Frontline nivolumab plus chemo or ipilimumab maintains OS benefit in advanced ESCC

The combination of nivolumab (NIVO) with either chemotherapy (chemo) or ipilimumab (IPI) continues to confer overall survival (OS) benefit as first-line treatment for patients with advanced oesophageal squamous cell carcinoma (ESCC) compared with chemo alone, according to updated results of the CheckMate 648 trial presented at ASCO GI 2023.

With a longer follow-up of 29 months, the clinically meaningful improvement in OS with NIVO + chemo and NIVO + IPI vs chemo alone was maintained in both the PD-L1-positive population and all randomized patients, said lead author Dr Ken Kato from the National Cancer Center Hospital in Tokyo, Japan. [ASCO GI 2023, abstract 290]

In the PD-L1-positive population (patients with tumour-cell PD-L1 expression of ≥1 percent), median OS remained longer in the NIVO + chemo vs the chemo alone arm (15.0 vs. 9.1 months; hazard ratio [HR], 0.59). This effect was similarly seen in the comparison between NIVO + IPI and chemo alone (13.1 vs 9.1 months; HR, 0.62).

A similar trend was observed in the overall population for both NIVO + chemo vs chemo alone (median OS 12.8 vs 10.7 months; HR, 0.78) and NIVO + IPI vs chemo alone comparisons (median OS 12.7 vs 10.7 months; HR, 0.77).

At 24 months, OS rates were consistently higher among those treated with NIVO + chemo and NIVO + IPI compared with chemo alone in the PD-L1-positive population (31 percent and 34 percent, respectively, vs 12 percent). This trend was also seen in the overall population (29 percent and 32 percent vs 19 percent).

In the primary analysis, treatment with either NIVO + chemo or NIVO + IPI resulted in superior OS compared with chemo alone at a minimum follow-up of 13 months. [N Engl J Med 2022;386:449-462] These results led to the approval of both nivolumab-based combination regimens in May 2022 as first-line treatment for patients with advanced or metastatic ESCC. [www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-opdivo-combination-chemotherapy-and-opdivo-combination-yervoy-first-line-esophageal#main-content]

This global, open-label, phase III trial analysed 970 patients with previously untreated, unresectable advanced, recurrent, or metastatic ESCC. Participants were randomized 1:1:1 to receive NIVO 240 mg Q2W + chemo* Q4W (mean age 64 years), NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W (mean age 62 years), or chemo alone (mean age 64 years). The primary endpoints were OS and progression-free survival (PFS). These outcomes were assessed first in the PD-L1-positive cohort and then in the overall population.

As per blinded independent central review, longer PFS with NIVO + chemo vs chemo alone was maintained in the PD-L1-positive population (median 6.8 vs 4.4 months; HR, 0.67) and the overall population (median 5.8 vs 5.6 months; HR, 0.83).

"However, no PFS benefit was observed with NIVO + IPI vs chemo in either population, and this was consistent with that observed in the previous study,” said Kato.

NIVO + chemo outdid chemo alone in terms of objective response rates (ORR), both in the PD-L1-positive (53 percent vs 20 percent) and overall cohorts (47 percent vs 27 percent).

Between NIVO + IPI and chemo alone, ORR was higher with the former vs the latter in the PD-L1-positive population (35 percent vs 20 percent) but similar in the overall population (27 percent for both).

“Responses remained more durable with NIVO + chemo and NIVO + IPI vs chemo alone,” said Kato.

The current safety results in all treated patients were consistent with those previously reported, with no new safety signals identified with either combination regimen, Kato noted.

“Overall, NIVO + chemo and NIVO + IPI continued to demonstrate clinically meaningful survival benefit and durable responses vs chemo alone with longer follow-up in previously untreated patients with advanced ESCC,” said Kato.

“These results further support NIVO + chemo and NIVO + IPI as new first-line standard-of-care treatment regimens for patients with advanced ESCC,” he concluded.