Baseline ctDNA predicts survival in resected stage III–IV melanoma

Translational research on data from the CheckMate-915 trial demonstrated that baseline circulating tumour DNA (ctDNA) positivity in resected stage III–IV melanoma predicts poorer survival. Additionally, baseline ctDNA combined with IFNγ-status and tumour mutational burden improved the predictive value.

CtDNA is tumour DNA that can be detected in the bloodstream. Both, pre- and post-resection DNA has been associated with poor clinical outcomes [1].

Recently, results from the phase 3 CheckMate 915 trial (NCT03068455) showed that adjuvant dual immune checkpoint inhibition with nivolumab plus ipilimumab did not improve survival in patients with completely resected stage IIIC/D–IV melanoma compared with nivolumab alone [2]. Prof. Georgina Long (University of Sydney, Australia) presented the results of her current analysis of the predictive value of pre-treatment ctDNA for disease recurrence and survival in the adjuvant immunotherapy populations of the CheckMate 915 trial [3].

CheckMate-915 randomised 1,844 patients with resected stage IIIB/D–IV 1:1 to receive adjuvant nivolumab or nivolumab plus ipilimumab. Pre-treatment ctDNA was available from 1,127 patients (61% of intention-to-treat [ITT] population) who showed no difference in baseline characteristics and efficacy from the ITT population.  A trend towards a greater prevalence of ctDNA-positivity in higher stage III substages of melanoma was observed.

Additionally, an association was observed between ctDNA positivity and recurrence-free survival (HR 1.87) and distant metastases-free survival (HR 2.86) during follow-up (see Figure). This association was particularly strong during the first months of treatment. Of note, no significant interaction between baseline ctDNA status and the treatment arm was observed.

The predictive value of baseline ctDNA improved when it was combined with baseline IFNγ-status and tumour mutational burden. Again, the association of this combined marker with early recurrence was highest in the first months of treatment.

Based on these results, Prof. Long concluded that “pre-treatment ctDNA was associated with an increased risk of early recurrence across treatment arms. ctDNA is a useful biomarker for combined analyses predicting outcome for adjuvant melanoma.”

1. Lee B, et al. Ann Oncol 2019;30(9):1472–1478.
2. Long GV, et al. Cancer Res. 2021;81(13_Supplement):CT004.
3. Long GV, et al. Association of pre-treatment ctDNA with disease recurrence and clinical and translational factors in patients with stage IIIB-D/IV melanoma treated with adjuvant immunotherapy (CheckMate 915). Abstract 788O, ESMO Congress 2022, 09–13 September, Paris, France.

Figure: Association of baseline ctDNA with recurrence [3].

NIVO, nivolumab. IPI, ipilimumab.

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Posted on 16 November, 202216 November, 2022