Nivolumab improves OS in advanced oesophageal cancer

Positive results from the phase 3 ATTRACTION-3 trial, evaluating nivolumab vs chemotherapy (docetaxel or paclitaxel) for the second-line treatment of patients with unresectable advanced or recurrent oesophageal squamous cell carcinoma (ESCC) refractory or intolerant to combination therapy with fluoropyrimidine and platinum-based drugs, were presented by Prof. Byoung Chul Cho (Yonsei University College of Medicine, South Korea), in the Presidential Symposium [1] and simultaneously published in The Lancet Oncology [2].

ATTRACTION-3 is a phase 3, multicentre, randomised, open-label global study, although 96% of patients in both treatment arms were from Asia. Patients were treated until disease progression or unacceptable toxicity. A total of 419 patients were enrolled: 210 were allocated to nivolumab and 209 to chemotherapy.

For the primary endpoint of overall survival (OS), nivolumab demonstrated a statistically significant improvement over chemotherapy (see Table), with a 23% reduction in risk of death (HR 0.77; 95% CI 0.62-0.96; P=0.019) and a 2.5-month improvement in median OS (10.9 months; 95% CI 9.2-13.3) compared with patients treated with chemotherapy (8.4 months; 95% CI 7.2-9.9). The safety profile of nivolumab in this trial was consistent with previously reported studies in ESCC and other solid tumours.

Table. Results from the ATTRACTION-3 trial, which demonstrated superior OS and a favourable safety profile vs CT in pts with previously treated advanced ESCC, with survival benefit observed regardless of tumour PD-L1 expression



Table provided by ESMO

Patients treated in the nivolumab arm showed 12- and 18-month OS rates of 47% (95% CI 40-54) and 31% (95% CI 24-37), respectively, vs 34% (95% CI 28-41) and 21% (95% CI 15-27) among patients in the chemotherapy arm. Survival benefit with nivolumab was observed regardless of tumour PD-L1 expression levels. An exploratory analysis of patient-reported outcomes showed significant overall improvement in quality of life with nivolumab vs chemotherapy.

The objective response rates between the two arms were comparable at 19% (95% CI 14-26) among patients receiving nivolumab vs 22% (95% CI 15-29) among those receiving chemotherapy. However, the study showed nivolumab substantially increased the median duration of response for patients (6.9 months; 95% CI 5.4-11.1) vs 3.9 months (95% CI 2.8-4.2). In total, 7 patients in the nivolumab arm had ongoing responses at data cut-off compared with 2 patients in the chemotherapy arm. An overall HR of 1.08 (95% CI 0.87-1.34) suggested no meaningful difference in progression-free survival between the nivolumab and chemotherapy arms.

Fewer treatment-related adverse events (AEs) were reported with nivolumab vs chemotherapy, with a rate of 66% of any grade treatment-related AEs for patients receiving nivolumab compared with 95% for patients receiving chemotherapy. Patients in the nivolumab arm also experienced a lower incidence of grade 3 or 4 treatment-related AEs compared with those in the chemotherapy arm (18% vs 63%), and the percentage of patients experiencing treatment-related AEs leading to discontinuation was the same in both arms (9%).

“The significant survival benefit coupled with the favourable safety profile and patient-reported outcomes observed in this trial suggest nivolumab has the potential to represent an important new second-line treatment option for patients with advanced oesophageal squamous cell carcinoma, offering the possibility to extend their survival and improve their quality of life during treatment,” said Prof. Cho.

1. Cho BC et al. ESMO Congress 2019. Abstract LBA 11.
2. Kato K et al. Lancet Oncol. 2019 Sep 27. pii: S1470-2045(19)30626-6.

Posted on 26 November, 201927 March, 2024