RESUMO
Background: Both dabrafenib/trametinib (D/T) and anti-PD-1 monotherapy (PD-1) are approved adjuvant therapies for patients with stage III BRAF V600-mutant melanoma. However, there is still a lack of head-to-head comparative data. We aimed to describe efficacy and toxicity outcomes for these two standard therapies across melanoma centers. Methods: This multicenter, retrospective cohort study was conducted in 15 melanoma centers in Australia, China, Germany, Italy, Japan, UK, and US. We included adult patients with resected stage III BRAF V600-mutant melanoma who received either adjuvant D/T or PD-1 between Jul 2015 and Oct 2022. The primary endpoint was relapse-free survival (RFS). Secondary endpoints included overall survival (OS), recurrence pattern and toxicity. Findings: We included 598 patients with stage III BRAF V600-mutant melanoma who received either adjuvant D/T (n = 393 [66%]) or PD-1 (n = 205 [34%]) post definitive surgery between Jul 2015 and Oct 2022. At a median follow-up of 33 months (IQR 21-43), the median RFS was 51.0 months (95% CI 41.0-not reached [NR]) in the D/T group, significantly longer than PD-1 (44.8 months [95% CI 28.5-NR]) (univariate: HR 0.66, 95% CI 0.50-0.87, P = 0.003; multivariate: HR 0.58, 95% CI 0.39-0.86, P = 0.007), with comparable OS with PD-1 (multivariate, HR 0.90, 95% CI 0.48-1.70, P = 0.75). Similar findings were observed using a restricted-mean-survival-time model. Among those who experienced recurrence, the proportion of distant metastases was higher in the D/T cohort. D/T had a higher incidence of treatment modification due to adverse events (AEs) than PD-1, but fewer persistent AEs. Interpretation: In patients with stage III BRAF V600-mutant melanoma post definitive surgery, D/T yielded better RFS than PD-1, with higher transient but lower persistent toxicity, and comparable OS. D/T seems to provide a better outcome compared with PD-1, but a longer follow-up and ideally a large prospective trial are needed. Funding: Dr. Xue Bai was supported by the Beijing Hospitals Authority Youth Programme (QMS20211101) for her efforts devoted to this study. Dr. Keith T. Flaherty was funded by Adelson Medical Research Foundation for the efforts devoted to this study.
RESUMO
Patients with hepatitis C virus (HCV)-related cirrhosis treated with direct-acting antivirals (DAA) are still at risk of developing hepatocellular carcinoma (HCC). We investigated the accuracy of non-invasive scoring systems (NSS) for the prediction of de novo HCC development in patients treated with DAA on long-term follow-up (FU). We analyzed data from 575 consecutive patients with cirrhosis and no history of HCC who achieved a sustained virologic response (SVR) to DAA therapy. NSS (i.e., Forns index, APRI, FIB-4, ALBI, and aMAP) were calculated at 3 months after the end of therapy. Performance for de novo HCC prediction was evaluated in terms of area under the curve (AUC) and Harrell's C-index. During a median FU of 44.9 (27.8-58.6) months, 57 (9.9%) patients developed de novo HCC. All five NSS were associated with the risk of de novo HCC. At multivariate analysis, only the ALBI score resulted in being significantly and independently associated with de novo HCC development (adjusted hazard ratio = 4.91, 95% CI 2.91-8.28, p < 0.001). ALBI showed the highest diagnostic accuracy for the detection of de novo HCC at 1-, 3-, and 5-years of FU, with AUC values of 0.81 (95% CI 0.78-0.85), 0.71 (95% CI 0.66-0.75), and 0.68 (95% CI 0.59-0.76), respectively. Consistently, the best predictive performance assessed by Harrell's C-statistic was observed for ALBI (C-index = 0.70, 95% CI 0.62-0.77). ALBI score may represent a valuable and inexpensive tool for risk stratification and the personalization of an HCC surveillance strategy for patients with cirrhosis and previous history of HCV infection treated with DAA.