ABSTRACT
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.
ABSTRACT
Selpercatinib and pralsetinib are RET inhibitors with substantial activity in advanced RET-rearranged NSCLC. We present a case of pralsetinib-related pneumonitis and leptomeningeal and brain metastases progression during treatment suspension for pneumonitis. During recovery, selpercatinib administration led to rapid neurologic response and complete intracranial response and allowed pneumonitis resolution. This case supports the safety of selpercatinib in patients with pneumonitis on pralsetinib and highlights its marked efficacy in leptomeningeal disease.
ABSTRACT
At the outset of the pandemic, SARS-CoV-2 was thought to present simply as persistent cough and fever. However, with time, the medical community noted a myriad of associated symptoms well-described in the literature. Medical complications were particularly common in elderly populations and many early publications described pneumonia, organ failure, acute respiratory distress syndrome, hypercoagulability/microthrombosis and superimposed bacterial/viral infections. There is, however, a lack of literature describing surgical complications of COVID-19 and as such little knowledge regarding safe surgical interventions. This case describes the presentation/management of a patient who developed COVID-19-associated necrotising pneumonia. Video-assisted thoracoscopy lobectomy was performed following CT demonstration of necrotising pneumonia. Pathological evaluation of the surgical resection specimen demonstrated the microarchitecture of a severely diseased COVID-19 lung-fibrosis. This case demonstrates the safe management of a necrotic lung using a minimal access approach in the context of COVID-19 infection.
