The immune checkpoint inhibitor nivolumab may be a safe and effective treatment for people with advanced gastric or esophagogastric junction cancer who failed standard chemotherapy regimens, results from a Phase 3 clinical trial suggest.

A three-year survival analysis of the trial, called ATTRACTION-2 (NCT02267343), showed that the treatment significantly extended patients’ lives and the time they lived without disease worsening compared to those taking a placebo.

Findings were described in the poster, “A phase III study of nivolumab (Nivo) in previously treated advanced gastric or gastric esophageal junction (G/GEJ) cancer (ATTRACTION-2): Three-year update data,” and presented at the 2020 Gastrointestinal Cancers Symposium held in San Francisco, California, Jan. 23–25. This meeting is an annual initiative of the American Society of Clinical Oncology (ASCO).

Opdivo, developed by Bristol-Myers Squibb, is an antibody that prevents the PD-L1 protein on cancer cells from binding to its receptor (PD-1) on immune T-cells, an interaction that stops the immune system from recognizing the cancer as a threat.

This immunotherapy is approved for several cancer types, including melanoma, lung cancer, liver cancer, and lymphoma, among others. It was the first of its class to show benefits in people with stomach cancer who have failed or are intolerant to standard chemotherapies.

However, there is no long-term data demonstrating that effectiveness is durable among these patients.

The multicenter, double-blind, randomized ATTRACTION-2 trial was designed to evaluate the safety and effectiveness of long-term treatment with Opdivo versus a placebo in stomach cancer patients (including those with esophagogastric junction cancer) who had failed at least two prior chemotherapy regimens.

It included 493 patients at clinical sites in Japan, South Korea, and Taiwan, who were assigned randomly to Opdivo (330 patients) or a placebo (163 patients), given as into-the-vein injections every two weeks. Treatment was continued until disease progression, unacceptable adverse side effects, or withdrawal from the study.

The study’s main goal was to determine if Opdivo extended the lives of these patients compared to a placebo. Secondary measures included the time to disease progression or death (progression-free survival), objective response rate, duration of response, and safety.

An interim analysis conducted at a median follow-up of 8.9 months showed that 11.2% of patients receiving Opdivo attained a partial response to treatment, compared to none in the placebo group. Patients took a median of 1.6 months to respond and responses lasted a median of 9.5 months.

Stable disease was observed in 29.1% of Opdivo-treated patients and in 25.2% of patients on a placebo.

At the time of the analysis, survival outcomes were significantly longer with Opdivo. Overall survival was extended from a median of 4.1 months to 5.3 months, while progression-free survival rose from 1.5 to 1.6 months. This corresponded to a 37% reduction in the risk of death, and a 40% reduction in the risk of disease progression or death.

Now, a three-year analysis of the trial show that Opdivo has durable survival benefits in stomach cancer patients, maintaining the risk of death 38% lower and the risk of disease worsening or death 40% lower than a placebo.

The analysis was conducted after all patients had been followed for at least three years. Results revealed that 5.6% of patients on Opdivo were alive three years after beginning treatment, compared to 1.2% of the placebo sample.

After the same three-year period, the proportion of patients alive and progression-free was 2.4% in the Opdivo group and 0% of the placebo group.

Overall survival was particularly better for patients who had responded to Opdivo, 35.5% of whom reached the three-year mark alive. These patients lived a median of 26.7 months, well beyond the 4.1 months seen in the placebo arm.

Treatment-related side effects were similar to those observed two years after therapy was begun, with the most common being interstitial lung disease, lung and colon inflammation, rash, overactive thyroid (hyperthyroidism), and acute hepatitis.

Scientists now are looking at the patients’ clinical profiles at the beginning of the trial (meaning before treatment began) to assess if there is any factor associated with Opdivo-mediated long-term survival.

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