The approvals were announced by Bristol Myers Squibb (BMS), maker of the 2 immunotherapy treatments approved for 1 combination: nivolumab (Opdivo), the first approved PD-1 immune checkpoint inhibitor, and ipilimumab (Yervoy), which activates the immune system by targeting CTLA-4.
On May 27, FDA approved 2 combinations featuring nivolumab, including a dual immunotherapy combination, for first-line treatment for adult patients with unresectable, advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) regardless of PD-L1 status.
The approvals were announced by Bristol Myers Squibb (BMS), maker of the 2 immunotherapy treatments approved for 1 combination: nivolumab (Opdivo), the first approved PD-1 immune checkpoint inhibitor, and ipilimumab (Yervoy), which activates the immune system by targeting CTLA-4.1
FDA’s decision covers the use of the dual immunotherapy as well as a combination of nivolumab with fluoropyrimidine- and platinum-containing chemotherapy in these ESCC patients. According to the American Cancer Society, an estimated 20,640 new cases of esophageal cancer will be diagnosed in the United States in 2022, and 16,410 deaths will result from the disease in 2022 alone. 2
Treatments that include nivolumab are now approved for 5 indications in upper gastroesophageal cancers, according to BMS. “We recognize the need that exists for many patients facing upper gastroesophageal cancers, including advanced or metastatic esophageal squamous cell carcinoma, and we are focused on our goal to bring forward new treatment options with proven survival benefits regardless of PD-L1 status and histology,” Adam Lenkowsky, senior vice president and general manager, US Cardiovascular, Immunology, Oncology, Bristol Myers Squibb, said in the statement.
“Today’s approvals bring 2 first-line immunotherapy-based treatment options at once, [nivolumab]in combination with chemotherapy and [nivolumab plus ipilimumab] as the first dual immunotherapy option, to newly diagnosed patients with unresectable advanced or metastatic esophageal squamous cell carcinoma, further building on the role of [nivolumab]-based regimens in upper gastroesophageal cancers.”
Approval is based on results of the phase 3 CheckMate-648 trial,3 presented a year ago during the 2021 annual meeting of the American Society of Clinical Oncology. The trial examined nivolumab in combination with chemotherapy (321 patients) and nivolumab plus ipilimumab (325 patients), each compared with chemotherapy alone (324 patients).
Nivolumab plus chemo. Nivolumab with chemotherapy demonstrated superior overall survival (OS) compared with chemotherapy alone, both in all randomized patients, with a hazard ratio (HR) of 0.74 (95% CI: 0.61-0.90, P = .0021), and in patients whose tumors express PD-L1 (≥1%), HR 0.54 (95% CI: 0.41-0.71, P < .0001); the latter was a primary end point. In all randomized patients, the median OS was 13.2 months with nivolumab in combination with chemotherapy vs 10.7 months with chemotherapy alone; in patients whose tumors express PD-L1, median OS was 15.4 months for nivolumab with chemotherapy vs 9.1 months for chemotherapy alone.
Dual immunotherapy. The nivolumab-ipilimumab combination also improved OS compared to chemotherapy in all-randomized patients, a secondary endpoint, with HR 0.78 (95% CI: 0.65 to 0.95, P= .0110) and in patients whose tumors express PD-L1 (≥1%), a primary endpoint, with HR 0.64 (95% CI: 0.49-0.84, P= .0010). Median OS was 12.8 months with the immunotherapy combination vs 10.7 months with chemotherapy alone in all randomized patients and 13.7 months for the combination vs 9.1 months for chemotherapy alone for those with tumors that express PD-L1.
Adverse events. During the study, nivolumab and/or chemotherapy were stopped in 39% of patients and delayed in 71% due to adverse events (AEs); serious AEs occurred in 62% of patients taking nivolumab with chemotherapy. Most common serious AEs for those taking nivolumab with chemotherapy were pneumonia, dysphagia, esophageal stenosis (2.9%), acute kidney injury (2.9%), and pyrexia (2.3%). Five patients died during the study while being treated with nivolumab in combination with chemotherapy.
In the dual immunotherapy arm, nivolumab and/or ipilimumab were discontinued in 23% of patients; they were delayed in 46% of patients due to AEs. Serious AEs were seen in 69% of patients receiving nivolumab plus ipilimumab. The most frequent serious AEs in these patients were pneumonia, pyrexia, pneumonitis, aspiration pneumonia, dysphagia, abnormal hepatic function, decreased appetite, adrenal insufficiency, and dehydration (2.5%). Five patients died during the study while being treated with dual immunotherapy.
1. US Food and Drug Administration approves two Opdivo (nivolumab)-based regimens as first-line treatments for unresectable, advanced or metastatic esophageal squamous cell carcinoma. News Release. Bristol Myers Squibb. May 27, 2022. Accessed May 28, 2022. https://bit.ly/3wXcpdF
2. American Cancer Society. Key Statistics for Esophageal Cancer. https://www.cancer.org/cancer/esophagus-cancer/about/key-statistics.html. Updated January 12, 2022. Accessed May 28, 2022.
3. Chau I, Doki Y, Ajani JA, et al. Nivolumab plus ipilimumab or nivolumab plus chemotherapy versus chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma: first results of the CheckMate 648 study. J Clin Oncol. 2021;39:18_suppl abstr LBA4001. DOI: 10.1200/JCO.2021.39.15_suppl.LBA4001.