European Society for Medical Oncology Congress

European Society for Medical Oncology Congress

Perspective from Andres Cervantes, MD, PhD
Perspective from David H. Ilson, MD, PhD
Source:

Kelly RJ, et al. Abstract LBA9_PR. Presented at: European Society for Medical Oncology Virtual Congress 2020; Sept. 19-21, 2020.

Disclosures: Bristol Myers Squibb supported the study. Kelly reports consultant/advisory roles with and research funding from Astellas, AstraZeneca, Bristol Myers Squibb, Cardinal Health, Eli Lilly & Co., Merck, Novartis, Ono Pharmaceutical, Pieris Pharmaceuticals and Takeda. Please see the abstract for all other researchers’ relevant financial disclosures.
September 29, 2020
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Nivolumab may be ‘new standard’ in esophageal, gastroesophageal junction cancers

Perspective from Andres Cervantes, MD, PhD
Perspective from David H. Ilson, MD, PhD
Source:

Kelly RJ, et al. Abstract LBA9_PR. Presented at: European Society for Medical Oncology Virtual Congress 2020; Sept. 19-21, 2020.

Disclosures: Bristol Myers Squibb supported the study. Kelly reports consultant/advisory roles with and research funding from Astellas, AstraZeneca, Bristol Myers Squibb, Cardinal Health, Eli Lilly & Co., Merck, Novartis, Ono Pharmaceutical, Pieris Pharmaceuticals and Takeda. Please see the abstract for all other researchers’ relevant financial disclosures.
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Adjuvant nivolumab significantly prolonged DFS compared with placebo among patients with resected esophageal and gastroesophageal junction cancer, according to results of the CheckMate 577 trial presented during ESMO Virtual Congress 2020.

Nivolumab (Opdivo, Bristol Myers Squibb), a PD-1 inhibitor, also demonstrated an acceptable safety profile.

Adjuvant nivolumab significantly prolonged DFS compared with placebo among patients with resected esophageal and gastroesophageal junction cancer.
Adjuvant nivolumab significantly prolonged DFS compared with placebo among patients with resected esophageal and gastroesophageal junction cancer.

“Neoadjuvant chemoradiation therapy followed by surgery, or trimodality therapy, is a widely used standard of care for patients with resectable locally advanced esophageal or gastroesophageal junction cancer. However, the risk for recurrence following trimodality therapy remains high, especially in patients with residual pathological disease for which there is no established adjuvant treatment,” Ronan J. Kelly, MD, MBA, oncologist at Charles A. Sammons Cancer Center at Baylor University Medical Center, said during a presentation.

Ronan J. Kelly, MD, MBA
Ronan J. Kelly

“Prior research has shown that nivolumab demonstrated superior survival in previously treated unresectable advanced or recurrent esophageal squamous cell carcinoma vs. chemotherapy and esophageal or gastroesophageal junction cancer vs. placebo," he added. "CheckMate 577 is the first global, randomized, double-blind, phase 3 trial to evaluate a checkpoint inhibitor in the adjuvant setting, after trimodality therapy, for esophageal and gastroesophageal junction cancer.”

The trial included 794 adults with stage II to stage III esophageal or gastroesophageal junction cancer.

Kelly and colleagues randomly assigned patients 2:1 to either 240 mg nivolumab (n = 532; median age, 62 years; 84% men; 81% white) or placebo (n = 262; median age, 61 years; 85% men; 82% white) once every 2 weeks for 16 weeks, followed by 480 mg nivolumab or placebo once every 4 weeks for a maximum treatment duration of 1 year.

All patients had received prior neoadjuvant chemoradiation and had residual pathologic disease. Researchers stratified patients based upon disease histology, pathologic lymph node status ( ypN1 vs. ypN0) and tumor cell PD-L1 expression ( 1% vs. 1%). Most patients (70%) had adenocarcinoma and nearly 60% had a pathologic lymph node status of ypN1 or greater.

DFS served as the primary endpoint.

Median follow-up for the prespecified interim analysis was 24.4 months (range, 6.2-44.9).

“The broad representation of geographical regions — including Europe, North America, Asia and the rest of the world — highlights the truly global nature of this study, which will continue as planned to allow for future analysis of the secondary endpoint of OS,” Kelly said.

Median duration of treatment was 10.1 months with nivolumab and 9 months with placebo.

Results showed a statistically significant and clinically meaningful improvement in DFS with nivolumab vs. placebo (median, 22.4 months vs. 11 months; HR = 0.69; 96.4% CI, 0.56-0.86), which corresponded to a 31% reduction in the risk for disease recurrence or death.

“Notably, there was an early and sustained separation of the DFS curves,” Kelly said. “The placebo group in this study reminds us that even following successful chemoradiation and an R0 surgical resection, patients who do not achieve a pathologic complete response have a high degree of disease recurrence in a relatively short period of time.”

Nivolumab conferred a DFS benefit across all prespecified subgroups —regardless of disease histology, pathologic lymph node status or tumor cell PD-L1 expression, Kelly added.

Eighty-nine percent of patients in the nivolumab group received treatment at a relative dose intensity of at least 90%.

Nivolumab appeared well-tolerated with an acceptable safety profile.

Treatment-related adverse events, mostly grade 1 or grade 2, occurred among 71% of patients in the nivolumab group and 46% of patients in the placebo group. The nivolumab group had a higher rate of serious treatment-related adverse events (8% vs. 3%) and events that led to discontinuation (9% vs. 3%). The most common reason for treatment discontinuation was treatment completion in the nivolumab group and disease progression in the placebo group.

“Nivolumab is the first adjuvant therapy to provide statistically significant and clinically meaningful improvement in DFS vs. placebo in resected esophageal and gastroesophageal junction cancer following neoadjuvant chemoradiation,” Kelly said. “The novelty of this study is highlighted by the fact that this is only the second tumor after melanoma where nivolumab has demonstrated a benefit in the neoadjuvant setting. These results represent the first advance in years for this group of patients, potentially establishing adjuvant nivolumab as a new standard of care.”