95% CI 0.45–0.79)Δ ORR+24 pointsOSHR 0.60 (95% CI 0.47–0.75)Δ median OS+3.4 months
Show the numbers
| Endpoint | Analysis | Encorafenib + cetuximab / Encorafenib + binimetinib + cetuximab | Cetuximab with irinotecan or FOLFIRI | Effect |
|---|---|---|---|---|
| OSAll randomised patients (analysis population not stated in the abstract)Overall survival, triplet versus control (primary endpoint) | interimKopetz 2019 | median 9 months | median 5.4 months | HR 0.52 (95% CI 0.39–0.70)P<0.001Prespecified interim analysis reported in the 2019 paper. |
| OSAll randomised patients (analysis population not stated in the abstract)Overall survival, doublet versus control (secondary endpoint in this report) | interimKopetz 2019 | median 8.4 months | — | HR 0.60 (95% CI 0.45–0.79)P<0.001The abstract gives the doublet median and the hazard ratio versus control but no separate control median for this comparison. |
| ORRAll randomised patients (analysis population not stated in the abstract)Confirmed response rate, triplet versus control (primary endpoint) | interimKopetz 2019 | 26% (18–35%) | 2% (0–7%) | P<0.001The abstract does not report a response rate for the doublet at this analysis. |
| OSAll randomised patients (analysis population not stated in the abstract)Overall survival, triplet versus control | long term-updateTabernero 2021 | median 9.3 months (8.2–10.8) | median 5.9 months (5.1–7.1) | HR 0.60 (95% CI 0.47–0.75)Updated analysis with six months of additional follow-up (2021 paper); the authors describe it as a descriptive post hoc analysis with no formal hypothesis tests. |
| OSAll randomised patients (analysis population not stated in the abstract)Overall survival, doublet versus control (key secondary endpoint) | long term-updateTabernero 2021 | median 9.3 months (8.0–11.3) | median 5.9 months (5.1–7.1) | HR 0.61 (95% CI 0.48–0.77)Updated analysis with six months of additional follow-up (2021 paper); the authors describe it as a descriptive post hoc analysis with no formal hypothesis tests. The control median is the one the abstract reports beside the triplet comparison. |
| ORRAll randomised patients (the 2021 abstract reports ORR for all randomised patients)Confirmed objective response rate, all randomised patients | long term-updateTabernero 2021 | 26.8% (21.1–33.1%) | 1.8% (0.5–4.6%) | Reported by blinded central review in the 2021 abstract (Purpose); no p-value is given in the abstract. |
| Endpoint | Analysis | Encorafenib + cetuximab / Encorafenib + binimetinib + cetuximab | Cetuximab with irinotecan or FOLFIRI | Effect |
|---|---|---|---|---|
| OSAll randomised patients (analysis population not stated in the abstract)Overall survival, triplet versus control (primary endpoint) | interimKopetz 2019 | median 9 months | median 5.4 months | HR 0.52 (95% CI 0.39–0.70)P<0.001Prespecified interim analysis reported in the 2019 paper. |
| OSAll randomised patients (analysis population not stated in the abstract)Overall survival, doublet versus control (secondary endpoint in this report) | interimKopetz 2019 | median 8.4 months | — | HR 0.60 (95% CI 0.45–0.79)P<0.001The abstract gives the doublet median and the hazard ratio versus control but no separate control median for this comparison. |
| ORRAll randomised patients (analysis population not stated in the abstract)Confirmed response rate, triplet versus control (primary endpoint) | interimKopetz 2019 | 26% (18–35%) | 2% (0–7%) | P<0.001The abstract does not report a response rate for the doublet at this analysis. |
| OSAll randomised patients (analysis population not stated in the abstract)Overall survival, triplet versus control | long term-updateTabernero 2021 | median 9.3 months (8.2–10.8) | median 5.9 months (5.1–7.1) | HR 0.60 (95% CI 0.47–0.75)Updated analysis with six months of additional follow-up (2021 paper); the authors describe it as a descriptive post hoc analysis with no formal hypothesis tests. |
| OSAll randomised patients (analysis population not stated in the abstract)Overall survival, doublet versus control (key secondary endpoint) | long term-updateTabernero 2021 | median 9.3 months (8.0–11.3) | median 5.9 months (5.1–7.1) | HR 0.61 (95% CI 0.48–0.77)Updated analysis with six months of additional follow-up (2021 paper); the authors describe it as a descriptive post hoc analysis with no formal hypothesis tests. The control median is the one the abstract reports beside the triplet comparison. |
| ORRAll randomised patients (the 2021 abstract reports ORR for all randomised patients)Confirmed objective response rate, all randomised patients | long term-updateTabernero 2021 | 26.8% (21.1–33.1%) | 1.8% (0.5–4.6%) | Reported by blinded central review in the 2021 abstract (Purpose); no p-value is given in the abstract. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.52 | 0.39–0.7 |
| OS | 0.6 | 0.45–0.79 |
| OS | 0.6 | 0.47–0.75 |
| OS | 0.61 | 0.48–0.77 |
- Encorafenib + binimetinib + cetuximab (experimental)
- Cetuximab with irinotecan or FOLFIRI (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Encorafenib + binimetinib + cetuximab | Cetuximab with irinotecan or FOLFIRI |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 6 | 63.0% | 46.3% |
| 11 | 42.9% | 24.4% |
| 17 | 27.0% | 11.3% |
| 23 | 17.0% | 5.2% |
- Encorafenib + cetuximab (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Encorafenib + cetuximab |
|---|---|
| 0 | 100.0% |
| 5 | 66.2% |
| 11 | 40.3% |
| 16 | 26.7% |
| 21 | 17.7% |
Appears in
Sources
Kopetz S, Grothey A, Yaeger R, Van Cutsem E, Desai J, Yoshino T, et al. Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer. N Engl J Med. 2019;381(17):1632-1643.
Tabernero J, Grothey A, Van Cutsem E, Yaeger R, Wasan H, Yoshino T, et al. Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated BRAF V600E-Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study. J Clin Oncol. 2021;39(4):273-284.