US FDA approves Bristol Myers’ Opdivo as adjuvant treatment of completely resected esophageal or GEJ cancer in patients who have received n eoadjuvant CRT

Bristol Myers Squibb announced that the US Food and Drug Administration (FDA) has approved Opdivo (nivolumab, injection for intravenous use) for the adjuvant treatment of completely resected esophageal or gastroesophageal junction (GEJ) cancer with residual pathologic disease in patients who have received neoadjuvant chemoradiotherapy (CRT).

The approval is based on results from the phase 3 CheckMate -577 trial that evaluated Opdivo (n=532) compared to placebo (n=262) in esophageal or GEJ cancer patients with residual pathologic disease following neoadjuvant CRT and complete resection.

In the trial, among patients who received Opdivo, median disease-free survival (DFS) was twice as long as in those who received placebo (22.4 months [95% Confidence Interval [CI]: 16.6 to 34.0] compared to 11.0 months [95% CI: 8.3 to 14.3]). Opdivo reduced the risk of disease recurrence or death by 31% compared to placebo (Hazard Ratio [HR] 0.69; 95% CI: 0.56 to 0.85; P=0.0003).

In an exploratory analysis, among patients with adenocarcinoma (n=563, 70.9%), mDFS was 19.4 months (95% CI: 15.9 to 29.4) with Opdivo versus 11.1 months (95% CI: 8.3 to 16.8) with placebo (unstratified HR 0.75; 95% CI: 0.59 to 0.96), and among squamous cell carcinoma patients (n=230, 29%), mDFS was 29.7 months (95% CI: 14.4 to NE) with Opdivo versus 11.0 months (95% CI: 7.6 to 17.8) with placebo (unstratified HR 0.61; 95% CI: 0.42 to 0.88).
“Locally advanced esophageal and gastroesophageal junction cancers are aggressive tumor types that often require multiple approaches to address the disease, including chemotherapy, radiation and surgery,” said Ronan J. Kelly M.D., MBA., director, Baylor Scott & White Charles A. Sammons Cancer Center, and W.W. Caruth Jr. Endowed Chair of Immunology at Baylor University Medical Center. “Even after neoadjuvant CRT followed by surgery, there may be a high risk of recurrence for patients who do not achieve a pathologic complete response. In the CheckMate -577 trial, we saw a doubling in median disease-free survival compared to placebo, which suggests that Opdivo could become a new standard of care for these patients. This is exciting news, providing renewed hope.”

“Esophageal and GEJ cancer patients with residual pathologic disease following neoadjuvant CRT and complete resection face a high risk of disease recurrence; however, the predominant option for these patients has been surveillance,” said Adam Lenkowsky, senior vice president and general manager, US Cardiovascular, Immunology and Oncology, Bristol Myers Squibb. “This news marks an important step for patients as well as meaningful progress toward our commitment to pioneering immunotherapy treatment options in earlier stages of disease where there is the potential to reduce the risk of recurrence.”

This application was reviewed under the US FDA’s Real-Time Oncology Review (RTOR) pilot program, which aims to ensure that safe and effective treatments are available to patients as early as possible.10 The review was also conducted under the US FDA’s Project Orbis initiative, which enabled concurrent review by the health authorities in Australia, Canada and Switzerland.

CheckMate -577 was a phase 3 randomized, placebo-controlled, double-blind, multi-center trial, evaluating Opdivo as an adjuvant treatment in patients with esophageal or GEJ cancer with residual pathologic disease following neoadjuvant CRT and complete resection. The trial excluded patients who did not receive CRT prior to surgery, had stage IV resectable disease, autoimmune disease, or any condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone or equivalent) or other immunosuppressive medications.

The primary endpoint of the trial was DFS (investigator assessed). Following neoadjuvant CRT and complete tumor surgical resection (also known as trimodality therapy), a total of 794 patients were randomized to receive either Opdivo 240 mg (n=532) or placebo (n=262) by intravenous infusion every two weeks for 16 weeks, followed by Opdivo 480 mg or placebo by intravenous infusion every four weeks beginning at week 17. Treatment was until disease recurrence, unacceptable toxicity, or for up to one year in total duration.

The US FDA-approved dosing for Opdivo (injection for intravenous use) for adjuvant treatment of patients with resected esophageal or GEJ cancer is 240 mg intravenous infusion over 30 minutes every two weeks or 480 mg intravenous infusion over 30 minutes every four weeks until disease progression or unacceptable toxicity for a total treatment duration of one year.

Esophageal and gastroesophageal junction cancers are classified as upper gastrointestinal cancers. Esophageal cancer is a type of gastrointestinal cancer that starts in the inner layer of the esophagus (the mucosa) and grows. In the United States, it is estimated there will be approximately 19,260 new cases of esophageal cancer diagnosed and 15,530 deaths resulted from the disease in 2021. The two most common types of esophageal cancer are squamous cell carcinoma and adenocarcinoma.

The gastroesophageal junction (GEJ) is the area of the body that connects the lower part of the esophagus to the stomach. The prevalence of GEJ cancer has continued to rise.


Source:http://www.pharmabiz.com/NewsDetails.aspx?aid=138685&sid=2

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