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Expert Point of View: Rui-Hua Xu, MD, PhD


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David Cunningham, MD, Consultant Medical Oncologist, Head of the Gastrointestinal and Lymphoma Unit, and Director of Clinical Research at The Royal Marsden in London and Surrey in the United Kingdom, discussed CheckMate 6481 as well as the ESCORT-1st study of the PD-L1 inhibitor camrelizumab in advanced esophageal squamous cell carcinoma, whose “impressive” results were presented by Rui-Hua Xu, MD, PhD, of Sun Yet-Sen University in China.2

Rui-Hua Xu, MD, PhD

Rui-Hua Xu, MD, PhD

“These trials are just fantastic,” Dr. Cunningham said. “We’ve been doing research in gastroesophageal cancer for the past 20 years and have had so many trials that were negative. It’s not easy to move the dial on this disease, but I get a sense that we have seen that today…. We have new tools in the toolbox to approach this disease.”

Compared with chemotherapy alone in the first-line setting, the risk of death was significantly reduced by nivolumab/chemotherapy (hazard ratio [HR] = 0.54), nivolumab/ipilimumab (HR = 0.64), and camrelizumab/chemotherapy (HR = 0.70). In ESCORT-1st, median overall survival was 15.3 months with camrelizumab/chemotherapy and 12.0 months with chemotherapy alone (P = .001), and progression-free survival was improved (HR = 0.56; P < .001).

“CheckMate 648 and ESCORT-1st have remarkable similarities with respect to the relevant immunotherapy drug’s effect on survival and progression-free survival,” he said. The results establish the benefit of checkpoint inhibition plus chemotherapy in squamous cell cancer, as has been shown with adenocarcinoma in CheckMate 649, where nivolumab reduced deaths by 29% in patients with a combined positive score ≥ 5% (P < .0001),3 he said.He added that PD-L1 positivity indicates the “quantum of benefit” with this approach but “should not define patient selection.”

Although “chemotherapy may be important in some patients,” he said (based on some “early attrition” in the overall survival curve with nivolumab/ipilimumab), he noted that the longest duration of response was seen with the two checkpoint inhibitors: 11.8 months vs 8.4 months with nivolumab/chemotherapy and 5.7 months with chemotherapy. “Dual immunotherapy with nivolumab and ipilimumab offers patients a real alternative—a chemotherapy-free treatment, with long remissions in responding patients.”

Building upon the excellent outcomes in these trials, ongoing studies are evaluating dual checkpoint inhibition and the addition of antiangiogenic agents, he said. 

DISCLOSURE: Dr. Cunningham disclosed a financial relationship with Ovibio. Dr. Xu has served as a consultant or advisor to Bristol Myers Squibb, Merck Serono, Roche, Astellas, and AstraZeneca.

REFERENCES

1. Chau I, Doki Y, Ajani JA, et al: Nivolumab plus ipilimumab or nivolumab plus chemotherapy versus chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma. 2021 ASCO Annual Meeting. Abstract 4001. Presented June 5, 2021.

2. Xu RH, Luo H, Lu J, et al: ESCORT-1st: A randomized, double-blind, placebo-controlled, phase 3 trial of camrelizumab plus chemotherapy versus chemotherapy in patients with untreated advanced or metastatic esophageal squamous cell carcinoma. 2021 ASCO Annual Meeting. Abstract 4000. Presented June 5, 2021.

3. Moehler MH, Shitara K, Garrido M, et al: First-line nivolumab plus chemotherapy versus chemotherapy in advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma. 2021 ASCO Annual Meeting. Abstract 4002. Presented June 5, 2021.


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