Treatment with Opdivo plus standard of care chemotherapy followed by maintenance Opdivo or Opdivo plus Yervoy failed to elicit survival benefits compared with standard of care chemotherapy alone in patients with previously untreated advanced biliary cancer, which is a rare form of liver cancer.
Adding Opdivo (nivolumab) to the standard of care chemotherapy regimen of gemcitabine and cisplatin or to the immunotherapy agent Yervoy (ipilimumab) did not improve survival outcomes compared with gemcitabine and cisplatin alone in a group of patients with previously untreated advanced biliary cancer, a rare form of liver cancer, according to recent study findings.
The data — which are published in the journal Cancer — demonstrated, however, that there may be a slight benefit to using Opdivo plus the standard of care regimen of gemcitabine and cisplatin followed by maintenance treatment with Opdivo every two weeks.
Of note, maintenance therapy is administered to patients after the primary treatment regimen is completed to limit the risk for disease recurrence.
Patients with advanced biliary tract cancer are typically treated with the chemotherapy combination of gemcitabine and cisplatin, according to the study authors. And although findings from prior studies have shown a six-month progression-free survival (time a patient remains free of disease progression during and after treatment) rate of 59% associated with the gemcitabine and cisplatin combination, the study authors noted that more is needed to improve outcomes from the “modest benefit” associated with the standard of care.
Moreover, the authors explained that the use of single-agent immune checkpoint inhibitors after disease relapse elicits minimal improvements in patients with advanced biliary tract cancer.
However, the investigators noted that single-agent immune checkpoint inhibitors have been successfully used as primary treatment alongside chemotherapy or other immune checkpoint inhibitors across other cancers.
Based on those findings, the authors wrote that they considered if the same treatment method would be beneficial in this patient population.
They conducted a multi-center trial that included 68 patients with advanced biliary cancer who had yet to receive any systemic therapies prior to enrollment. Patients were then randomized to receive a combination of Opdivo plus gemcitabine and cisplatin followed by a maintenance regimen of Opdivo (35 patients) or Opdivo plus Yervoy (33 patients).
The main goal of the trial was to determine if either treatment regimen bested the standard of care chemotherapy combination of gemcitabine plus cisplatin in terms of progression-free survival at six months. In this trial, the investigators used the previous finding of a six-month progression-free survival rate of 59% as a comparison and aimed to reach 80% in either treatment group.
At a median follow-up of 32.2 months, an analysis of the data showed that the six-month progression-free survival rate among patients who received Opdivo with gemcitabine and cisplatin followed by Opdivo was 59.4%. At a slightly shorter median follow-up — 31.5 months — the six-month progression-free survival rate among patients who received Opdivo and Yervoy was 21.2%.
The median overall survival (time from start of treatment to death from any cause) was 10.6 months in those who received the Opdivo plus chemotherapy combination and maintenance Opdivo and 8.2 months in the group administered Opdivo plus Yervoy. Prior research noted that the average overall survival for patients administered the gemcitabine/cisplatin combination was 11.7 months.
“Although (Opdivo plus Yervoy) was clearly inferior to the historical control, (Opdivo plus standard of care chemotherapy followed by (Opdivo) was similar in efficacy to standard treatment with gemcitabine and cisplatin and there was no obvious concern for increased toxicity or differences in secondary outcomes with the addition of (Opdivo) to chemotherapy, including median survival or response rate,” the study authors wrote.
For instance, investigators observed a two-year overall survival rate of 35.4% in the group that received Opdivo plus gemcitabine and cisplatin followed by maintenance Opdivo. Eleven patients within the group were still alive at the time of data cutoff.
These findings, according to the study authors, are a stark contrast to the estimated two-year overall survival rates of 15% to 22% in patients who received chemotherapy alone.
“This study found that whereas chemoimmunotherapy and dual immunotherapy in patients with advanced biliary cancer was generally well tolerated, neither treatment combination demonstrated an improvement in (progression-free survival) rate, median (progression-free survival), (overall survival) or response rate,” the authors concluded. “Nevertheless, at least one third of the patients were alive at two years in the chemoimmunotherapy (treatment group), and additional studies are ongoing to investigate this result, and importantly, evaluate biomarkers predictive for benefit from this treatment regimen.”
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