Dr. Ajani on the FDA Approvals of Nivolumab Plus Chemotherapy and Nivolumab Plus Ipilimumab in ESCC

Jaffer A. Ajani, MD, a professor in the Department of Gastrointestinal Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses how the FDA approvals of first-line nivolumab (Opdivo) plus chemotherapy and nivolumab plus ipilimumab (Yervoy) in advanced or metastatic esophageal squamous cell carcinoma (ESCC) will improve treatment in this setting.

In May 2022, the FDA approved the combination of nivolumab and fluoropyrimidine- and platinum-containing chemotherapy, as well as the combination of nivolumab and ipilimumab, as frontline therapy in adult patients with unresectable advanced or metastatic ESCC, irrespective of PD-L1 status. This approval was based on data from the phase 3 CheckMate 648 trial (NCT03143153), in which both combinations improved overall survival compared with chemotherapy alone in the all-randomized population and in patients with a PD-L1 expression of 1% or higher.

The CheckMate 648 trial measured PD-L1 expression with tumor proportion scores, where a score of 1 or higher was positive, and a score lower than 1 was negative, Ajani says. As a positive tumor proportion score translates to positive PD-L1 expression, tumor proportion score is an effective way to distinguish which patients may derive the most benefit from the combinations, Ajani explains.

Although the FDA has approved nivolumab plus chemotherapy and nivolumab plus ipilimumab for all patients with unresectable advanced or metastatic ESCC regardless of tumor proportion score, as both combinations are less effective in subsets with negative PD-L1 expression, increased discernment is recommended when considering these combinations for these patients, Ajani says. Overall, this approval will simplify the treatment paradigm for ESCC, Ajani concludes.