Study confirms regorafenib benefit for previously treated metastatic colorectal cancer

Regorafenib appeared safe and effective for patients with previously treated metastatic colorectal cancer, according to the results of the phase 3b CONSIGN study presented at the European Society for Medical Oncology’s World Congress on Gastrointestinal Cancer.

Regorafenib (Stivarga, Bayer Healthcare) — an oral multikinase inhibitor that targets tumor angiogenesis, oncogenesis and the tumor microenvironment — significantly improved survival compared with placebo in patients with previously treated metastatic colorectal cancer in the phase 3 CORRECT trial (Grothey A, et al. Lancet. 2013;doi:10.1016/S0140-6736(12)61900-X), according to study background.

Eric Van Cutsem, MD, PhD, professor of internal medicine at the University of Leuven in Belgium and an ESMO executive board member, and colleagues initiated the phase 3b CONSIGN study to confirm the findings from the CORRECT trial — which served as the basis for regorafenib’s approval — to allow patients access to the drug before marketing authorization, and to evaluate the safety of regorafenib in a large cohort.

The single-arm study included 2,864 patients (median age, 62 years) with previously treated metastatic colorectal cancer. Inclusion criteria included disease progression following standard approved therapies and an ECOG performance status of 0 to 1.

The researchers assigned patients 160 mg of regorafenib once daily for the first 3 weeks of each 4-week cycle. Treatment continued until disease progression, death or unacceptable toxicity.

Safety served as the primary endpoint. PFS served as a secondary endpoint.

Over half of the evaluable patients harbored a KRAS mutation, and 96% had received two or more prior lines of therapy. The researchers observed an average treatment length of 2.5 months (range, 0-30).

Eighty percent of patients experienced grade 3 or higher adverse events. Grade 5 adverse events occurred in 16% of patients; however, researchers deemed only 0.5% to be treatment related.

The most frequently reported adverse events included fatigue (18%), hypertension (17%), hand–foot skin reaction (14%), hypophosphatemia (7%) and diarrhea (6%).

Twenty-five percent of patients discontinued treatment due to adverse events.

Grade 3 or worse treatment-emergent laboratory toxicities that occurred in patients included bilirubin (13%), increased aspartate aminotransferase (7%), increased alanine aminotransferase (6%), anemia (4%) and thrombocytopenia (2%).

One nonfatal case of severe drug-induced liver injury occurred.

Researchers estimated a median PFS of 2.7 months (95% CI, 2.6-2.7). Patients with KRAS wild-type tumors and KRAS mutations achieved a similar median PFS (2.8 months vs. 2.5 months).

“This study in a real world population of patients with previously treated metastatic colorectal cancer shows a similar safety profile and PFS with regorafenib as shown in the randomized CONNECT trial,” Van Cutsem said in a press release. “The findings add to our knowledge of how to select patients and how to manage toxicities. We need to establish clear guidelines on the management of adverse events to make taking the drug more tolerable for patients.” – by Cameron Kelsall

Reference:

Van Cutsem E, et al. Abstract LBA-05. Presented at: ESMO 17th World Congress on Gastrointestinal Cancer; July 1-4, 2015; Barcelona.

Disclosure: Van Cutsem reports receiving research funding from Eli Lilly and Co. HemOnc Today could not verify the other researchers’ relevant financial disclosures.