ATTRACTION-3 Confirms Nivolumab OS Benefit For Advanced Oesphageal Carcinoma

Author:  By Lynda Williams, Senior medwireNews Reporter

medwireNews: Nivolumab offers significantly better overall survival (OS) for patients with previously treated advanced oesophageal squamous cell carcinoma than paclitaxel or docetaxel chemotherapy, indicates research presented at the ESMO 2019 Congress in Barcelona, Spain. 

“Nivolumab might represent a new standard second-line treatment option to address the high unmet need for patients with advanced oesophageal squamous cell carcinoma”, the ATTRACTION-3 investigators say in a simultaneously published report in The Lancet Oncology. 

The phase III trial included patients with unresectable or recurrent disease who were refractory or intolerant to at least one fluoropyrimidine-based and platinum-based chemotherapy regimen and had a good ECOG performance status with a life expectancy of at least 3 months. 

The final analysis of the study was performed after a median 10.5 months of follow-up for OS for the 210 patients randomly assigned to receive nivolumab 240 mg every 2 weeks, and after a median of 8.0 months for the 209 patients who instead were given paclitaxel 10 mg/m2 on 6 out of every 7 weeks or docetaxel 75 mg/m2 every 3 weeks. 

Overall survival was significantly longer for the nivolumab-treated patients than those given chemotherapy at a median of 10.9 versus 8.4 months and a hazard ratio (HR) for death of 0.77, reported presenting author Byoung Chul Cho, from Yonsei University College of Medicine in Seoul, South Korea. 

Patients given nivolumab were more likely to be alive than those given chemotherapy at both 12 months (47 vs 34%) and 18 months (31 vs 21%), and prespecified subgroup analysis showed that median OS was 10.9 months regardless of whether tumour PD-L1 expression was at least 1% or less than 1%. 

Progression-free survival did not significantly differ between the nivolumab and chemotherapy arms (median 1.7 vs 3.4 months) but the researchers explain that the “[PFS] curves crossed and ultimately showed sustained separation favouring nivolumab beyond 5 months.” Indeed, nivolumab was associated with higher PFS rates at both 6 months (24 vs 17%) and 12 months (12 vs 7%).  

The objective response rate was also comparable in the nivolumab and chemotherapy arms (19 vs 22%), but the PD-1 inhibitor did achieve a longer duration of response (median 6.9 vs 3.9 months) and at data analysis patients given nivolumab were more likely to have an ongoing response (21 vs 6%). 

The researchers describe nivolumab as having a “favourable benefit–risk profile”, noting the PD-1 inhibitor was “well tolerated” with “numerically fewer” grade 3–4 treatment-related adverse events (18 vs 63%). Anaemia was the most common event at this severity with nivolumab at2% versus reduced neutrophil count with chemotherapy at 28%.  

Of the five treatment-related deaths, there was one death from interstitial lung disease and another from pneumonitis in the nivolumab group, while the chemotherapy arm had deaths from pneumonia, spinal cord abscess and interstitial lung disease. 

Finally, the team reports “significant, and at times, clinically meaningful, improvements in health-related quality of life with nivolumab versus chemotherapy”. Specifically, nivolumab significantly improved quality of life during treatment, and extended the time to deterioration of both quality of life (median 4.3 vs 2.7 months, HR=0.65) and utility index scores (4.2 vs 2.9 months, HR=0.73). 

In light of the ATTRACTION-3 findings, “[a] phase 3 study assessing nivolumab-based regimens versus chemotherapy in first-line treatment of patients with oesophageal squamous cell carcinoma is underway”, the team concludes. 

References 

Kato K, Cho BC, Takahashi M, et al. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label phase 3 trial. Lancet Oncol; Advance online publication 30 September 2019. https://doi.org/10.1016/S1470-2045(19)30626-6

Cho BC, Kato K, Takahashi M, et al. Nivolumab versus chemotherapy in advanced esophageal squamous cell carcinoma (ESCC): The phase III ATTRACTION-3 study. ESMO Congress 2019; Barcelona, Spain: 27 September–1 October. LBA11