Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: Initial results from the CheckMate 577 trial indicate a significant benefit with use of adjuvant nivolumab for stage II–III oesophageal and gastro-oesophageal junction cancer with residual pathological lymph node disease after neoadjuvant chemoradiotherapy and surgery.
“Nivolumab is the first adjuvant therapy to provide a statistically significant and clinically meaningful improvement in disease-free survival” in this patient population, reported Ronan Kelly, from Baylor University Medical Center in Dallas, Texas, USA, at the ESMO Virtual Congress 2020.
“These breakthrough results represent the first advance in many years for patients with operable oesophageal or gastro-oesophageal junction cancer, potentially establishing adjuvant nivolumab as a new standard of care for these difficult to treat tumours,” he said.
The trial participants had all received neoadjuvant chemoradiotherapy followed by R0 surgical resection at 4–16 weeks before randomisation to the trial: patients were assigned to receive nivolumab 240 mg every 2 weeks for 16 weeks, followed by 480 mg every 4 weeks for up to 1 year, or placebo.
The presenter emphasised that the 532 patients given nivolumab and the 262 given placebo were well balanced in terms of tumour histology (both 29% squamous cell carcinoma, 71% adenocarcinoma), disease stage at initial diagnosis (stage II, 34 vs 38%; stage III, 66 vs 62%), pathological lymph node status (ypN1 or poorer, 57 vs 58%) and PD-L1 tumour cell expression (≥1%, 17 vs 15%).
Median duration of treatment was 10.1 months with nivolumab versus 9.0 months with placebo, with the most common reasons for treatment discontinuation in these groups being treatment completion (43 vs 38%) and disease progression (28 vs 43%), respectively.
After a median 24.4 months of follow-up, the primary endpoint of the CheckMate 577 study was met, with median disease-free survival (DFS) doubling from 11.0 months with placebo to 22.4 months with nivolumab.
“Nivolumab provided a statistically significant and a clinically meaningful improvement in disease-free survival with a hazard ratio of 0.69 versus placebo, equating to a 31% reduction in the risk of disease recurrence or death with the use of nivolumab”, Ronan Kelly said.
Noting an “early and sustained separation of the disease-free survival curve”, he emphasized that “the placebo arm in this study reminds us that even following successful chemoradiation and an R0 surgical resection, those patients who do not achieve a pathological complete response have a high degree of disease recurrence in a relatively short period of time.”
Moreover, DFS analysis across prespecified subgroups “broadly favoured” nivolumab over placebo, regardless of histology, pathological lymph node status and PD-L1 expression, the presenter said.
Ronan Kelly also described nivolumab as being “well tolerated” with a similar rate of low and high grade adverse events to placebo. Serious treatment-related adverse events (TRAEs) at any grade occurred in 8% of nivolumab-treated patients versus 3% of controls, with grade 3–4 reported in 5% and 1%, respectively, and TRAEs leading to discontinuation in a corresponding 9% and 3%.
The most common TRAEs with potential immunological aetiology in the nivolumab arm were skin (24%), endocrine (17%) and gastrointestinal (17%) events, followed by hepatic (9%) and pulmonary (4%) symptoms. Less than 1% of nivolumab-treated patients experienced immune-related TRAEs at grade 3–4 – most commonly pneumonitis and rash at 0.8% each versus 0.4% each with placebo – and there were no grade 5 immune-related events.
Furthermore, patient-reported outcomes based on the EQ-5D-3L visual analogue scale and utility index showed “similar overall health status” over time between the two treatment groups, the presenter told delegates.
“Collectively, the safety and overall health status data support the use of nivolumab as an appropriate treatment in the adjuvant setting, where safety and tolerability are an important consideration”, Ronan Kelly concluded.
Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant nivoluamb in resected esophageal or gastroesophageal junction cancer (EC/GEJC) following neoadjuvant chemoradiation therapy (CRT): First results of the CheckMate 577 study. Ann Oncol; 31 (Suppl 4): S1142–S1215. DOI: 10.1016/annonc/annonc325.
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