Most Read Articles
Dr Margaret Shi, 13 Jul 2020

An MRI-first diagnostic pathway, combined with risk-tailored screening, is shown to improve the benefit-to-harm profile and cost-effectiveness of screening for prostate cancer (PCa), according to results of a recent lifetable modelling study presented at AACR 2020 Virtual Meeting II.

Christina Lau, 14 Jul 2020

Flat-dose nivolumab, administered as a 30-minute infusion, is well tolerated and active in Asian patients with previously treated advanced non-small-cell lung cancer (NSCLC), according to results of the phase IIIb CheckMate 870 study.

Natalia Reoutova, 17 Jul 2020

At a median follow-up of 22.9 months, atezolizumab plus carboplatin and etoposide (CP/ET), given as a first-line treatment, continued to demonstrate an improvement in overall survival (OS) vs placebo plus CP/ET in patients with extensive-stage small-cell lung cancer (ES-SCLC), according to updated results of the IMpower133 trial presented at the American Association for cancer Research (AACR) 2020 Virtual Annual Meeting II.

12 Jun 2020
Drawing from experience as a key investigator in landmark clinical trials (including PALOMA, MONALEESA and MONARCH), and his clinical experience with CDK4/6 inhibitors, Dr Rafael Villanueva Vázquez shares his insights into the current evidence of using CDK4/6 inhibitors to treat HR+/HER2- ABC.

Triplet regimen of encorafenib, binimetinib and cetuximab extends survival in BRAF V600E-mutated mCRC

Dr Margaret Shi
14 Nov 2019

The triplet regimen of encorafenib, binimetinib and cetuximab provides significant and clinically relevant benefits in overall survival (OS) and objective response rate (ORR) in patients with BRAFV600E-mutated metastatic colorectal cancer (mCRC) who experience disease progression after one or two previous regimens, according to results of an interim analysis of the BEACON CRC trial.

After a median follow-up of 7.8 months, patients randomized to receive triplet therapy had a significant improvement in OS compared with the control group of patients who received investigators’ choice of either cetuximab plus irinotecan or cetuximab plus FOLFIRI (folinic acid, 5-FU and irinotecan) (median, 9.0 months vs 5.4 months; hazard ratio [HR], 0.52; 95 percent confidence interval [CI], 0.39 to 0.70; p<0.01), with consistent results demonstrated in subgroup analyses. Median OS of patients who received doublet therapy with encorafenib plus cetuximab vs the control group was 8.4 months vs 5.4 months (HR, 0.60; 95 CI, 0.45 to 0.79; p<0.001). [N Engl J Med 2019;381:1632-1643]

ORR based on independent review was also significantly increased with the triplet regimen compared with the control regimen (26 percent vs 2 percent; p<0.001).

Likewise, PFS was improved in the triplet-therapy group compared with the doublet-therapy group and the control group (median, 4.3 months vs 4.2 months vs 1.5 months; HR, 0.38; 95 percent CI, 0.29 to 0.49) after a median follow-up of 5.4 months.

The BECAON CRC trial was a global, multicentre, randomized, open-label, phase III trial, in which 665 patients were randomized (1:1:1) to receive triplet therapy (n=224), doublet therapy (n=220), or investigators’ choice of a control regimen (n=221).

The median duration of exposure to trial treatment was 21 weeks, 19 weeks and 7 weeks in the triplet-therapy group, doublet-therapy group and the control group, respectively.

The BRAFV600E mutation occurs in approximately 10 percent of patients with mCRC. Initial standard chemotherapy for BRAFV600E-mutated CRC is known to be associated with poor outcomes. The triplet regimen evaluated in the trial was designed to provide maximum inhibition of the mitogen-activated protein kinase (MAPK) pathway. Previous studies have shown promising activity of encorafenib in combination with cetuximab compared with triplet regimens of an anti-EGFR agent with a BRAF inhibitor plus either a MEK inhibitor or irinotecan. [J Clin Oncol 2017; 35:Suppl:3505; Cancer Discov 2018;8:428-443; J Clin Oncol 2016;34:3544-3544]

Although the current trial was not powered to compare the triplet regimen with the doublet regimen directly, a benefit in OS was demonstrated with the triplet therapy compared with the doublet therapy (HR, 0.79; 95 percent CI, 0.59 to 1.06).

Adverse events (AEs) of grade 3 or above occurred at similar rates across all treatment groups (58 percent vs 50 percent vs 61 percent), with gastrointestinal-related and skin-related events being the most common AEs in the triplet-therapy group. The AE profiles of both combination regimens allowed the maintenance of a high dose intensity for the majority of patients, and were consistent with the known AE profile of each agent.

“Further follow-up is needed to better define the relative benefits of the triplet and doublet regimens,” added the authors.

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Most Read Articles
Dr Margaret Shi, 13 Jul 2020

An MRI-first diagnostic pathway, combined with risk-tailored screening, is shown to improve the benefit-to-harm profile and cost-effectiveness of screening for prostate cancer (PCa), according to results of a recent lifetable modelling study presented at AACR 2020 Virtual Meeting II.

Christina Lau, 14 Jul 2020

Flat-dose nivolumab, administered as a 30-minute infusion, is well tolerated and active in Asian patients with previously treated advanced non-small-cell lung cancer (NSCLC), according to results of the phase IIIb CheckMate 870 study.

Natalia Reoutova, 17 Jul 2020

At a median follow-up of 22.9 months, atezolizumab plus carboplatin and etoposide (CP/ET), given as a first-line treatment, continued to demonstrate an improvement in overall survival (OS) vs placebo plus CP/ET in patients with extensive-stage small-cell lung cancer (ES-SCLC), according to updated results of the IMpower133 trial presented at the American Association for cancer Research (AACR) 2020 Virtual Annual Meeting II.

12 Jun 2020
Drawing from experience as a key investigator in landmark clinical trials (including PALOMA, MONALEESA and MONARCH), and his clinical experience with CDK4/6 inhibitors, Dr Rafael Villanueva Vázquez shares his insights into the current evidence of using CDK4/6 inhibitors to treat HR+/HER2- ABC.