RESUMO
AIM: Sirolimus, a mammalian target of rapamycin inhibitor, inhibits cell growth and proliferation by controlling ribosome biogenesis and protein synthesis in vascular anomalies and cancers. However, most sirolimus studies on vascular anomalies were conducted in the pediatric population, with limited data in adults. In this study, we assessed the effectiveness and safety of sirolimus in adult patients with vascular malformation, a subtype of vascular anomaly. METHODS: We conducted a retrospective analysis of adult vascular malformation patients aged over 16, treated at Hacettepe University Cancer Institute from January 2013 to September 2022. Patient demographics and clinical characteristics were recorded. The primary outcome was the efficacy of sirolimus evaluated by response and disease control rates. The disease control rate was defined as the cumulative percentage of complete or partial responses, along with stable disease. The secondary endpoint was toxicity and safety. RESULTS: 38 patients with a median age of 21 (IQR: 18-33) were recruited. Prior to sirolimus treatment, 57.9% of patients had undergone other therapeutic interventions, predominantly sclerotherapy and surgery. The median follow-up time during sirolimus treatment was 18.5 (IQR: 11.3-74.5) months. The disease control rate was 92.1% (35/38). Head-neck localization was associated with better response rates (p = .001). Sirolimus was generally well tolerated and grade 1 or 2 oral mucositis (n = 4) and skin rash (n = 3) were the most common side effects. CONCLUSION: In this study, we found sirolimus was efficacious and well tolerated in adult patients with vascular malformation.
RESUMO
Human epidermal growth factor receptor 2 (HER2)-targeting therapies have become crucial in the management of HER2-positive breast cancer. Trastuzumab emtansine (T-DM1) is a microtubule inhibitor and HER2-targeted antibody conjugate. T-DM1 resistance is most likely influenced by factors involved in the biological mechanisms of T-DM1 action. This study aimed to examine the efficacy of statins, which influence HER-2-based therapies via the caveolin-1 (CAV-1) protein, in female breast cancer patients receiving T-DM1. Our study included 105 patients with HER2-positive metastatic breast cancer treated with T-DM1. The progression-free survival (PFS) and overall survival (OS) of patients who received statins concurrently with T-DM1 versus those who did not were compared. During the median 39.5 (95% confidence interval [CI]: 35.6-43.5) months of follow-up, 16 (15.2%) patients received statins, and 89 (84.8%) patients did not. Median OS was significantly higher in patients using statins than in patients not using statins (58.8 vs 26.5 months, P = .016). The association between statin use and PFS did not reach statistical significance (34.7 vs 9.9 months, P = .159). Multivariate Cox regression analysis showed that better performance status (hormone receptor [HR]: 0.30, 95% CI: 0.13-0.71, P = .006), use of trastuzumab plus pertuzumab prior to T-DM1 (HR: 0.37, 95% CI: 0.18-0.76, P = .007) and use of statins with T-DM1 (HR: 0.29, 95% CI: 0.12-0.70, P = .006) were independent factors that prolong OS duration. Our study showed that T-DM1 is more effective at treating HER2-positive breast cancer in people who receive statins concurrently with T-DM1 than those who do not.
