Efficacy of nivolumab in advanced esophageal carcinoma: A systematic review of phase III clinical trials.

Abstract

e16051 Background: Nivolumab (NIVO) is an IgG4 anti-PD-1 monoclonal antibody, approved against advanced esophageal carcinoma (EC). Our study aimed to analyze NIVO efficacy against advanced EC [esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC)] in phase III randomized clinical trials (RCTs). Methods: We collected data through a systemic search of major databases, using MeSH terms for esophageal carcinoma and nivolumab, through December 2024. Initial search yielded 387 articles. After excluding irrelevant articles, we included four phase III RCTs, reporting NIVO efficacy in EC. Results: A total of 2062 (EAC: 539, ESCC: 1533) patients were evaluated in 4 phase III RCTs: 1270 in NIVO and 792 in chemotherapy group (Table 1). Checkmate 649 evaluated NIVO + chemotherapy vs chemotherapy alone in advanced EAC [median follow-up:13.1 months (mo)]. NIVO + chemotherapy exhibited improved efficacy vs chemotherapy: objective response rate (ORR): 60% vs 40%, median overall survival (mOS): 12.3 vs 11.6 mo [hazard ratio (HR):0.84, 0.63-1.12], and median progression-free survival (mPFS): not achieved . Checkmate 648 evaluated 3 groups; NIVO + chemotherapy, NIVO + ipilimumab (IPI) and chemotherapy in untreated and unresected advanced ESCC (median follow-up: 13 mo). NIVO + chemotherapy showed favorable efficacy vs chemotherapy: ORR: 47% vs 27%, mOS: 13.2 vs 10.7 mo (HR: 0.74, 0.58-0.96), mPFS (HR: 0.81 (0.64-1.04). NIVO + IPI vs chemotherapy exhibited ORR: 28% vs 27%, mOS: 12.7 vs 10.7 mo (HR: 0.78, 0.62-0.98). ATTRACTION-3 analyzed NIVO vs chemotherapy in refractory ESCC (median follow-up of 36 mo). NIVO vs chemotherapy revealed; ORR: 19% vs 22%, mOS: 10.9 vs 8.5 (HR: 0.79, 0.62-0.96), and mPFS: not achieved. Checkmate 577 evaluated NIVO alone vs placebo in resected advanced EC, with a median disease-free survival of 22.4 vs. 11 months, HR: 0.69,0.56-0.96. On average, grade ≥3 treatment-related adverse events, mainly gastrointestinal and hematological were more prevalent in NIVO group. Conclusions: NIVO + chemotherapy compared with chemotherapy and NIVO alone, showed superior antitumor efficacy in advanced EC (EAC, ESCC) in terms of ORR and OS with a manageable toxicity profile, providing a benchmark for future studies. Trial ID/phase Regimen Patient number Histology Median age (year) Median follow-up (mo) Overall response rate (%) Overall survival (mo) Progression-free survival (mo) Adverse events, grade ≥3 (%) Checkmate 649/III NIVO + chemotherapy, chemotherapy 103, 108 EAC 63, 62 13.1 60, 40 12.3, 11.6 NA 59.2, 45.37 Checkmate 648/III NIVO + chemotherapy, chemotherapy 321, 324 ESCC 64, 64 13 47, 27 13.2, 10.7 5.8, 5.6 47, 36 NIVO plus Ipilimumab, chemotherapy 325, 324 ESCC 64, 63 13 28, 27 12.7, 10.7 NA 32, 36 Checkmate 577/III NIVO, placebo 311, 151 ESCC, EAC 62, 61 38.5 34, 32 Attraction/III NIVO, chemotherapy 210, 209 ESCC 64, 67 36 19, 22 10.9, 8.5 1.7, 3.4 18, 63 NA: not achieved, mo: months.