Comparing Stivarga and Lonsurf in Metastatic Colorectal Cancer

Patients with metastatic colorectal cancer now have more treatment options than ever, explains Tanios Bekaii-Saab, M.D. 
Recent advancements have drastically changed the treatment options for patients with metastatic colorectal cancer (mCRC), according to Tanios Bekaii-Saab, M.D.

“We used to run out of options,” said Bekaii-Saab, a professor of Medicine at Mayo Clinic. “Now patients go through two or three lines of therapy, depending on whether they have a mutation in RAS or not. We now have multiple options available to us, including regorafenib (Stivarga) and TAS-102 (Lonsurf).”

The FDA approved Lonsurf in September 2015 for the treatment of patients with mCRC who have previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, as well as an anti-VEGF biologic product and an anti-EGFR monoclonal antibody, if RAS wild-type.

The approval was based on the phase 3 RECOURSE trial, which demonstrated a median overall survival (OS) for patients with mCRC who received Lonsurf of 7.1 months compared with 5.3 months with placebo. The median progression-free survival (PFS) in the Lonsurf arm was two months versus 1.7 months with placebo.
Stivarga was approved by the FDA in September 2012 for patients with mCRC, based on the randomized phase 3 CORRECT trial, which showed a significant improvement in OS in patients who received treatment with Stivarga.

Findings from the phase 3 CONCUR trial confirmed that Stivarga improves survival when compared with placebo in patients with pretreated mCRC, demonstrating a median OS of 8.8 months for patients who received Stivarga versus 6.3 months for patients who received placebo. Median PFS was 3.2 versus 1.7 months, with Stivarga and placebo, respectively.

Despite these successes, many questions still remain regarding Stivarga and Lonsurf in mCRC, according to Bekaii-Saab. In an interview with CURE, he compared the mechanisms of action and toxicities of both therapies, and shared his views on the optimal sequencing of the two agents.

How do Stivarga and Lonsurf compare?

These are very different agents. Stivarga is an agent that is essentially more of a biological multitargeted tyrosine kinase inhibitor. It hits multiple targets; it's what we call a “dirty drug.” It has too many targets.

Lonsurf is more of a traditional chemotherapy agent. It is oral — as Stivarga is — but it is a cytotoxic agent. It has some properties that allow it to work even when patients are exposed to 5-FU (5-fluorouracil) and fail.

Is there an understanding of the optimal sequencing for the two agents?

These agents were tested in very similar settings, but they have never been compared head-to-head.

Stivarga was compared with placebo in a large study and it showed superiority to placebo in all parameters. Lonsurf was also compared with placebo and also showed an improvement in all efficacy parameters.

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