Bristol Myers Squibb (BMS) announced the US Food and Drug Administration (FDAP has approved Opdivo (nivolumab, injection for intravenous use) for 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 upon results from the recent Phase III CheckMate -577 trial, which evaluated the drug in comparison to placebo in esophageal or GEJ cancer patients with residual pathologic disease following neoadjuvant CRT and complete resection.
According to BMS, trial patients that received Opdivo in the trial exhibited median disease-free survival (mDFS) twice as long as in those who received placebo (22.4 months compared to 11 months. According to the trial results, Opdivo reduced the risk of disease recurrence or death by 31% compared to placebo.
In an exploratory analysis, among patients with adenocarcinoma, mDFS was 19.4 months with Opdivo versus 11.1 months with placebo. Also, among squamous cell carcinoma patients, mDFS was 29.7 months with Opdivo, compared to 11 months with placebo.
Ronan Kelly (director of the Baylor Scott and White Charles A Sammons Cancer Center, and W.W. Caruth Jr. Endowed Chair of Immunology at the Baylor University Medical Center) said, “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.”
Potential warnings and precautions associated with Opdivo include:
- severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, nephritis, and renal dysfunction, dermatologic adverse reactions, other immune-mediated adverse reactions
- infusion-related reactions
- complications of allogeneic hematopoietic stem cell transplantation (HSCT)
- embryo-fetal toxicity
- increased mortality in patients with multiple myeloma when Opdivo is added to a thalidomide analogue and dexamethasone (not recommended outside of controlled clinical trials.
“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 of US cardiovascular, immunology and oncology for BMS. “Today’s news marks an important step for patients as well as meaningful progress toward our commitment to pioneering immunotherapy treatment options in earlier stages of the disease where there is the potential to reduce the risk of recurrence.”
The application was reviewed under the FDA Real-Time Oncology Review (RTOR) pilot program, intended to ensure safe, effective treatments get to patients as quickly as possible. Another review was conducted under the Project Orbis initiative, enabling concurrent review by health authorities in Australia, Canada, and Switzerland.
CheckMate -577 was a Phase III, 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 study 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.
Bristol Myers Squibb is one of the industry companies scheduled to present on the Innovation Stage at BIO Digital, taking place online June 10-11 and June 14-18, 2021. Additionally, Elizabeth Mily (executive vice president of strategy and business development for BMS) will lead “Deal or No Deal? What to Know About Dealmaking Post-Pandemic” at the event on Tuesday, June 15, at 11:05 EDT. For more information, visit BIO.org.
