Bayer's Stivarga – doomed to be an also-ran?
This article was originally published in Scrip
Bayer HealthCare has halted a Phase III study of its oral multi-kinase inhibitor Stivarga (regorafenib) investigating its use as an adjuvant in patients with colorectal cancer who have undergone resection of liver metastases because it cannot get enough patients to enrol.
The COAST trial, which according to the clinicaltrials.gov database began in December 2013, has recruited just 25 patients out of a planned 750. As a result of the slow accrual rate, no study endpoints can be assessed, Bayer said, adding that there were no new safety signals.
"We are disappointed that the extensive measures to increase recruitment did not have the desired outcome…" said Dr Joerg Moeller, of the Bayer HealthCare Executive Committee and Head of Global Development. He said that the decision did not affect Bayer's commitment to Stivarga in the approved as well as potential additional indications. "We will continue to evaluate regorafenib in a number of tumor types with significant unmet medical needs, including colorectal cancer."
Stivarga was first launched in the US (where it is jointly promoted by Amgen) in September 2012 and is approved for use in metastatic colorectal cancer (mCRC) in around 70 markets. It has been additionally approved for use in gastrointestinal stromal tumors (GIST) in more than 50 countries, including the US, Europe and Japan. Sales of the product in 2014 amounted to €224m, up by 16.6% on 2013.
Stivarga was the first tyrosine kinase inhibitor (TKI) to be approved for use in colorectal cancer patients who have progressed following all other available therapies, a setting with little competition. However, it is stymied by the fact that this is a limited patient population and it also has a black box warning for hepatotoxicity. This problem, combined with the fact that there are plenty of other VEGF-targeting products on the market and in development, may explain doctors' and patients' reticence in signing up for COAST.
Even so, the product would probably have struggled to gain market share in the more lucrative earlier-line treatment of colorectal cancer without showing superiority over current therapies.
The product is also in Phase III for liver cancer and has been tested at earlier stages in other solid tumors including kidney cancer. In 2013, Bayer and Amgen announced the start of a Phase III trial in second-line treatment of hepatocellular carcinoma, in patients who have experienced disease progression after first-line therapy with Bayer/Amgen's Nexavar (sorafenib). However, here it could also be hampered by its liver toxicity black box warning, and competition from other pipeline drugs targeting the second-line setting such as Lilly's Cyramza (ramucirumab), Daiichi Sankyo's tivantinib and Bristol-Myers Squibb's Cometriq (cabozantinib).