Patients with recurrent oesophageal squamous cell carcinoma (ESCC) after frontline fluoropyrimidine and platinum-based combinations generally receive docetaxel or paclitaxel, which are associated with poor long-term survival. According to data from the phase III ATTRACTION-3 trial, reported at the ESMO Congress 2019 and in the Lancet Oncology, nivolumab is a promising agent for these patients.

In this trial, patients with ESCC (including adenosquamous carcinomas) were randomly assigned to receive either nivolumab (n = 210) or standard second-line chemotherapy (n = 209). At 17.6 months, the median overall survival (OS) durations were 10.9 months and 8.4 months, respectively (HR 0.77; P = 0.02). For patients receiving nivolumab, the median OS duration was the same regardless of the level of tumour expression of PD-L1 (<1% or ≥1%). With chemotherapy, median OS durations were 9.3 months for patients harbouring tumours with <1% PD-L1 expression and 8.1 months for those with ≥1% PD-L1.

The objective response rate was 19% with nivolumab and 22% with chemotherapy. Overall, nivolumab was associated with inferior progression-free survival (median 1.7 months versus 3.4 months with chemotherapy; HR 1.08), but a superior median duration of response (6.9 months versus 3.9 months).

The incidence of grade ≥3 treatment-related adverse events was 18% with nivolumab and 64% with chemotherapy; two fatalities in the nivolumab group and three with chemotherapy were deemed to be treatment-related. Health-related quality of life was assessed with a three-level questionnaire (EQ-5D-3L), with results favouring nivolumab over chemotherapy.

In July 2019, the FDA approved pembrolizumab for patients with advanced-stage ESCC expressing PD-L1 (combined positive score (CPS) ≥10) in the second-line setting and beyond. This approval was based on the OS results of the KEYNOTE-181 trial: median 10.3 months with pembrolizumab versus 6.7 months with chemotherapy (HR 0.64). Whether nivolumab will be approved for this indication irrespective of PD-L1 expression remains to be seen.