Adjuvant Nivolumab Generates Long-Term DFS Benefit in Resected Esophageal/GEJ Cancer

Esophageal/GEJ Cancer |
Image by Ashling Wahner
& MJH Life Sciences Using AI

Five-year follow-up data from the phase 3 CheckMate 577 trial (NCT02743494) demonstrated that adjuvant nivolumab (Opdivo) maintained disease-free survival (DFS) and distant metastasis-free survival (DMFS) benefits compared with placebo in patients with resected esophageal cancer (EC) or gastroesophageal junction cancer (GEJC) following neoadjuvant chemoradiotherapy (CRT).1

Findings from the primary overall survival (OS) analysis did not reach statistical significance; however, the prolonged median OS and higher 5-year OS rates, coupled with an adjusted analysis accounting for subsequent therapies, suggest a clinically meaningful benefit.

The study, presented by Ronan J. Kelly, MD, MBA, FASCO, at the 2025 ASCO Annual Meeting, also highlighted PD-L1 combined positive score (CPS) ≥ 1 as a potential biomarker for enriching benefit in this early-stage setting. These results further solidify adjuvant nivolumab as a standard of care for resected esophageal or GEJ cancer with residual pathologic disease after neoadjuvant chemoradiation.

Findings from CheckMate 577 were initially presented at the 2020 ESMO Congress and demonstrated a statistically significant and clinically meaningful DFS benefit with nivolumab compared with placebo, effectively doubling the median DFS from 11 months to 22.4 months (HR, 0.69).2,3

“Based on these results, nivolumab was globally approved for the adjuvant treatment of patients with resected esophageal or GEJ cancer and, to date, remains the only approved immunotherapy in this setting,”Kelly, medical oncologist at Texas Oncology-Baylor Charles A. Sammons Cancer Center, said during the presentation.

Study Design and Key Findings

CheckMate 577 is a global, phase 3, randomized, double-blind, placebo-controlled trial. It enrolled 794 patients with stage II to III esophageal or GEJ adenocarcinoma or squamous cell carcinoma who had undergone R0 resection and had residual pathologic disease. Patients were randomly assigned 2:1 to receive nivolumab for 1 year or placebo. The primary end point was DFS, with OS as a secondary end point.1

At a median follow-up of 78.3 months (range, 60.1–96.6), the DFS benefit was sustained, with median DFS doubling from 10.8 months in the placebo arm to 21.8 months with nivolumab (HR, 0.76; 95% CI, 0.63-0.91; P =.1064). DMFS also favored nivolumab, with the median DMFS increasing from 14.6 months to 27.3 months (HR, 0.75; 95% CI, 0.62-0.90).

Overall Survival and Subgroup Analysis

The final analysis of OS showed a clinically meaningful improvement with nivolumab, extending median OS by 16.4 months and resulting in higher 5-year OS rates compared with placebo, although statistical significance was not met in the primary analysis. OS rates at 3 and 5 years with nivolumab vs placebo were 57% vs 50% and 46% vs 41%, respectively. The OS curves began to separate around 18 months, with a 5%-7% improvement in OS rates between the 3- and 5-year marks.

Subgroup analysis revealed trends toward OS benefit with nivolumab across most subgroups. Notably, the improvement was more pronounced in EC (HR, 0.69) compared with GEJC (HR, 1.14). For the first time in this setting, PD-L1 CPS emerged as an important factor: patients with PD-L1 CPS ≥ 1 showed an improvement in OS (HR, 0.79), while those with CPS < 1 derived little to no benefit (HR, 1.40).

Kelly cautioned that these subgroup analyses are exploratory due to small sample sizes.

Impact of Subsequent Therapy and Safety

An imbalance in subsequent anticancer therapy was observed, with 60% of patients in the placebo arm receiving it compared with 46% in the nivolumab arm, with a respective 5% and 15% going on to receive another line of immunotherapy. An ad hoc analysis adjusting for this confounding effect revealed an adjusted OS hazard ratio of 0.73, suggesting that the OS benefit was impacted by this imbalance.

In terms of safety, nivolumab was well tolerated, with most treatment-related adverse effects being grade 1 or 2. No treatment-related deaths occurred.

References

1. Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer (EC/GEJC) following neoadjuvant chemoradiotherapy (CRT): First results of overall survival (OS) from CheckMate 577. J Clin Oncol. 2025;43(suppl 16):4000. doi:10.1200/JCO.2025.43.16_suppl.4000
2. Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer (EC/GEJC): First results of the CheckMate 577 study. Ann Oncol. 2020;31(S1193-S1194):LBA9_PR. doi:10.1016/j.annonc.2020.08.2299
3. U.S. Food and Drug Administration approves Opdivo® (nivolumab) as adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer in patients who have received neoadjuvant chemoradiotherapy. News release. Bristol Myers Squibb. May 20, 2021. Accessed May 31, 2025. https://news.bms.com/news/details/2021/U.S.-Food-and-Drug-Administration-Approves-Opdivo-nivolumab-as-Adjuvant-Treatment-of-Completely-Resected-Esophageal-or-Gastroesophageal-Junction-Cancer-in-Patients-who-have-Received-Neoadjuvant-Chemoradiotherapy/default.aspx