Adjuvant nivolumab does not have a detrimental effect on the quality of life of patients with resected esophageal or gastroesophageal junction cancer
Previously reported results of the CheckMate 577 trial support the use of adjuvant nivolumab in patients with resected esophageal or gastroesophageal junction cancer (EC/GEJC) after neoadjuvant chemoradiotherapy (CRT) and surgery (HR[96.4%CI]: 0.69 [0.56-0.86], P= 0.0003). During ASCO GI 2021, health-related quality of life (HRQoL) and patient reported outcome (PRO) data of this trial were presented further supporting the use of adjuvant nivolumab in this setting.
For EC/GEJC, the risk of recurrence has classically remained high even after neoadjuvant CRT and resection. Recently, the phase III KEYNOTE-577 trial has demonstrated the efficacy of adjuvant nivolumab in this setting, finding a median disease free survival (DFS) that was doubled when compared to placebo (22.4 vs. 11.0 months) (HR[96.4%CI]: 0.69[0.56-0.86], P= 0.0003). nivolumab also had a manageable safety profile, with only 9% of patients discontinuing the treatment with nivolumab due to treatment-emergent adverse events (TEAEs) (vs. 3% with placebo).
CheckMate 577 randomised (2:1) 794 stage II/III EC/GEJC patients, who had been given prior neoadjuvant CRT and resection, to receive nivolumab 240 mg every 2 weeks for 16 weeks, followed by nivolumab 480mg every 4 weeks, for a total treatment duration of 1 year, or placebo at the same dosing schedule. Health-related quality of life (HRQoL) factors such as disease-related symptoms, mental and physical well-being, and overall QoL were also assessed using the FACT-E and EQ-5D-3L questionnaires. Descriptive statistics were used to assess patient reported outcome (PRO) change from baseline over 12 months, with mixed model for repeated measures and time to deterioration analyses evaluating the difference between treatment with nivolumab and placebo. Collected at baseline, every 4 weeks during the 1-year treatment phase, and up to 2 years post-treatment, the results of these PROs were reported at ASCO GI 2021.
Increased HRQoL observed in both treatment arms
Questionnaire uptake was high, with PRO completion rates of >95% at baseline and 90% over the 12 month treatment period. At baseline, the mean HRQoL scores were similar across both treatment arms for FACT-E total score (nivolumab: 133.6 [20.8]; placebo: 134.4 [20.4]), esophageal cancer subscale (ECS; nivolumab: 50.3 [9.2]; placebo: 50.2 [8.9]), EQ-5D Visual Analogue Scale (nivolumab: 70.4 [22.4]; placebo: 69.2 [23.9]); and EQ-5D Utility Index (nivolumab: 0.820 [0.180]; placebo: 0.831 [0.162]). Although there was a general trend for an increased HRQoL, oesophageal-specific items and EQ-5D-3L from baseline to week 53 in both treatment arms, these changes did not reach clinically meaningful thresholds for improvement. In contrast, statistically significant, but clinically less meaningful differences were observed between nivolumab and placebo for ECS (NIVO: 2.1; PBO: 3.3; Change: -1.2, P= 0.002) and trial outcome index (nivolumab: 2.7; placebo: 4.7; Change: -2.0, P= 0.033). These findings were consistent in all investigated subgroups. The time to first deterioration of HRQoL did not differ significantly between the two treatment arms in either PRO questionnaire, and no significant differences were observed in the subgroup analysis.
In summary, HRQoL results from CheckMate 577 demonstrate that stage II/III EC/GEJC patients who were treated with either nivolumab or placebo showed improvements in HRQoL from baseline. As such, patients treated with adjuvant nivolumab, did not experience a reduction in HRQoL outcomes. There was also no significant difference in the time to a first deterioration in HRQoL between the two treatment arms. These findings, in combination with the previously reported DFS benefit and safety profile, support the use of nivluamb as an adjuvant treatment strategy in this setting.
Cutsem V E et al., Checkmate 577: Health-related quality of life (HRQoL) in a randomized, double-blind phase III study of nivolumab (NIVO) versus placebo (PBO) as adjuvant treatment in patients (pts) with resected esophageal or gastroesophageal junction cancer (EC/GEJC). Presented at ASCO GI 2021; Abstract 167.