Abstract
Introduction: Nivolumab plus ipilimumab combination therapy has been administered as a first-line treatment in Japan since 2022 for patients with unresectable progressive or recurrent esophageal cancer. The efficacy and safety of this immune checkpoint inhibitor (ICI) doublet therapy are now being evaluated, and it is necessary to identify populations that benefit from this treatment at an early phase after initiation. For patients not showing early benefit, changing as soon as possible to other therapeutic strategies could improve their survival outcomes. Therefore, we attempted to identify decision-making factors such as early tumor shrinkage (ETS) based on treatment experience with ICI doublet therapy. Methods: The study included 19 patients who received nivolumab plus ipilimumab for non-surgically indicated or recurrent esophageal cancer between July 2022 and November 2023. Tumors were assessed approximately every 2 months after treatment initiation. The effects of ETS, depth of response (DpR), and clinicopathologic features, including immune-related adverse events (irAEs), on progression-free and overall survival were evaluated using Kaplan-Meier plots and Cox proportional hazard models. Results: The mean duration of ICI doublet administration was 5.89 months (range, 1–16 months). At first evaluation, patients who exhibited no tumor progression >20% indicated possible response to ICI doublet therapy, and patients whose tumors shrank even minimally exhibited favorable progression-free survival. Higher DpR at any cut-off line exhibited better progression-free survival than those with lower DpR. Fifteen patients experienced irAEs, with 13 of these patients experiencing irAEs within 3 months of treatment initiation. irAEs were associated with the efficacy of ICI doublet therapy, but efficacy could not be predicted based on early irAE experience. Conclusion: ETS-high, DpR-high, and irAEs might be associated with favorable responses to nivolumab plus ipilimumab. As a predictor of efficacy at an early phase, ETS >0% could be a deciding factor for continuing ICI doublet therapy.
Plain Language Summary
We studied the usefulness of evaluating early tumor shrinkage (ETS) as an efficacy predictor in patients with inoperable or recurrent esophageal cancer treated with nivolumab plus ipilimumab therapy. The immune checkpoint inhibitor (ICI) doublet therapy has been administered since 2022, and there are still not many patients who received this treatment all over the world. It is necessary to find well-responders to this treatment as soon as possible to improve outcomes and consider therapeutic strategies. We analyzed tumor shrinkage and clinicopathologic features in patients with inoperable or recurrent esophageal cancer treated with the treatment. ETS was defined as the percent decrease in the sum of the largest diameter of the target lesions at first evaluation after treatment initiation compared to that at baseline. Regarding ETS, those whose tumors shrank even minimally had favorable progression-free survival. Immune-related adverse events were also associated with the sensitivity and efficacy of ICI doublet therapy, but to find the efficacy at an early phase, ETS could be a decision-making factor for predicting the efficacy and continuation of ICI doublet therapy.
