FDA Approves Adjuvant Nivolumab for Resected Esophageal and GEJ Cancer

The FDA approved adjuvant nivolumab (Opdivo) for the treatment of completely resected esophageal or gastroesophageal (GEJ) cancer with residual pathologic disease in patients who have previously had neoadjuvant chemoradiation treatment, according to Bristol Myers Squibb, the manufacturer of the immunotherapy agent.

"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, U.S. Cardiovascular, Immunology and Oncology, Bristol Myers Squibb in a statement. “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 disease where there is the potential to reduce the risk of recurrence.”¹

^{The approval is based on findings from the phase 3 CheckMate-577 trial (NCT02743494), which involved 794 patients with stage II esophageal or GEJ cancer, adenocarcinoma or squamous cell carcinoma. To be eligible, patients had to have undergone neoadjuvant chemoradiation and surgical resection and have residual pathologic disease and an ECOG performance score of 0 to 1.}

Study participants were randomized 2:1 to receive either 240 mg of nivolumab once every 2 weeks for 16 weeks then 480 mg once every 4 weeks; or placebo once every 2 weeks for 16 weeks and then once every 4 weeks. Treatment continued for up to 1 year.

Trial results proved that nivolumab led to a clinically meaningful improvement in disease-free survival (DFS) compared with placebo, 22.4 months versus 11.0 months, respectively in patients with resected esophageal or GEJ cancer after neoadjuvant chemoradiation.

There was also a 31% reduced risk of disease recurrence or death with nivolumab compared to placebo.

While patients were stratified based on histology (squamous or adenocarcinoma) pathologic lymph node status, and PD-L1 expression, benefit with nivolumab treatment was seen across all subgroups, also including age, sex, race, ECOG performance status, disease stage at initial diagnosis, and tumor location.

“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 MD, MBA, director, Baylor Scott & White Charles A. Sammons Cancer Center, and W.W. Caruth Jr. Endowed Chair of Immunology at Baylor University Medical Center.

While the majority of patients on nivolumab experienced an adverse event (AE) of any grade, far fewer 33% had a severe (grade 3 or 4) AE. Two percent of more of patients receiving nivolumab experience pneumonitis. One patient died of myocardial infarction while taking nivolumab.

Common AEs that were reported in 20% or more of patients were fatigue (34%), diarrhea (29%), nausea (23%), rash (21%), musculoskeletal pain (21%), and cough (20%).

“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.2,3,7 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.1,9 This is exciting news, providing renewed hope,” Kelly said.

Reference

Bristol Myers Squibb. U.S. Food and Drug Administration Approves Opdivo® (nivolumab) as Adjuvant Treatment of Completely Resected Esophageal or Gastroesophageal Junction Cancer in Patients who have Received Neoadjuvant Chemoradiotherapy. May 20, 2021. https://news.bms.com/news/details/2021/U.S.-Food-and-Drug-Administration-Approves-Opdivo-nivolumab-as-Adjuvant-Treatment-of-Completely-Resected-Esophageal-or-Gastroesophageal-Junction-Cancer-in-Patients-who-have-Received-Neoadjuvant-Chemoradiotherapy/default.aspx