
A pooled analysis of six CheckMate studies in immune checkpoint inhibitor (ICI), specifically treatment with nivolumab plus ipilimumab (NIVO + IPI) versus NIVO monotherapy, aimed to describe the long-term overall survival in patients with ICI treatment-naïve unresectable/metastatic melanoma.
The studies for ICI-naïve unresectable/metastatic melanoma included CheckMate 003, 004, 066, 067, 069, and 511.
A study led by Georgina V. Long, PhD, MBBS, FRACP, and published in the Journal of Clinical Oncology analyzed data from 1,375 patients; 369 of 839 (44%) received NIVO + IPI and 168 of 536 (31%) patients received NIVO remained in follow-up. Nine (1%) and 22 (4%) patients, respectively, were still receiving treatment.
Baseline characteristics and efficacy data were pooled across the six studies. OS and melanoma-specific survival (MSS) rates at fixed time points were derived from Kaplan-Meier estimates while corresponding CIs were derived from the Greenwood formula for variance derivation and on long-long transformation applied on the survivor function.
In addition, OS and MSS Kaplan-Meier curves on the pooled data were generated; the Brookmeyer and Crowley method was used to calculate corresponding Cis; hazard ratio (HR) was based on an unstratified Cox proportional hazards model; and univariate analysis (UVA) and multivariate analysis (MVA) models were used to analyze clinically relevant baseline characteristics for OS separately and independently than from the Kaplan-Meier estimates and HRs. A classification and regression tree (CART) analysis was used to separate patients into different risk groups to determine potential predictors for survival.
Regarding NIVO + IPI, median OS results were as follows:
- CheckMate 004: not reached (NR) (95% CI, 56.3 to NR)
- CheckMate 069: 56.8 months (95% CI, 29.2-56.8)
- CheckMate 511: NR (95% CI, 48.6 to NR)
- CheckMate 067: 72.1 months (95% CI, 39.1 to NR)
Regarding NIVO monotherapy, median OS results were as follows:
- CheckMate 003: 20.3 months (95% CI, 7.2 to NR)
- CheckMate 066L 37.6 months (95% CI, 26.9-51.8)
- CheckMate 067: 36.9 months (95% CI, 29.1-59.2)
Of note, there was a clear convergence of OS for all the large studies in the survival curve overlay of the individual studies, thus strengthening results observed in the CheckMate 067 trial.
In addition, median follow-up for OS was 45.0 months for patients treated with NIVO + IPI and 35.8 months for patients treated with NIVO. OS was also longer with NIVO + IPI versus NIVO monotherapy (HR, 0.78; 95% CI, 0.67-0.91), with 6-year OS rates of 52% versus 41%, respectively.
Consistent benefit was observed in BRAF-mutant and BRAF-wild-type patients, as well as those with normal and elevated lactate dehydrogenase (LDH). Finally, clinical factors associated with decreased survival in both the MVA and CART analyses were LDH greater than the upper limit of normal with either treatment, age 65 years or older with NIVO + IPI, and the presence of liver metastases with NIVO monotherapy.
“In this large, pooled, nonrandomized retrospective analysis, we observed that NIVO + IPI provides longer OS than NIVO in patients with ICI treatment-naïve advanced melanoma,” the researchers concluded.