Although trimodal therapy (neoadjuvant chemoradiation therapy followed by surgery) is the current standard, the risk of relapse is high, especially for 70% to 75% of patients who do not achieve a complete pathological response.
Between March 18th and 19th, SSO 2021 (International Conference on Surgical Cancer Care) took place in virtual format. At this event, it was presented the first data from CheckMate 577 (NCT02743494), a phase III, randomized, multicenter, double-blind trial evaluating the efficacy and safety of adjuvant nivolumab versus placebo in patients esophageal or resected gastroesophageal junction cancer, whose specimen after trimodal therapy (neoadjuvant chemoradiation therapy followed by surgery) has residual pathological disease.
In total, 794 patients were randomized at a 2:1 ratio to receive nivolumab 240mg (n = 532) or placebo (n = 262), once every 14 days for 16 weeks, followed by 480mg nivolumab or placebo every 4 weeks. The maximum duration of treatment was 1 year. The primary endpoint of the trial was disease-free survival (DFS), while overall survival (OS) and the rate of OS at 1, 2, and 3 years were secondary endpoints.
The majority of patients treated with nivolumab were male (84%), white (81%), with ECOG status 0 (58%), phase III disease (66%), adenocarcinoma histology (71%), whose anatomopathological endpoint was ypN1 or higher (60%). The average age was 62 years old. Additionally, 70% of patients had less than 1% of PD-L1 expression.
The mean follow-up was 24.4 months and the median duration of treatment with nivolumab was 10.1 months.
In the pre-planned interim analysis, patients treated with adjuvant nivolumab showed a statistically significant improvement in DFS compared to placebo (HR: 0.69; CI 96.4%: 0.56-0.86; P = 0.0003). Additionally, the use of nivolumab doubled the median DFS versus placebo (22.4 versus 11.0 months, respectively).
A subgroup analysis (including age, gender, ethnicity, ECOG, initial staging, histology, pathological lymph node status, PD-L1 expression, and time from complete resection to randomization) also demonstrated DFS superiority to nivolumab compared to placebo.
In total, 28% of patients discontinued treatment with nivolumab due to disease progression and 11% because of treatment-related adverse events (TRAEs). Most TRAEs were grade 1 or 2. TRAEs grade 3 or 4 with nivolumab and placebo occurred in 13% and 6% of patients, respectively; and included fatigue (1% vs<1%), diarrhea (<1% each), itching (<1% vs 0%) and skin rash (<1% each). Most TRAEs with potentially immuno–mediated etiology were of low grade, with grade 3 or 4 events occurring in less than 1% of patients in the nivolumab arm. There were no TRAEs grade 5.
Authors conclude that safety and efficacy data support the use of nivolumab as an appropriate adjuvant treatment. The trial will continue as planned to allow for a detailed future analysis of overall survival as a secondary endpoint.