NEW YORK (Reuters Health) – When esophageal or gastroesophageal-junction cancer remains a threat after chemoradiotherapy and surgery because of residual pathological disease, treatment with the checkpoint inhibitor nivolumab doubles disease-free survival, according to the results of the large international CheckMate 577 trial.
Median disease-free survival times were 11.0 months with placebo and 22.4 months with the drug, made by Bristol Myers Squibb and Ono Pharmaceutical. The companies paid for the study.
That translates to a 31% reduction (P<0.001) in the risk of death or recurrence. Overall survival is still being determined.
“This is the first study to show this works in early-stage disease,” said chief author Dr. Ronan Kelly of Baylor University Medical Center in Dallas, Texas.
“This is a very significant paper and should be practice-changing,” Dr. William Cance, chief medical and scientific officer of the American Cancer Society, told Reuters Health by phone. “It also shows that esophageal cancer is responsive to immunotherapy, which is a good sign.”
“Although overall survival data are not mature, the doubling of median disease-free survival will almost certainly translate into an overall survival benefit,” Dr. David Ilson of the Memorial Sloan Kettering Cancer Center in New York writes in an editorial in The New England Journal of Medicine, where the study was published. “The trial shows the first true advance in the adjuvant therapy of esophageal cancer in recent years and will become a new standard of care.”
Based on the results, adjuvant nivolumab therapy for these patients was incorporated into the National Comprehensive Cancer Network practice guidelines in December.
“We are awaiting (U.S. Food and Drug Administration) approval but by being listed in the NCCN guidelines, treating physicians have already started using this as a new standard-of-care approach,” Dr. Kelly, director of oncology at the Charles A. Sammons Cancer Center at Baylor, told Reuters Health by email.
The treatment, also used for kidney, liver, lung and a host of other cancers, is designed to block the cancer’s defense mechanism against the immune system. It costs about $165,000, according to prices on goodrx.com. Bristol Myers Squibb sells it under the brand name Opdivo.
Dr. Kelly said that with results of the drug against bladder cancer and early-stage lung cancer due soon, “we are seeing a movement to use these immunotherapy drugs in an operable disease setting rather than waiting for metastatic disease.”
Esophageal cancer kills more than a half million people worldwide each year. It is the seventh most common type of tumor.
After chemoradiotherapy and esophageal surgery, the pathological cure rate is only about 20% to 30%, depending on the subtype, according to Dr. Cance.
All of the 532 volunteers in the CheckMate study had resected stage-II or -III disease and residual pathological disease. More than half had lymph node-positive disease. Most had adenocarcinoma or squamous-cell carcinoma.
Beginning four to 16 weeks after surgery, the patients were treated every two weeks for 16 weeks, then every four weeks for a total of one year. Median follow-up was 24.4 months. Volunteers were checked for recurrence every 12 weeks using CT scans or MRI.
Better disease-free survival with nivolumab was seen regardless of whether patients had adenocarcinoma or squamous-cell carcinoma, their disease stage at diagnosis, their age, their gender or race. It was also independent of tumor-cell PD-L1 expression.
However, the trends were better for squamous-cell-cancer patients, those with node-negative disease and patients with esophageal tumors versus those at the junction with the stomach.
“The risk of distant recurrence or death was 26% lower with nivolumab than with placebo,” Dr. Kelly and his colleagues report.
Thirty percent of nivolumab recipients received subsequent therapy versus 42% who got placebo.
The rates of grade-3 or -4 adverse events believed to be due to the treatment regimen were 13% with nivolumab and 6% with placebo.
The most common side effects were fatigue, diarrhea, rash and pruritus, although diarrhea and fatigue were common in placebo patients as well.
Nine percent of patients went off the drug because of perceived adverse events versus 3% of placebo.
The vast majority of patients said they were bothered by the side effects of treatment only a little bit or not at all.
“The side-effects are much more tolerable than chemotherapy and radiation,” Dr. Kelly said. “We know how to manage all the potential side effects.”
SOURCE: https://bit.ly/3w1RxAx and https://bit.ly/31v5s3X The New England Journal of Medicine, online March 31, 2021.
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