Immunotherapy Shows Promise Against Previously Untreatable Stomach Cancer

Stomach cancer patients who no longer respond to treatment may soon have a new option available to them that mobilizes their own immune system to combat cancer.

On Thursday, Bristol-Myers Squibb (BMS) revealed the results from their ONO-4538-12 clinical trial and showed that the checkpoint inhibitor nivolumab (Opdivo ®) benefited patients with advanced stomach cancer who could not be helped by surgery or chemotherapy. Compared to the control group, nivolumab treatment was associated with a 37% decrease in risk of death, and 26.6% of patients who received it survived for at least one year, compared to just 10.9% of those who did not.

Nivolumab works by blocking the PD-1/PD-L1 pathway and preventing anti-cancer T cells from being de-activated by the tumor. While nivolumab and other checkpoint inhibitors have proven effective against several cancers, this was “the first randomized, phase III immuno-oncology trial to demonstrate improved survival for patients with previously treated advanced or recurrent gastric cancer,” according to Ian M. Waxman, MD, the development lead for Gastrointestinal Oncology at BMS.

Nivolumab as a single agent is not the only immunotherapy currently being investigated for its ability to help them. One phase III trial is investigating the combination of nivolumab and ipilimumab (Yervoy ®), an anti-CTLA-4 checkpoint inhibitor, while others are investigating pembrolizumab (Keytruda ®) and avelumab, both of which are checkpoint inhibitors that target PD-1 and PD-L1, respectively. It’s also worth noting that two of these trials―one with pembrolizumab and the other with avelumab―are evaluating the effectiveness of these immunotherapies as first-line therapies for previously untreated patients with advanced stomach cancer.

Beyond checkpoint inhibitors, another phase III trial is combining two anti-HER-2 antibody immunotherapies, one of which, trastuzumab (Herceptin ®) is already available in combination with chemotherapy for patients with tumors that overexpress HER-2. Others, including CAR T cells (NCT02617134 and NCT02349724) and vaccines (NCT02317471 and NCT01376505), are in earlier stage trials.

The diversity of these immunotherapy efforts offer great potential for the future and should provide great hope for stomach cancer patients. As Geoffrey Ku, MD, a medical oncologist with Memorial Sloan Kettering Cancer Center notes, “to the degree that immunotherapy has transformed the treatment of many other cancers, it is on the verge of transforming esophageal and stomach cancer.”

Stomach cancer claims the lives of more than 10,000 people each year in the United States. When detected early, it is usually treatable with traditional therapies. However, once it has metastasized, or spread, to distant organs, the five-year survival rate plummets to only four percent. Clearly, patients with advances cases need better treatment options. With this latest announcement from BMS and the ongoing work of other companies and institutions, the outlook is promising.