Nivolumab demonstrated superior overall survival versus chemotherapy in patients with previously treated esophageal squamous cell carcinoma, according to ATTRACTION-3 data. At ASCO 2021, immunotherapy efficacy data were released in the first–line setting of Checkmate 648.
During ASCO World Congress 2021, it was presented the initial overall survival (OS) and progression-free survival (PFS) data from CheckMate 648 (NCT03143153), the first global, randomized, phase III trial, evaluating nivolumab + ipilimumab or nivolumab combined with fluorouracil + cisplatin versus fluorouracil + cisplatin in individuals with previously untreated advanced non-resectable, recurrent, or metastatic esophageal squamous cell carcinoma (SCC).
Patients were randomized to nivolumab (240mg every two weeks) + chemotherapy (fluorouracil + cisplatin every four weeks); nivolumab (3mg/kg every two weeks) + ipilimumab (1mg/kg every six weeks); or chemotherapy alone. Primary endpoints for both comparations were OS and PFS by blind independent central review (BICR) in patients with PD-L1 expression ≥ 1% in tumor cells. Secondary endpoints tested hierarchically included OS and PFS in all randomized patients.
In total, 970 patients were randomized to receive nivolumab + chemotherapy, nivolumab + ipilimumab and chemotherapy (49% of them with PD-L1-positive). After a minimum follow-up of 13 months, nivolumab + chemotherapy was higher in OS versus chemotherapy (15.4 versus 9.1 months; HR 0.54; CI 99.5% 0.37 – 0.8; P < 0.0001), as well as nivolumab + ipilimumab versus chemotherapy (13.7 versus 9.1 months; HR 0.64; CI 98.6% 0.46 – 0.9; P = 0.001) in patients with PD-L1 ≥ 1%. There was also a gain in OS in the overall randomized population, with 13.2 versus 10.7 months in favor of nivolumab + chemotherapy (HR 0.74; CI 99.1% 0.58 – 0.96; P = 0.0021) and 12.8 versus 10.7 months in favor of nivolumab + ipilimumab (HR 0.78; CI 98.2% 0.62 – 0.98; P = 0.011) when compared to chemotherapy alone.
A statistically significant benefit for PFS was also observed for nivolumab + chemotherapy versus chemotherapy (HR 0.65; CI 98.5% 0.46 – 0.92; P 0.0023) in patients with PD-L1 ≥ 1%. However, the PFS for nivolumab + ipilimumab versus chemotherapy in patients with PD-L1-positive did not reach the pre-specified threshold for significance.
The objective response rate (ORR) by BICR was 53% (nivolumab + chemotherapy), 35% (nivolumab + ipilimumab) and 20% (chemotherapy) in patients with PD-L1 ≥ 1% in tumor cells. The ORR in all randomized participants was 47%, 28%, and 27%, respectively.
The median duration of response for patients with PD-L1 esophageal SCC ≥ 1% was, respectively, 8.4; 11.8 and 5.7 months. The median for the entire randomized population, in turn, was 8.2; 11.1, and 7.1 months. No new safety signals were identified.
The researchers conclude that both nivolumab combined with chemotherapy and ipilimumab demonstrated superior OS versus chemotherapy alone, as well as sustained objective responses and acceptable safety in the population with advanced esophageal SCC, representing a potential new 1st-line treatment option.