On July 30, 2014 Bayer reported that the oncology compound Stivarga (regorafenib) has been approved by the European Commission (EC) for the treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumors (GIST) who progressed on or are intolerant to prior treatment with imatinib and sunitinib (Press release Bayer, JUL 30, 2014, View Source [SID:1234500668]). The approval of Stivarga in GIST is based on results from the pivotal Phase III study (GRID) that demonstrated a statistically significant improvement in progression-free survival (PFS) compared to placebo in patients with GIST whose disease had progressed after prior treatments. Stivarga is already approved in the EU for the treatment of patients with metastatic colorectal cancer (mCRC).

“Following the approval of Stivarga for GIST in several countries worldwide, including the U.S. and Japan, we are delighted to offer patients in Europe a new option for treating this rare yet relentless cancer,” said Dr. Joerg Moeller, Member of the Bayer HealthCare Executive Committee and Head of Global Development. “At Bayer, we are dedicated to exploring solutions for different tumor types and drive innovation to meet the unmet needs of both physicians and patients.”

“GIST is a highly aggressive cancer that can go undetected for years and, at the point of diagnosis, most patients have already progressed to advanced stages of disease. Survival rates are low and treatments are limited after imatinib and sunitinib,” said Jean Yves-Blay, GRID investigator, Professor of Medicine in Medical Oncology and Head of the Medical Oncology Department, Centre Leon Berard at Université Claude Bernard in Lyon, France. “The Phase III GRID trial demonstrated that progression-free survival with regorafenib is more than five times than with placebo, a significant improvement for those who have progressive disease.”

“One of the hardest things to hear from your doctor is that there is no treatment left for your disease,” said Markus Wartenberg, Member of the Board of Directors of the Sarcoma Patients EuroNet Association (SPAEN). “In rare cancers such as GIST, hope empowers people to continue fighting the cancer. New treatment options are welcomed so that patients can continue to defy their illness.”

The results of the pivotal Phase III GRID study showed that regorafenib plus best supportive care (BSC) significantly improved progression-free survival (PFS) compared to placebo plus BSC (HR=0.268 [95% CI 0.185-0.388], p<0.0001) in patients with metastatic and/or unresectable GIST who were previously treated with imatinib and sunitinib, reducing the risk of progression or death by 73%. The median PFS was 4.8 months in the regorafenib arm versus 0.9 months in the placebo arm (p<0.0001). The increase in PFS was consistent and independent of patient age, sex, geographic region, prior lines of treatment or ECOG performance status. In clinical trials, the most frequently reported drug-related adverse events in regorafenib-treated patients versus placebo-treated patients, respectively, were: asthenia/fatigue, hand-foot skin reaction (HFSR) / palmar-plantar erythrodysesthesia (PPE), diarrhea, decreased appetite and food intake, hypertension, mucositis, dysphonia, infection, pain (not otherwise specified), decreased weight, gastrointestinal and abdominal pain, rash, fever and nausea. The most serious adverse drug reactions in patients receiving regorafenib are hepatotoxicity, hemorrhage, and gastrointestinal perforation. Adverse events in regorafenib-treated patients generally occur early (within the first two treatment cycles), therefore it is advised to monitor patients closely. Full results from the GRID study were presented at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in June 2012 and published in November 2012 in The Lancet. Regorafenib has been approved under the brand name Stivarga in several countries, including the U.S. and Japan, for the treatment of GIST. In 60 countries worldwide, including the U.S., Europe and Japan, the product has also been approved for the treatment of patients with metastatic colorectal cancer (mCRC). About the GRID Study GRID (GIST – Regorafenib In Progressive Disease) was a randomized, double-blind, placebo-controlled, multi-center Phase III study of regorafenib for the treatment of GIST. It randomized 199 patients whose disease had progressed despite prior treatment with imatinib and sunitinib. Patients were randomized in a 2:1 ratio to receive either regorafenib plus BSC or placebo plus BSC to evaluate efficacy and safety. Treatment cycles consisted of 160 mg regorafenib (or matching placebo) once daily for three weeks on / one week off plus BSC. The primary endpoint was PFS, and secondary endpoints included OS, time to progression, disease control rate, tumor response rate, and duration of response. The safety and tolerability of the two treatment groups were also compared. Patients initially randomized to placebo were allowed to cross over to open-label regorafenib once the disease progressed.