On Friday, September 22, 2017, the FDA approved anti-PD-1 checkpoint immunotherapies for two additional cancer types. Now, patients with the most common form of liver cancer who have been previously treated with sorafenib can receive nivolumab (Opdivo®, Bristol-Myers Squibb), while patients with advanced, recurrent stomach or gastroesophageal cancer that expresses PD-L1 can receive pembrolizumab (Keytruda®, Merck).
While both immunotherapies have already been approved for other cancer types, these mark the first checkpoint immunotherapy approvals for liver, stomach, and gastroesophageal cancer, and the first approval of any immunotherapy for liver cancer. Two antibody-based immunotherapies—the anti-HER2 trastuzumab (Herceptin®, Genentech) and anti-VEGFR2 ramucirumab (Cyramza®, Eli Lilly)—are already approved for stomach and gastroesophageal cancer.
Nivolumab’s approval was based on the phase I/II CheckMate-040 clinical trial in which 154 patients with hepatocellular carcinoma (or HCC, a type of liver cancer) were treated. Under the HCC-modified RECIST criteria, nearly one in five patients (18.2%) experienced either a partial or complete response. Several of these responses, which took place 2.8 months after treatment on average, have also been durable. More than half these responses lasted more than a year, and one patient has experienced more than three years with no evidence of disease. With respect to safety, 11% of patients had to discontinue treatment due to side effects, while 32% had to have a dose delayed.
Pembrolizumab’s approval was based on the phase II Keynote-059 clinical trial in which 259 patients with stomach or gastroesophageal cancer were treated. Of these 259 patients, 143 (55%) had tumors that were defined as PD-L1-positive (characterized by a combined positive score, or CPS, ≥1). PD-L1 expression, by both tumor cells and immune cells in the tumor environment, is significant because by binding and activating the PD-1 receptor, PD-L1 signaling can shut down cancer-fighting T cells and prevent them from eliminating tumors. Of these patients with PD-L1-expressing tumors, 13.3% experienced partial or complete responses, and 26% of these responses lasted more than a year.
To build upon the progress that these approvals represent, the Cancer Research Institute (CRI) remains committed to funding projects that might provide further help for patients with these types of cancers. With respect to liver cancer, CRI scientists are exploring several immune-related avenues that could yield clinical benefits, including: reverse engineering antibodies against the hepatitis C virus, a major cause of liver cancer (Andrew I. Flyak, Ph.D.); the role that immune cells called macrophages play in tumor development and survival (Zihou Deng, Ph.D.); and how obesity can influence liver homeostasis and create an inflammatory environment that promotes the development of liver disease and cancer (Chaoran Li, Ph.D., and Zhenyu Zhong, Ph.D.).
CRI also recently partnered with the Fibrolamellar Cancer Foundation to fund four researchers investigating how immunotherapy might enable improved outcomes for the predominantly pediatric patients with this rare type of liver cancer (fibrolamellar hepatocellular carcinoma, or FL-HCC).
With respect to esophageal cancer, Monica Olcina, Ph.D., of the Stanford University School of Medicine, is determining how different doses of radiation therapy influence immune responses against tumors in order to figure out how it could most effectively be combined with immunotherapy to maximize potential patient benefits.