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Multiple clinical trials are currently exploring new therapies for patients with metastatic colorectal cancer (mCRC). The fluoropyrimidine drug TAS-102 has shown third-line efficacy in a randomized, blinded, placebo-controlled study, Heinz-Josef Lenz, MD, states. These results are especially promising, since many of these patients have been previously treated with fluoropyrimidines. Moreover, it was recently announced that TAS-102 significantly improved overall survival (OS) in a phase III trial for patients with heavily pretreated mCRC.
Several approaches are being evaluated for delivery of the active metabolite of irinotecan SN-38, including liposomal SN-38 and antibody-linked SN-38; however, these drugs are very early in development, notes Marwan Fakih, MD.
The PPAR gamma inhibitor CS7017 showed promise in early-phase studies. However, a recent trial of CS7017 in combination with FOLFIRI showed insufficient efficacy, according to John Marshall, MD.
Patients with BRAF
-mutated mCRC seem to benefit the most from combination targeted therapy, Johanna Bendell, MD, believes. Although patients with BRAF
mutations make up 8% to 10% of the patient population, these patients tend to have a much poorer prognosis overall.
With single-agent BRAF inhibitor therapy, Bendell notes that the colon cancer manages to circumvent the blockade. Combination therapy with a BRAF inhibitor and a MEK inhibitor has shown improved response rates. Adding to this, double combination therapy, which includes an EGFR inhibitor plus a BRAF inhibitor, and triple combination regimens, which include an EGFR inhibitor, a BRAF inhibitor, and a MEK inhibitor, may soon be on the horizon.