The addition of BRAF-inhibitor vemurafenib to irinotecan and cetuximab chemotherapy treatment improves progression-free survival (PFS) for patients with BRAF-mutant metastatic colorectal cancer, according to a presentation at the Gastrointestinal Cancers Symposium.
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Approximately 7% of patients with metastatic colorectal cancer contain BRAFV600E mutations, which tend to be unresponsive to standard chemotherapy and consequently lower overall survival rates for those patients. The BRAF-inhibitor vemurafenib has shown limited success in treating BRAFV600E –specific tumors as a single agent or with cetuximab-based chemotherapy.
Researchers led by Scott Kopetz, MD, PhD, University of Texas MD Anderson Cancer Center, conducted a study to analyze the response rate of patients with BRAFV600E-mutant metastatic colorectal cancer after treatment with vemurafenib added to irinotecan and cetuximab. A total of 106 patients were randomly assigned to receive irinotecan (180 mg/m2 IV every 14 days) and cetuximab (500 mg/m2 IV every 14 days) with or without vemurafenib (960 mg orally twice daily). All patients had received 1 or 2 prior regimens with no anti-EHGR agents. Patients were permitted to crossover from the control arm to the vemurafenib arm if disease progression occurred. The primary endpoint was PFS.
Results of the study showed PFS was improved for the patients in the vemurafenib arm (HR = 0.42, 95% confidence interval [CI] of 0.26 to 0.66, P < .001). Median PFS for those in the vemurafenib arm (n = 54) was 4.4. months (95% CI: 3.6-5.7) compared to 2.0 months (95% CI: 1.8-2.1) for those in the control arm. Response rate was 16% versus 4% (P = .09) with a disease control rate of 67% versus 22% (P < .001), respectively. Approximately 50% of patients in the control arm crossed over to the vemurafenib arm at the time of progression, but overall survival and efficacy data for these patients were non-conclusive.
Grade III-IV adverse events such as anemia, neutropenia, and nausea were significantly higher in the vemurafenib arm. Higher rates of these adverse events may be attributed to increased duration of exposure and are similar to those seen in prior second-line studies of cetuximab plus irinotecan, according to the authors of the study.
Researchers concluded that irinotecan and cetuximab with vemurafenib treatment is effective in treating BRAFV600E – mutated metastatic colorectal cancer. “Overall novel therapies such as [vemurafenib] are needed for this rare and aggressive subset of colorectal cancer where our standard chemotherapy regimens are failing to provide substantial and meaningful clinical benefit,” Dr Kopetz said.
