Date: 2012-01-18
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the 2012 Gastrointestinal Cancers Symposium of the American Society of Clinical Oncology (ASCO-GI)
Company: Bayer Healthcare (Germany)
Product: regorafenib (BAY 73-4506)
Action
mechanism: multi-kinase inhibitor. Stivarga® (regorafenib) is an oral multi-kinase inhibitor that inhibits various kinases within the mechanisms involved in tumor growth and progression - angiogenesis, oncogenesis and the tumor microenvironment. In preclinical studies, Stivarga inhibits several angiogenic VEGF receptor tyrosine kinases that play a role in tumor neoangiogenesis (the growth of new blood vessels). In addition to VEGFR 1-3 it also inhibits various oncogenic and tumor microenvironment kinases including TIE-2, RAF-1, BRAF, BRAFV600, KIT, RET, PDGFR, and FGFR, which individually and collectively impact upon tumor growth, formation of a stromal microenvironment and disease progression.
Disease: metastatic colorectal cancer
Therapeutic area: Cancer - Oncology
Country: North America, Europe, China, Japan and Australia.
Trial
details: The CORRECT trial is an international, multicenter, randomized, double-blind, placebo-controlled study that enrolled 760 patients with mCRC whose disease has progressed after approved standard therapies. Patients were randomized to receive either regorafenib plus best supportive care (BSC) or placebo plus BSC. Treatment cycles consisted of 160 mg of regorafenib (or matching placebo) once daily for three weeks on / one week off plus BSC. The primary endpoint of this trial was overall survival. Secondary endpoints included progression-free survival, objective tumor response rate and disease control rate. The safety and tolerability of the two treatment groups were also compared.
Latest
news: * On January 18, 2012, Bayer HealthCare has announced that data on regorafenib from the Phase III CORRECT (Colorectal cancer treated with regorafenib or placebo after failure of standard therapy) trial will be presented as a late breaking abstract in an oral abstract session at the 2012 Gastrointestinal Cancers Symposium of the American Society of Clinical Oncology (ASCO-GI). The study met its primary endpoint of significantly improving overall survival (OS) by 29% (HR=0.77, p=0.0052). The CORRECT trial also met two secondary efficacy endpoints, including a significant improvement in progression-free survival (PFS) (HR=0.49, p<0.000001), and a significant improvement in the disease control rate (DCR) (p<0.000001). The difference in the objective response rate (ORR) between the two arms did not reach statistical significance. * On October 26, 2011, Bayer HealthCare has announced positive results from its Phase III trial evaluating its investigational compound regorafenib for the treatment of patients with metastatic colorectal cancer (mCRC) whose disease has progressed after approved standard therapies.
The efficacy analyses showed that patients who were treated with regorafenib had the following outcomes:
• A median OS of 6.4 months compared to 5.0 months for the placebo group (HR=0.77, p=0.0052)
• A median PFS of 1.9 months compared to 1.7 months for the placebo group (HR= 0.49, p<0.000001)
• A DCR of 44.8% compared to 15.3% for the placebo group (p<0.000001)
• An ORR of 1.0% compared to 0.4% for the placebo group (p=0.188)
The overall safety and tolerability profile for regorafenib was consistent with results from previous studies. The most common drug-related, treatment-emergent adverse events (occurring in at least 25% of patients) included fatigue (47.4% vs. 28.1%), hand-foot skin reaction (46.6% vs. 7.5%), diarrhea (33.8% vs. 8.3%), anorexia (30.4% vs. 15.4%), voice changes (29.4% vs. 5.5%), hypertension (27.8% vs. 5.9%), oral mucositis (27.2% vs. 3.6%), and rash/desquamation (26.0% vs. 4.0%) for patients receiving regorafenib as compared to placebo.
The CORRECT trial was unblinded in late 2011 following a pre-planned interim analysis that determined that the regorafenib arm showed significant improvement in overall survival, and patients on the placebo arm were offered treatment with regorafenib.
Bayer plans to submit regorafenib for marketing authorization in mCRC in 2012.The trial met its primary endpoint of statistically significantly improving overall survival. This is the result of a pre-planned interim analysis conducted by an independent Data Monitoring Committee (DMC) of the CORRECT (Patients with metastatic colorectal cancer treated with regorafenib or placebo after failure of standard therapy) trial. Per the recommendation of the DMC, the study has been unblinded and patients in the placebo arm will be offered treatment with regorafenib. In this trial, the safety and tolerability of regorafenib were generally as expected and did not show any new or unexpected toxicities. Data from the study are expected to be presented at a forthcoming scientific meeting.
Bayer will continue discussions with health authorities worldwide, including the EMA and the FDA regarding next steps in filing for approval of regorafenib in the treatment of mCRC.
