Nivolumab Combinations Deliver 5-Year Survival Advantage in Advanced Esophageal Cancer

Nivolumab (Opdivo; Bristol Myers Squibb) plus chemotherapy and nivolumab plus ipilimumab (Yervoy; Bristol Myers Squibb) led to improved long-term survival benefit, sustained responses, and favorable safety compared with chemotherapy in patients with advanced esophageal squamous cell carcinoma (ESCC). The 5-year follow-up data are to be presented at the European Society of Medical Oncology 2025 Congress.

ESCC

In 2025, the American Cancer Society estimated over 22,000 new cases of ESCC, resulting in more than 16,000 deaths. In the United States, ESCC is less common and only makes up about 1% of all cancer diagnoses; however, it is more prevalent in other regions, such as Iran, northern China, India, and southern Africa. Patients with ESCC have a 5-year survival rate of about 49% for localized disease.

Patients diagnosed with ESCC are more likely to be men over the age of 55, with an average age of diagnosis at 69 years. Women can also develop ESCC and have a lifetime risk, with about 1 in 437 women being at risk compared with 1 in 132 men. Risk varies across patients depending on age, alcohol or tobacco use, presence of gastroesophageal conditions such as reflux or Barrett’s esophagus, higher body weight, diet and exercise, and genetics, among other factors.

Novel therapies greatly improve outcomes for patients with ESCC, but continued advancement in treatment approaches is critical. Nivolumab, a fully human antibody targeting PD-1, works by reactivating antitumor T-cell activity. When paired with chemotherapy—which can further stimulate immune response—this combination shows significant efficacy in treating patients with non–small cell lung cancer.

In the phase 3 CheckMate 648 (NCT03143153) trial, nivolumab combined with chemotherapy and nivolumab plus ipilimumab—globally approved combinations—yielded clinically meaningful 5-year survival outcomes for patients with advanced ESCC.

CheckMate 648

The trial involved 970 patients randomized to 1 of 3 arms. Patients in arm 1 received 240 mg of nivolumab every 2 weeks and chemotherapy consisting of fluorouracil plus cisplatin every 4 weeks. In arm 2, patients received 3 mg/kg of nivolumab every 2 weeks plus 1 mg/kg of ipilimumab every 6 weeks. Arm 3 was treated with the chemotherapy regimen.

The primary end points were overall survival (OS) and progression-free survival (PFS) according to blinded independent central review in patients with tumor cell (TC) PD-L1 greater than or equal to 1%.

With a minimum follow-up of 61 months, treatment with nivolumab plus chemotherapy and nivolumab plus ipilimumab continued to demonstrate OS benefits and higher 5-year OS rates compared with chemotherapy alone. This was observed in patients with TC PD-L1 expression greater than or equal to 1% and in the overall randomized population.

Objective response rates (ORR) were approximately 53% and 35% with nivolumab plus chemotherapy and nivolumab plus ipilimumab, respectively, compared with 20% for chemotherapy alone in patients with TC PD-L1 greater than or equal to 1%. In the overall study population, ORR was 47% and 27% with these respective regimens versus 27% for chemotherapy alone.

Median duration of response (DOR) remained longer with nivolumab plus chemotherapy and nivolumab plus ipilimumab compared with chemotherapy alone. Among patients with TC PD-L1 greater than or equal to 1%, median DOR was 8.4 months (95% CI 6.9–12.4) and 11.8 months (95% CI 6.8–18.0) for nivolumab plus chemotherapy and nivolumab plus ipilimumab, respectively, versus 5.7 months (95% CI 4.4–8.7) for chemotherapy alone. In all randomized patients, median DOR was 8.2 months (95% CI 6.9–9.7) and 11.1 months (95% CI 8.3–14.3) versus 6.9 months (95% CI 5.7–7.7), respectively.

At 5 years, 5% and 19% of patients with TC PD-L1 greater than or equal to 1% treated with nivolumab plus chemotherapy and nivolumab plus ipilimumab, respectively, remained in response, compared with 0% for chemotherapy alone. Among all randomized patients, 14% and 17% compared with 3%, respectively, remained in response at 5 years. Notably, the researchers reported no new safety signals.

“Nivolumab plus chemotherapy and nivolumab plus ipilimumab demonstrated long-term survival benefit and more durable responses vs chemotherapy, and acceptable safety, after 5 years of follow-up,” the researchers wrote in the abstract. “These results continue to support [the combination] as first-line treatments for advanced ESCC.”

REFERENCES

1. Key Statistics for Esophageal Cancer. American Cancer Society. Updated August 14, 2025. Accessed October 15, 2025. https://www.cancer.org/cancer/types/esophagus-cancer/key-statistics.html

2. Causes, risk factors, and prevention of esophageal cancer. American Cancer Society. Updated August 14, 2025. Accessed October 15, 2025. https://www.cancer.org/cancer/types/esophagus-cancer/causes-risks-prevention.html

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4. Halpern L. Neoadjuvant nivolumab with chemotherapy yields significant overall survival benefit in resectable NSCLC. Pharmacy Times. June 9, 2025. Accessed October 15, 2025. https://www.pharmacytimes.com/view/neoadjuvant-nivolumab-with-chemotherapy-yields-significant-overall-survival-benefit-in-resectable-nsclc

5. A study to evaluate efficacy in subjects with esophageal cancer treated with nivolumab and ipilimumab or nivolumab combined with fluorouracil plus cisplatin versus fluorouracil plus cisplatin (CheckMate 648). Clinicaltrials.gov. Updated February 25, 2025. Accessed October 15, 2025. https://clinicaltrials.gov/study/NCT03143153

6. Chau I, Ajani J, Doki Y, et al. 2106P - Nivolumab (NIVO) plus chemotherapy (chemo) or ipilimumab (IPI) vs chemo as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC): 5-year follow-up from CheckMate 648. Presented at: European Society of Medical Oncology 2025 Congress. October 17, 2025, to October 18, 2025. Abstract 2160P