The latest results on Bayer HealthCare’s investigational compound regorafenib (BAY 73-4506) from the international, multicenter, randomized, double-blind, placebo-controlled Phase III CORRECT (Colorectal cancer treated with regorafenib or place after failure of standard therapy) trial have been announced by Bayer HealthCare.
The study, conducted in North America, Europe, Australia, Japan and China enrolled 760 individuals with metastatic colorectal cancer (mCRC), whose disease had progressed during or within 3 months following last administration of approved standard therapies, such as oxaliplatin, bevacizumab and cetuximab, irinotecan, fluropyrimidine, and pantiumumab.
Participants were randomized to two groups. One group received regorafenib in addition to best supportive care (BSC), while the other group received placebo in addition to BSC. Participants received 160 mg of regorafenib (or 160 mg placebo) once a day for three weeks, on one week off the next, in addition to BSC.
Individuals who discontinued standard treatment because of unacceptable toxicity and precluding pretreatment, with the same agent before disease progression, were permitted to participate in the investigation.
The Phase III CORRECT study met its primary endpoint, showing statistically considerable improvement in overall survival (OS) by 29% (HR=0.77, p=0.0052). Median OS for regorafenib plus BSC participants was 6.4 months, compared with 5.0 months for those who received placebo plus BSC.
Secondary endpoints of the study showed statistically considerable improvement in progression-free survival (PFS) (HR=0.49, p<0.000001), median PFS was 1.9 months for the regorafenib group, compared to 1.7 months for the placebo group, as well as improvement in disease control rate (44.8% vs. 15.3%, respectively). Between the regorafenib group and placebo group, the difference in objective response rate did not reach statistical significance (1.0% vs. 0.4%).
The most prevalent drug-associated, treatment-emergent side effects between the participants receiving regorafenib compared to placebo included:
*diarrhea – 33.8% vs. 8.3%
*fatigue – 47.4% vs. 28.1%
*anorexia – 30.4% vs. 15.4%
*hand-foot skin reaction – 46.6% vs. 7.5%
*oral mucositis – 27.2% vs. 3.6%
*rash/desquamation – 26.0% vs. 4.0%
*hypertension – 27.8% vs. 5.9%
In late 2011, the CORRECT study was unblinded after the recommendation from an independent Data Monitoring Committee. As results from the study showed that overall survival in participants receiving regorafenib considerably improved, those on placebo were offered treatment with regorafenib.
This year, Bayer HealthCare plans to submit the drug for marketing authorization in mCRC.
Axel Grothey, M.D., Professor of Oncology, Mayo Clinic and co-principal investigator of the CORRECT study, will present the updated data in an oral abstract session (LBA No. 385, January 21, 2012 from 2:30 p.m. – 4:00 p.m. PT, Level 3 Ballroom, Moscone Center West) at the 2012 Gastrointestinal Cancers Symposium of the American Society of Clinical Oncology (ASCO-GI), in San Francisco, CA.
Regorafeniv is an investigational oral multi-kinase inhibitor targeting angiogenic, stromal and oncogenic kinases. At present, the drug is being tested in human trials for its potential to treat individuals with different tumor types.
Regorafenis is not approved by the EMA, FDA or other health authorities.
About Colorectal Cancer
Colorectal cancer, commonly known as bowel cancer, is a cancer from uncontrolled, malignant cell growth in the colon and rectum. Most cancers in the colon and rectum are adenocarcinomas, which are responsible for over 90% of all large bowel tumors.
In the U.S., colorectal cancer is the third most prevalently diagnosed cancer, and the third leading cause of cancer death in both men and women. In 2011, it was estimated that over 140,000 individuals will be diagnosed with the disease, and almost 50,000 will die from it. Around 50% of individuals with colon cancer will be diagnosed with metastases (most commonly to the liver) either at the time of diagnosis, or as a result of recurrent disease.