Prognostic and predictive biomarkers in patients with resected stage IIB/C melanoma

Adjuvant treatment with nivolumab decreases the risk of recurrence in patients with stage II melanoma. A biomarker analysis of the CheckMate76K data showed that baseline tumour mutation burden and IFNγ signal are associated with a higher benefit of nivolumab.

Patients with resected stage IIA/B/C melanoma face a 5-year risk of recurrence of 24–43% [1]. The phase 3 CheckMate76K study (NCT04099251) evaluated the efficacy and safety of adjuvant nivolumab for 12 months in patients with resected stage IIB/C melanoma. Recently published results showed that adjuvant nivolumab significantly increased recurrence-free survival (RFS; HR 0.42; P<0.0001) [2].

In addition, Prof. Georgina Long (University of Sydney, Australia) and colleagues performed an exploratory biomarker analysis to determine patient subgroups that have a high risk of recurrence (prognostic biomarkers) and to understand the benefit of adjuvant nivolumab treatment in biomarker-defined subgroups of patients (predictive biomarkers) [3].

In CheckMate76K, 790 patients were randomised 2:1 to adjuvant nivolumab or placebo. Baseline biomarkers were obtained from serum (i.e. CRP) and primary tumour biopsy (i.e. IFNγ signal, tumour mutation burden [TMB], BRAF^v600 status, percentage CD8 T cells, PD-L1 expression, and tumour mitotic rate [TMR]). Analyses were performed within each treatment arm and comparing nivolumab with placebo treatment.

Within the nivolumab arm, a higher IFNγ signal, TMB, and CD8 T cell count, and lower serum CRP were associated with improved RFS. Within the placebo arm, none of the biomarkers tested was prognostic for RFS.

In addition, a higher IFNγ signal, TMB, CD8 T cell count, and lower serum CRP were predictive of the benefit of nivolumab versus placebo. For example, patients with a high IFNγ signal had more benefit from nivolumab versus placebo (HR 0.29) compared with patients with a low IFNγ signal (HR 0.44).

In a multivariate analysis, tumour stage and CRP level at baseline proved to be the strongest independent prognostic biomarkers in this population. TMB and IFNγ signalling were the strongest independent predictive biomarkers (see Figure).

Figure: Multivariate analysis of biomarkers with prognostic and predictive value [3]



CRP, c-reactive protein; NIVO, nivolumab; PBO, placebo; RFS, recurrence-free survival; TMB, tumour mutation burden.

Based on these results, Prof. Long concluded that “among all the biomarkers tested, TMB and IFNγ signalling had the largest independent effect of the relative benefit of nivolumab over placebo.”

1. Garbe C, et al. J Clin Oncol.2022;32:3741–3749.
2. Long GV, et al. SMR Annual Meeting 2022, 17–20 October, Edinburgh, Scotland.
3. Long GV, et al. Association of biomarkers with efficacy of adjuvant nivolumab vs placebo in patients with resected stage IIB/C melanoma (CA209-76K). Abstract 9504, ASCO Annual Meeting 2023, 2–6 June, Chicago, USA.

 

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Posted on 2 August 20232 August 2023