The programmed death (PD)-1 pathway plays a role in regulating host defenses that work to eliminate tumors.1 It has been linked to cancer treatment outcomes along with overall survival.1 Nivolumab is a PD-1 inhibitor that has improved survival rates when used to treat esophageal cancer.1 The CheckMate 648 study is a global phase 3 study that is evaluating nivolumab plus ipilimumab or nivolumab plus chemotherapy versus chemotherapy as a first-line treatment for advanced esophageal squamous-cell carcinoma (SCC). The first results of overall survival and progression-free survival from the CheckMate 648 study were presented at the American Society of Clinical Oncology 2021 annual meeting.
The CheckMate study recruited 970 adult participants with previously untreated advanced, recurrent, or metastatic esophageal SCC not able to be surgically removed. After molecular testing, 49% of the participants were found to have tumors harboring PD-ligand 1 (PD-L1) ≥1%. Participants were randomized to 3 groups: nivolumab (240 mg every 2 weeks) plus a chemotherapy protocol consisting of fluorouracil and cisplatin (every 4 weeks), nivolumab (3 mg/kg every 2 weeks) plus ipilimumab (1 mg/kg every 6 weeks), or chemotherapy alone. The primary study end points were overall survival and progression-free survival in the patients with PD-L1 harboring tumors. Secondary end points were overall survival and progression-free survival in all patients. Participants who received nivolumab plus chemotherapy and nivolumab plus ipilimumab had a significant overall survival improvement when compared with those who received chemotherapy alone. This was after 13+ months of follow-up for patients with PD-L1 ≥1 harboring tumors and for the randomized patients. Progression-free survival improvement was significant in participants with PD-L1 ≥1 harboring tumors who received nivolumab and chemotherapy versus chemotherapy alone. This did not reach significance cutoff when patients who received nivolumab and ipilimumab versus chemotherapy were compared.
The objective response rate in participants with tumors harboring PD-L1 ≥1% was 53% in the nivolumab and chemotherapy group; 35% in the nivolumab plus ipilimumab group; and 20% in the group who only received chemotherapy. When the objective response rate was analyzed in randomized participants, it was 47% in the nivolumab and chemotherapy group; 28% in the nivolumab plus ipilimumab group; and 27% in the group that only received chemotherapy. Durable objective responses were seen in groups treated with nivolumab when compared with the groups receiving chemotherapy alone. Safety data evaluation revealed an acceptable safety profile with low incidence of treatment-related deaths across the 3 groups.
Chau I, Doki Y, Ajani J, et al. Nivolumab (NIVO) plus ipilimumab (IPI) or NIVO plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced esophageal squamous cell carcinoma (ESCC): first results of the CheckMate 648 study. J Clin Oncol. 2021;39(18_suppl):LBA4001-LBA4001.
- Kato K, Doki Y, Ura T, et al. Long-term efficacy and predictive correlates of response to nivolumab in Japanese patients with esophageal cancer. Cancer Sci. 2020;111:1676-1684.