Efficacy of adjuvant therapy in patients with stage IIIA cutaneous melanoma
Menée à partir de données portant sur 628 patients atteints d'un mélanome cutané de stade IIIA (durée médiane de suivi : 2,6 ans), cette étude multicentrique rétrospective évalue l'efficacité, du point de vue de la survie sans récidive et de la survie sans métastase à distance, et la toxicité d'un traitement adjuvant (pembrolizumab, nivolumab ou dabrafénib avec tramétinib)
Background: Patients with resected American Joint Committee on Cancer 8th edition (AJCC v8) stage IIIA melanoma have been under-represented in clinical trials of adjuvant drug therapy. The benefit of adjuvant targeted therapy and immunotherapy in this population is unclear.
Patients and methods: In this multicenter, retrospective study, patients with stage IIIA melanoma (AJCC v8) who received adjuvant pembrolizumab or nivolumab (anti-PD1), BRAF/MEK-targeted therapy dabrafenib + trametinib (TT), or no adjuvant treatment (OBS) were included. Recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and toxicity rates were examined.
Results: A total of 628 patients from 34 centers across Australia, Europe and USA were identified – 256 in anti-PD1, 80 in TT and 292 in OBS. The median follow-up was 2.6 years (IQR, 1.6-3.4 years). The presence of some key poor prognostic variables was significantly higher in anti-PD1 compared to OBS.
The two-year RFS was 79.3% (95% CI, 74.1-84.8) for anti-PD1, 98.6% (95% CI, 96.0-100) for TT and 84.3% (95% CI, 79.9-89.0) for OBS. The two-year DMFS was 88.4% (95% CI, 84.3-92.8) in anti-PD1, 100% in TT and 91.1% (95% CI, 87.7-94.7) in OBS. Higher Breslow thickness and higher mitotic rate were associated with higher risk of recurrence in the anti-PD1 and OBS (P<0.05).
Rates of ≥ Grade 3 toxicities were 10.9% with anti-PD1 and 17.5% with TT; discontinuation due to toxicity occurred in 13.3% and 21.2%, respectively. Rates of unresolved toxicity at last follow-up were 26.9% in anti-PD1 and 12.5% in TT groups.
Conclusions: Stage IIIA melanoma has a modest risk of recurrence. Adjuvant anti-PD1 did not significantly improve RFS or DMFS compared to OBS alone. Adjuvant TT appears promising over anti-PD1 or OBS. Outcomes after adjuvant therapy in this population needs further study in larger datasets with longer follow up or prospective randomised trials.
Annals of Oncology , résumé 2024