Table 1 Characteristics of included studies in the systematic review and meta-analysis
Author, Publication Year, Country | Journal | Study design | No of patientsa | Study duration | Intervention and sample size | Study outcomes | Lung function inclusion criteria |
|---|---|---|---|---|---|---|---|
Bissler[11], 2008, USA | N Engl J Med | single-center prospective open-label phase 1–2 trial | 25 (6/12/7) | treatment 1 year, observation 1 year | Sirolimus (n = 25) | Renal AMLs, lung function, 6MWD, lung-cyst volume, AEs and neurologic assessment. | NA |
Davies [21], 2011, UK | Clin Cancer Res | multicenter prospective nonrandomized open label phase 2 trial | 16 (6/3/7) | treatment 2 years | Sirolimus (n = 16) | Renal AMLs, lung function, AEs and neurocognitive function. | NA |
McCormack [14], 2011, USA | N Engl J Med | multi-center, randomized, placebo-controlled study (MILES) | 89 (81/8/0) | treatment 1 year, obervation 1 year | sirolimus group (n = 46); placebo group (n = 43) | Lung function, 6MWD, VEGF-D levels and QOL scores and AEs. | FEV1 ≤ 70% |
Dabora [22], 2011,USA | PLoS ONE | multicenter, open label, single arm, phase 2 trail | 36 (0/21/15) | treatment 1 year | sirolimus (n = 36) | Renal AMLs, lung function, brain tumors and liver AMLs, skin lesions, VEGF-D levels, AEs. | NA |
Bissler [13],2013, USA | Lancet | multicenter randomized, double-blind, placebo-controlled, phase 3 study (EXIST-2) | 118 (5/24/89) | median everolimus 38 weeks (10–85 weeks) | everolimus group (n = 79); placebo group (n = 39) | AMLs, skin lesion, pulmonary function, VEGF-D levels, everolimus pharmacokinetics and AEs. | DLCO > 35% |
Budde [20], 2015, USA | Brit J Clin Pharmaco | multicenter randomized, double-blind, placebo-controlled, phase 3 study (EXIST-2) | 79 (2/20/57) | median everolimus 38 weeks (10–85 weeks) | everolimus(n = 79) | Associations between everolimus concentration and AMLs size, VEGF-D and other biomarker levels. | DLCO > 35% |
Goldberg [17], 2015, USA | Eur Respir J | multicenter, open-label, nonrandomised, phase 2 trial | 24 (19/5/0) | 26 weeks | everolimus, (n = 24) | AEs, everolimus pharmacokinetics, VEGF-D levels, lung function. | (30% ≤ FEV1 ≤ 80%) or (30% ≤ FEV1 ≤ 90% and DLCO < 80%) |
Takada [23], 2016, Japan | Annals ATS | mulcenter single arm, open-label trial (MLSTS) | 63b | 2-year study period | Sirolimus (n = 63) | AEs, lung function and QOL scores. | NA |
Bee [24], 2017, UK | Thorax | a prospective national cohort study, single arm | 47 (38/9/0) | 35.8 ± 18 months | Sirolimus (n = 47) | Lung function, AEs. | NA |