In 2021, Esophageal Cancer patients and advocates celebrated the Food and Drug Administration’s approval of immunotherapies for patients with advanced Gastroesophageal Cancer, Esophageal Adenocarcinoma, and Esophageal Squamous Cell Carcinoma.
Those approvals included all patients regardless of the level of their cancer’s PD-L1 expression, even though the studies supporting approval of the immunotherapies found that patients with higher PD-L1 expression had better outcomes. PD-L1, or programmed death ligand 1, is a protein that regulates the immune system’s response, acting as a kind of “brake” to keep the body’s immune responses under control.
Vote to Restrict Access
Despite testimony from some of the nation’s top Esophageal Cancer researchers, this week, the Food and Drug Administration’s Oncologic Drugs Advisory Committee (ODAC) voted to restrict availability of checkpoint-inhibiting immunotherapies Keytruda (pembrolizumab) by Merck and Opdivo (nivolumab) by Bristol-Myers Squibb as first-line therapy (in combination with chemotherapy) for patients with HER-2 negative Advanced Gastroesophageal Junction cancer and Her-2 negative Esophageal Squamous Cell Carcinoma. The panel voted to recommend that the therapies should only be available to patients whose cancer expresses the protein PD-L1 at levels equal to or greater than 1.
The recommendation would also apply to the use of Tevimbra (tislelizumab) by BeiGene, if it is approved for use in these patients. The FDA is expected to decide in December whether to approve the use of Tevimbra in patients with Gastroesophageal Adenocarcinoma and Esophageal Squamous Cell Carcinoma.
Patients and Advocates Spoke Out
The panel heard testimony from eight patients, caregivers, and advocates requesting that the immunotherapies be widely available to all patients originally included in the FDA approval of the drugs in 2021 including ECAN’s CEO Mindy Mintz Mordecai and Esophageal Cancer patient Kimberly Wilson.
Ms. Wilson described her battle with Esophageal Cancer which progressed to Stage IV after esophagectomy.
Esophageal Cancer patient Kimberly Wilson testifies during ODAC meeting, Sept. 26, 2024.
ECAN’s Mindy Mintz Mordecai told the panel that restricting access to these immunotherapies will cause some patients to lose hope. She pointed to testimony that indicated that the scoring used to determine PD-L1 status was not reliable nor uniform.
ECAN President & CEO Mindy Mintz Mordecai testifies during ODAC meeting, Sept. 26, 2024
After a morning meeting, the panel considering restrictions for patients with Gastroesophageal Junction and Gastric Cancer voted 10 to 2 to limit access to checkpoint inhibitors. At the end of the afternoon session, the panel considering access to the drug for patients with Esophageal Squamous Cell Carcinoma (ESCC), approved the restriction by a vote of 11 to 1.
Concern that Data Doesn’t Answer the Question
Dr. Ravi Madan of the National Cancer Institute in Bethesda, Maryland, abstained on both votes saying, “I’m just not fully convinced that this is the dataset that should be used to address the question of, ‘Is this the cutoff required to bring about benefit versus risk?'” he said. “We don’t know. We never really went into these studies asking this question. That’s where I have some trouble; that is, I’m not sure that we have the power in this dataset. We’re trying our best to glean what we can from existing data that was never really designed to answer this question.”
Lone No Vote
Dana Deighton, the patient representative on the ESCC panel was the only vote against the change. She said, “I believe in the Hail Mary pass. Sometimes things happen, and you don’t know why.” Ms. Deighton is a member of the ECAN Board of Directors.
Potential for PD-L1 Negative Patients to Receive the Drug for Free?
Dr. Richard Pazdur, the director of the FDA’s Oncology Center of Excellence, urged the representatives of Merck, Bristol-Myers Squibb, and BeiGene to extend compassionate use or expanded use protocols to provide the immunotherapies free of charge to PD-L1 negative patients who desire the treatment. The drugmakers did not commit to expanding their existing compassionate use programs, but gave a generally positive response. Dr. Pazdur indicated he would follow up to see that they do.
“I do want to address the concerns of patients. We realize the issues here with the biopsy, etc.,” he said. “If we do restrict it and if somebody wants the drug, it probably would not be paid for. So, we want to make our views patient-centric so that there might be other avenues that patients may have access to this drug.”
Watch full testimony of the Esophageal Cancer advocates here.
Esophageal Cancer patient Kimberly Wilson testifies during ODAC meeting, Sept. 26, 2024.
ECAN President & CEO Mindy Mintz Mordecai testifies during ODAC morning meeting, Sept. 26, 2024
ECAN President & CEO Mindy Mintz Mordecai testifies during ODAC afternoon meeting, Sept. 26, 2024.