The U.S. Food & Drug Administration has granted Priority Review for the use of immunotherapies in three new designations for patients with Esophageal Cancer.  FDA Priority Review speeds up the review of therapies so that decisions will be made within six months vs. the ten months a standard review would take and are given for drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.

Potential Immunotherapy for Previously Untreated Esophageal Cancer Patients

Both Keytruda (pembrolizumab) and Opdivo (nivolumab) are being considered for a first-line therapy designation in combination with chemotherapy for patients with advanced or metastatic Esophageal Cancer. If approved, this would mean that for the first time, Esophageal Cancer patients would not have to experience disease progression on other treatments before getting the chance to receive immunotherapy.

First-Line Opdivo (Nivolumab) plus Chemo for Advanced, Metastatic Esophageal Cancer

Opdivo (nivolumab) is being considered for approval as first-line therapy for patients with metastatic or advanced Esophageal Cancer in combination with fluoropyrimidine- (5 FU) and platinum-containing chemotherapy.  This application is based on the results of the Checkmate-649 study which included patients with previously untreated, non-HER2-positive advanced or metastatic gastroesophageal junction cancer or esophageal adenocarcinoma.

Researchers assigned patients to nivolumab plus chemotherapy (FOLFOX), nivolumab plus ipilimumab (Yervoy) an anti-CTLA-4 monoclonal antibody, or chemotherapy alone. The nivolumab-chemotherapy regimen significantly improved overall survival and progression-free survival among patients whose tumors expressed programmed death ligand-1 (PD-L1 – the checkpoint target of Opdivo) with a combined positive score of 5 or higher. Researchers also reported a significant overall survival benefit with the combination in the overall study population.

Watch ECAN’s interview with the Lead Investigator of the Checkmate-649 study.

The FDA is expected to issue its decision on this application by May 25th.

First-Line Keytruda (Pembrolizumab) plus Chemo in Locally Advanced, Unresectable or Metastatic Esophageal Cancer

The FDA will decide on the efficacy of Keytruda (pembrolizumab), another PD-LI inhibitor, in combination with chemotherapy in patients with previously untreated advanced esophageal squamous cell carcinoma, esophageal adenocarcinoma, or esophagogastric junction adenocarcinoma.  The application for approval is based upon the Keynote-590 study which found that overall survival was improved for all patients who received Keytruda with chemotherapy rather than chemotherapy alone.

Benefits were greatest in patients with high expression of programmed death ligand-1 (PD-L1), the check-point target of Keytruda.  Patients with a PD-L1 combined positive score of 10 or more experienced the greatest benefit from the addition of Keytruda to their chemotherapy.

A decision on this application is expected by April 13th.

Opdivo for Patients who Have Undergone Esophagectomy after Chemoradiation

Esophageal Cancer patients who undergo esophagectomy but fail to achieve a pathologic complete response are at substantial risk for recurrence of their disease.  The Checkmate-577 study provided Opdivo (nivolumab) to Esophageal Cancer patients who had undergone chemoradiation and esophagectomy but did not achieve a pathologic complete response.  When compared to patients who did not receive Opdivo, progression-free survival was doubled and the risk of recurrence or death was reduced by 31% in the group that received Opdivo.

The National Cancer Institute defines pathologic complete response as a “lack of all signs of cancer in tissue samples removed during surgery or biopsy after treatment with radiation or chemotherapy. To find out if there is a pathologic complete response, a pathologist checks the tissue samples under a microscope to see if there are still cancer cells left after the anticancer treatment.” The number of Esophageal Cancer patients who achieve a pathologic complete response after esophagectomy is relatively low.

Watch ECAN’s interview with the Lead Investigator of the Checkmate-577 study.

An FDA decision is expected by May 20th on this application for treating patients who have undergone esophagectomy with Opdivo.

Keytruda & Opdivo are Approved for Treatment of Previously Treated Esophageal Squamous Cell Carcinoma

The FDA approved Keytruda for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 with a score of 10 or higher after they have experienced disease progression on one or more prior lines of systemic therapy.

The FDA approved Opdivo for the treatment of patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma regardless of their PD-LI expression who have already received fluoropyrimidine- and platinum-based chemotherapy.