Opdivo and Stivarga Plus Chemotherapy Improves Outcomes in Certain Gastric Cancers

Opdivo (nivolumab) combined with Stivarga (regorafenib) and chemotherapy as first-line treatment has been shown to improve the time a patient lives before death or disease worsening in patients with advanced esophageal adenocarcinoma, a type of esophagus cancer, according to recent research published in The Lancet Oncology.

According to Memorial Sloan Kettering Cancer Center (MSKCC) in New York City, where the study was performed, esophageal adenocarcinoma is considered the most common type of esophageal cancer in the United States, constituting more than half of all new cases. Specifically, this type of cancer starts out in the glandular cells, which are not present in the esophagus lining, according to MSKCC. It also established that adenocarcinoma mainly occurs at the lower end of the esophagus and the upper section of the stomach.

Opdivo is a type of drug known as an immune checkpoint inhibitor, that binds to the protein, PD-1, and blocks this protein, which helps the immune system effectively kill cancer cells, as defined by National Cancer Institute. Opdivo was approved by the Food and Drug Administration (FDA) in April 2021 in combination with chemotherapy to treat patients with stomach cancer.

Stivarga is a type of kinase (a type of enzyme) inhibitor that blocks certain proteins, which can ultimately prevent cancer cells from growing, according to National Cancer Institute. The organization also determined that the drug prevents the growth of new blood vessels that tumors need in order to grow.

In the study, there was a total of 35 patients with advanced esophageal, gastric or gastroesophageal junction adenocarcinoma, who had not been previously treated, with a median follow-up of 18.1 months.

"Regorafenib's ability to disrupt the tumor’s immunosuppressive environment can lead to more robust anti-tumor immune response when triggered by nivolumab.”

— Dr. Yelena Janjigian

The treatment combination of Opdivo and Stivarga plus chemotherapy offered benefits to patients with these types of cancers, as “(Stivarga’s) ability to disrupt the tumor’s immunosuppressive environment can lead to more robust anti-tumor immune response when triggered by (Opdivo),” Dr. Yelena Janjigian, chief of gastrointestinal oncology service at MSKCC and Dr. Sam Cytryn, senior medical oncology fellow at MSKCC, both co-authors of the respective study, said during an email interview with CURE®.

Prior to the treatment combination of Opdivo and Stivarga plus chemotherapy for patients with untreated, metastatic HER2-negative esophagogastric adenocarcinoma, a treatment option was Opdivo with chemotherapy as first-line treatment (initial treatment for patients). However, Janjigian and Cytryn noted that adding Stivarga to the current treatment combination “may be able to shrink the tumor more effectively, extend the time before the tumor develops resistance to treatment and ultimately extend a patient’s life beyond what nivolumab and chemotherapy can do without regorafenib.”

The study’s primary endpoint (the main result that measures a treatment’s efficacy) was progression-free survival (the period during and after treatment of cancer when the disease does not worsen) was met, researchers reported.

“In our study, in which all patients received regorafenib with nivolumab and chemotherapy, 71% were alive and had not developed progression of their disease after six months on treatment,” said Janjigian and Cytryn. “This compared favorably to what has historically been reported for nivolumab and chemotherapy without regorafenib, in which only 53% of patients were alive and progression-free at six months.

“Additionally, in our study, half of all patients were alive and progression-free after 13 months, which also compares favorably to the historical control in which half of patients were alive and progression-free after approximately eight months, with nivolumab and chemotherapy without regorafenib.”

Janjigian and Cytryn also discussed the treatment combination’s side effects.

Half the patients in the study were alive and without disease progression at 13 months, explained Dr. Sam Cytryn.

“The most common side effects we observed were fatigue and sensory neuropathy (pain, numbness or weakness in the hands and feet),” Janjigian and Cytryn said. “The most common severe side effect we observed was a decrease in neutrophils (a type of white blood cell) responsible for fighting infection. However, only 18% of patients had to stop regorafenib and only 13% of patients had to stop nivolumab because of side effects.”

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