Study confirms benefits of regorafenib in Asians with colorectal cancer

Last Updated: 2015-06-05

By Larry Hand

NEW YORK (Reuters Health) - A second phase 3 clinical trial has shown overall survival benefit for regorafenib compared with placebo in patients with refractory metastatic colorectal cancer, this time with an all-Asian study population.

Dr. Tae Won Kim, of the Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea, and colleagues recruited adult patients from 25 hospitals in China, Hong Kong, South Korea, and Vietnam for the trial, called CONCUR. Each patient had confirmed adenocarcinoma of the colon or rectum, and metastatic disease and disease progression, but with a life expectancy of at least three months.

Eligible patients (n=204) had to have received at least two previous treatment lines, including fluoropyrimidine plus oxaliplatin or irinotecan. They also could, but were not required to, have previous treatment with bevacizumab, cetuximab, or panitumumab.

The researchers randomized the patients 2:1 to receive regorafenib (Stivarga, Bayer HealthCare) 160 mg or placebo orally once daily on days 1-21 of each 28-day cycle, and patients and investigators were masked to treatment. All patients received best supportive care. Investigators followed up on patients every two weeks for the first six cycles, then monthly.

The researchers found that overall survival, the primary endpoint, was significantly better in the regorafenib group (hazard ratio, 0.55; p=0.00016).

Median overall survival came to 8.8 months for the regorafenib group, compared with 6.3 months for the placebo group, the researchers reported online May 13 in the Lancet Oncology.

They found progression-free survival was also better in the regorafenib group (3.2 months vs. 1.7 months).

Drug-related grade 3 or worse adverse events occurred in 54% of patients in the regorafenib group and 15% of patients in the placebo group. The most frequent events were hand-foot skin reaction and hypertension. As of analysis cut-off date, 70% of the patients on regorafenib and 88% of those on placebo had died.

In a subgroup analysis comparing patients who had and had not received previous targeted biological treatment, the hazard ratio for overall survival was 0.31 in favor of regorafenib in patients who had not and to 0.78 in patients who had received at least one targeted biological drug.

In the previous trial, called CORRECT (http://bit.ly/1Qpv7fM), all patients had received a targeted biological drug. The hazard ratio in that trial was similar to the one for CONCUR patients who had received a biological drug.

Also in the CORRECT trial, of the larger study population (n=760), only 15% were Asians, mostly Japanese.

"The studies are different in their size (CORRECT was much larger) and different in the geographic location where the studies were conducted, and they're different in the patient population in terms of how heavily they were pretreated," Dr. Alex Grothey, of the Mayo Clinic in Rochester, Minnesota, who co-authored an accompanying editorial, told Reuters Health. "Any of those points could explain why the results are stronger than what we saw in CORRECT."

"The CONCUR study, I think, is, because of the data that we've known before, kind of another added data point saying that the CORRECT study was really on the mark," he said.

Dr. Grothey, also an investigator in the CORRECT trial, which formed the basis for the Food and Drug Administration approval of regorafenib for treatment-refractory disease, said the CONCUR results point more toward the pretreatment population than just-Asian patients in terms of overall survival benefit.

"One of the hypotheses is if you have less heavily pretreated patients you might have a larger benefit," he said. But the trial's small size would not justify a change in indication for the drug, he added.

"It can inform clinical practice, even with the label the FDA has approved now," he said. "Patients might start with a first-line treatment option, go to second line, third line, then they might go back to the first-line treatment option after some time. But it could very well be that before you recycle the old treatment, patients go to other options."

Another option that may be in line for future approval, Dr. Grothey added, is TAS-102, which he called "this new drug that we all are waiting for to get approved."

Bayer HealthCare -- which funded the research, employed two of the authors and supported three others -- issued a statement in response to the new results:

"While the CONCUR study was similar in design to the CORRECT trial, it was conducted in a broader Asian population with the purpose of supporting registration in China and other Asian countries; the registrational trial for U.S., Europe, and other countries was the CORRECT trial. CONCUR . . . further supports the safety and efficacy of Stivarga in patients with (metastatic colorectal cancer). Bayer is working with health authorities worldwide to update the product information where applicable. In the U.S., no indication change is planned based on these data."

Dr. Kim did not respond to a request for comments by deadline.

SOURCE: http://bit.ly/1BclFFx and http://bit.ly/1FBlmvc

Lancet Oncol 2015.