FDA Approves Opdivo for Advanced Esophageal Cancer

FDA Approves Opdivo for Advanced Esophageal Cancer

The U.S. Food and Drug Administration (FDA) has approved Opdivo (nivolumab) for the treatment of people with advanced, inoperable, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) previously treated with fluoropyrimidine– and platinum-based chemotherapy.

The approval came after the regulatory agency granted priority review to the application. It was based on data from the ATTRACTION-3 Phase 3 clinical trial (NCT02569242), which showed that Opdivo significantly extends survival compared with standard chemo.

With this approval, Bristol Myers Squibb‘s Opdivo has now become the first immunotherapy to be approved for patients with advanced ESCC, regardless of PD-L1 levels in their cancer cells.

“Many cases of esophageal cancer are diagnosed at the advanced stage, when the disease could have a significant impact on a patient’s health. Treatment options can be limited once patients with advanced esophageal squamous cell carcinoma progress,” Adam Lenkowsky, general manager and head of U.S. Oncology, Immunology, Cardiovascular at Bristol Myers Squibb, said in a press release.

“The approval of Opdivo as a new treatment option for previously treated patients with advanced esophageal squamous cell carcinoma, regardless of PD-L1 expression, highlights our commitment to providing new options to address the unmet needs of patients and brings us another step closer to understanding the full potential of immunotherapy for gastrointestinal cancers,” Lenkowsky said.

Opdivo belongs to a class of medications called immune checkpoint inhibitors that block the activity of proteins cancer cells use to avoid being targeted and destroyed by immune cells.

In the case of Opdivo, it blocks the activity of a protein receptor found on the surface of immune cells, called PD-1, preventing it from interacting with its ligands, PD-L1 and PD-L2. This allows immune cells to recognize and eliminate cancer cells more effectively.

ATTRACTION-3 compared the safety and efficacy of Opdivo to that of conventional chemotherapy in patients with advanced ESCC that could not be removed surgically and who were either resistant or intolerant to fluoropyrimidine- and platinum-based therapies.

The study enrolled 419 patients who were assigned randomly to receive either Opdivo or standard chemotherapy with docetaxel or paclitaxel, all given intravenously until disease progression or unacceptable toxicity.

Findings from ATTRACTION-3 showed that those receiving Opdivo lived longer than those treated with standard chemotherapy (10.9 versus 8.4 months), demonstrating that Opdivo reduced the risk of death by 23%.

This survival benefit was observed in all patients treated with Opdivo, regardless of levels of PD-L1 in their tumors. (PD-1 checkpoint inhibitors like Opdivo tend to work better when cancer cells produce high levels of the ligand PD-L1.)

Although no statistically significant differences were observed in the number of patients responding to treatment in both groups — 19.3% for Opdivo vs. 21.5% for chemo — those who received Opdivo had longer responses compared to those given standard chemotherapy (6.9 months vs. 3.9 months).

Patients on Opdivo tended to live less time without disease progression (1.7 months), compared with 3.4 months for chemo, but this measure was not tested for statistical significance.

Serious adverse side effects were observed in approximately a third (38%) of the patients who received the therapy during ATTRACTION-3. The most common serious side effects reported included fever, pneumonia, interstitial lung disease (ILD), and esophageal fistula (abnormal connection between the esophagus and trachea).

In addition to ESCC, Opdivo has been approved by the FDA for treating lymphoma and multiple types of solid cancers, including melanoma, bladder, colorectal, head and neck, kidney, liver, and lung cancer.