Adjuvant Nivolumab in Esophageal or Gastroesophageal Junction Cancer: the Improvement in Progression-Free Survival Is Small

Esophageal cancer is the seventh most common cancer globally, accounting more than a half million deaths per year. Despite several therapeutic options in neoadjuvant setting, including chemoradiotherapy and surgery, no adjuvant treatment has been established for patients at high risk of recurrence. Even so, findings from the recently published CheckMate 577 trial seem to suggest an important clinical impact, in terms of disease-free progression, for the use of adjuvant nivolumab, a PDL-1 inhibitor, in resected esophageal cancer or gastroesophageal junction cancer. The authors reported a benefit for the treatment arm of 22.4 months compared with 11.0 in the placebo group. Although median is commonly used as an endpoint in survival studies, it can be influenced by the timing of a few events in the descending portion of the Kaplan–Meier curve. Restricted mean survival time (RMST) considers the entire time-course of the curve and does not assume that event risks are constant over the follow-up. This may be helpful to a more realistic interpretation of survival outcomes. In this letter, we re-analyzed the study curves of the CheckMate 577 trial by application of RMST. While confirming the disease-free progression benefits for nivolumab compared with placebo (28.54 months for the treatment arms versus 22.70 for the controls), our analysis allows us to interpret the survival benefit in a more conservative manner.