Targeted combo therapies improve QoL, atop survival benefit for patients with BRAF+ CRC

In addition to survival benefit, the BEACON CRC trial has now shown that a targeted drug combination of encorafenib plus cetuximab with or without binimetinib led to longer maintenance of quality of life (QoL) for patients with BRAF V600E metastatic colorectal cancer (mCRC) compared with standard chemotherapy.

“Health-related QoL is an important component that really helps understand the patient experience and complements the clinical efficacy endpoints,” said Dr Scott Kopetz from the University of Texas MD Anderson Cancer Center in Texas, Houston, US during the 2020 Gastrointestinal Cancers Symposium (GICS).

“[The] intention of treatment is to improve survival while maintaining QoL, [which] is considered as one of the relevant factors for treatment selection by mCRC guidelines.”

Previously, improvements in the primary efficacy outcome of overall survival (OS; hazard ratio [HR], 0.52; p<0.0001) and objective response rate (ORR; 26 percent vs 2 percent; p<0.0001) with the triple-drug combination vs standard chemotherapy have been reported in the New England Journal of Medicine.

In the current secondary analysis, the patient-reported outcome of QoL was assessed using QLQ-C30, FACT-C, EQ-5D-5L, and PGIC*. The primary assessment for the various measures was the time to a definitive 10 percent deterioration in QoL. Subjects were 665 patients with BRAF V600E who were randomized 1:1:1 to receive either encorafenib plus cetuximab with (triplet regimen; n=224) or without binimetinib (doublet regimen; n=220), or a standard chemotherapy of irinotecan or FOLFIRI in addition to cetuximab (n=221) in the phase III, open-label trial. [N Engl J Med 2019;381:1632-1643]

Based on the EORTC QLQ-C30 Global Health Status, patients treated with the triplet or doublet regimen maintained their QoL for a longer time before reaching a 10 percent decline (median, 4.96 and 4.60 vs 2.20 months for triplet and doublet regimen vs standard chemotherapy, respectively). The corresponding risk reduction in QoL deterioration was 45 percent for the triplet regimen group (HR, 0.55, 95 percent confidence interval [CI], 0.43–0.70) and 44 percent for the doublet regimen group (HR, 0.54, 95 percent CI, 0.43–0.69). [GICS 2020, abstract 8]

Similarly, both the triplet and the doublet regimen groups saw a longer time to QoL deterioration on the FACT-C CRC subscale compared with the standard chemotherapy group (median, 5.65 and 5.36 vs 2.00 months; HR, 0.48, 95 percent CI, 0.38-0.62 and HR, 0.46, 95 percent CI, 0.36-0.59 for the triple and doublet regimen, respectively).

On the EQ-5D-5L visual analogue scale, the time to deterioration was also delayed for both the triplet (HR, 0.49, 95 percent CI, 0.38-0.63) and the doublet regimen groups (HR, 0.49, 95 percent CI, 0.39-0.63), compared with the standard chemotherapy group (median, 3.59 and 5.36 vs 2.37 months, respectively).

More than half of the patients receiving the triplet (53 percent) or the doublet regimen (58 percent) perceived at least a minimal improvement in symptoms as indicated on the PGIC, compared with 36 percent in the standard chemotherapy arm.  

There were no significant differences between the triplet and the doublet regimen groups in any of the QoL measures.

“In BEACON CRC, triplet and doublet demonstrated substantial improvement in patient-reported QoL assessments over the current standard of care in patients with BRAF V600E-mutant mCRC, ... a population with historically dismal outcomes,” concluded Kopetz.  

According to Kopetz, BRAF V600 mutation affects approximately 10 percent of the mCRC population.