FDA Approves 2 Opdivo-Based Regimens for Esophageal Squamous Cell Carcinoma

The Food and Drug Administration (FDA) approved two immunotherapy-based treatments for patients with esophageal squamous cell carcinoma, regardless of PD-L1 status: Opdivo (nivolumab) plus fluoropyrimidine- and platinum-containing chemotherapy, as well as Opdivo plus Yervoy (ipilimumab).

“Today’s approvals bring two first-line immunotherapy-based treatment options at once, Opdivo in combination with chemotherapy and Opdivo plus Yervoy as the first dual immunotherapy option, to newly diagnosed patients with unresectable advanced or metastatic esophageal squamous cell carcinoma, further building on the role of Opdivo-based regimens in upper gastroesophageal cancers,” Adam Lenkowsky, senior vice president and general manager, U.S. Cardiovascular, Immunology, Oncology at Bristol Myers Squibb, the manufacturer of Opdivo and Yervoy, said in a press release.

The approval is based off findings from the phase 3 CheckMate-648 clinical trial, the largest phase 3 trial of an immunotherapy in frontline immunotherapy for this patient population. The trial evaluated Opdivo and chemotherapy in 321 patients and Opdivo plus Yervoy in 325. Then each group was compared to chemotherapy alone in 324 patients.

Findings showed that both Opdivo-based treatment combinations led to improved overall survival (time from treatment to death of any cause) compared to chemotherapy alone. In patients who received Opdivo in combination with chemotherapy, average overall survival was 13.2 months, whereas it was 10.7 months in the chemotherapy groups.

In patients whose tumors expressed PD-L1 (the molecule that Opdivo targets) at or greater than 1%, average overall survival was 15.4 months for Opdivo plus chemotherapy, compared to 9.1 months in chemotherapy alone.

Average overall survival among the whole study group was 12.8 months for those who were prescribed Opdivo and Yervoy and 10.7 months for those prescribed chemotherapy alone. For patients whose tumors were PD-L1—positive, Opdivo plus Yervoy led to a 13.7-month average progression-free survival (time from treatment until disease worsens) and 9.1-month average progression-free survival in those who received chemotherapy alone.

Average progression-free survival was 5.8 months for patients who received Opdivo plus chemotherapy, compared to 5.6 months for those who received chemotherapy alone, though the difference between the groups was not statistically significant. However, there was a statistically significant improvement in progression-free survival for patients whose tumors expressed PD-L1, with an average of 6.9 months and 4.4 months in the Opdivo-containing and chemotherapy groups, respectively.

Progression-free survival for patients whose tumors were PD-L1—positive was four months for the Opdivo plus Yervoy group, compared to 4.4 months in the chemotherapy alone group which, again, was not statistically significant.

Opdivo and Yervoy can come with severe — or even fatal — immune-related side effects, such as pneumonitis, colitis, hepatitis, liver damage, endocrinopathies, nephritis, kidney damage and skin side effects. The drugs also carry risk of other side effects, including infusion reactions, complications with hematopoietic stem cell transplant and embryo-fetal toxicity.

“Today brings welcome news for many advanced or metastatic esophageal squamous cell carcinoma patients and oncologists,” Dr. Jaffer A. Ajani, CheckMate -648 co-first author and lead U.S. investigator, and professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, said in the release. “Unresectable advanced or metastatic esophageal squamous cell carcinoma is a challenging disease, and there’s a need for additional treatment options that may extend survival in the first-line setting.In the CheckMate -648 trial, two (Opdivo)-based combinations showed a survival benefit compared to chemotherapy alone, offering new treatment options regardless of PD-L1 status.”

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