Mona Fouad

Risk of endocrine complications in cancer patients treated with immune check point inhibitors: a meta-analysis

BACKGROUND We performed a meta-analysis of the risk of endocrine adverse events associated with immune check point inhibitors. METHODS Eligible studies included randomized trials of cancer patients on immune checkpoint inhibitors; describing events of hypothyroidism, hyperthyroidism, hypophysitis and adrenal insufficiency. RESULTS A total of ten clinical trials were eligible for the meta-analysis. The relative risk of all-grade hypothyroidism, hyperthyroidism, hypophyisitis and adrenal insufficiency were 8.26 (95% CI: 4.67-14.62; p < 0.00001), 5.48 (95% CI: 1.33-22.53; p = 0.02); 22.03 (95% CI: 8.52-56.94; p < 0.00001), 3.87 (95% CI: 1.12-13.41; p = 0.03), respectively. CONCLUSION Our meta-analysis has demonstrated that the use of immune check point inhibitors is associated with an increased risk of hypothyroidism, hyperthyroidism, hypophysitis and adrenal insufficiency compared with control.

Risk of cardiovascular toxicities in patients with solid tumors treated with sunitinib, axitinib, cediranib or regorafenib: an updated systematic review and comparative meta-analysis.

BACKGROUND We performed a systematic review and comparative meta-analysis of cardiovascular toxicities associated with sunitinib, axitinib, cediranib or regorafenib; oral multi tyrosine kinase inhibitors. PATIENTS AND METHODS Eligible studies included randomized phase II and III trials of patients with solid tumors on sunitinib, axitinib, cediranib or regorafenib describing daily events of hypertension, left ventricular dysfunction, bleeding or thrombosis. RESULTS Patients treated with these four agents had a significantly increased risk of all-grade hypertension and bleeding. The RR of all-grade hypertension, bleeding, thrombosis and cardiac dysfunction were 2.78 (95% CI 2.03-3.81; p<0.00001), 1.93 (95% CI 1.41-2.64; p<0.00001), 0.85 (95% CI 0.60-1.19; p=0.50), 2.36 (95% CI 0.95-5.87; p=0.06), respectively. Exploratory subgroup analysis showed no effect of the agent used (sunitinib vs. axitinib vs. cediranib) in the risk of hypertension; while for bleeding, only the sunitinib subgroup RR was significant compared to axitinib or cediranib. CONCLUSIONS Our meta-analysis has demonstrated that sunitinib, axitinib, cediranib and regorafenib are associated with a higher risk of developing all grade and high grade hypertension compared with control. While for bleeding, only the sunitinib subgroup RR was significant compared to axitinib or cediranib. Clinicians should be aware of these risks and perform regular cardiovascular monitoring.

Risk of pneumonitis in cancer patients treated with immune checkpoint inhibitors: a meta-analysis

Background: A meta-analysis of the risk of pneumonitis associated with the use of immune checkpoint inhibitors in cancer patients has been conducted. Methods: Eligible publications included randomized trials of cancer patients on immune checkpoint inhibitors, describing events of all-grade and high-grade pneumonitis. Results: After exclusion of noneligible citations, a total of 11 clinical trials were eligible for the meta-analysis. The odds ratio was 3.96 [95% confidence interval (CI): 2.02–7.79; p < 0.0001] for all-grade pneumonitis and 2.87 (95% CI: 0.90–9.20; p = 0.08) for high-grade pneumonitis. Moreover, the odds ratio of all-grade pneumonitis with a nivolumab/ipilimumab combination versus ipilimumab monotherapy was 3.68 (95% CI: 1.59–8.50; p = 0.002) and, for high-grade pneumonitis, it was 1.86(95% CI: 0.36–9.53; p = 0.46). Subgroup analysis did not reveal a difference between lung cancer patients and other cancer patients in the risk of pneumonitis. Conclusions: Our analysis provided evidence that the use of immune checkpoint inhibitors is associated with an increased risk of all-grade pneumonitis compared with chemotherapy or placebo controls.

Risk of cutaneous toxicities in patients with solid tumors treated with immune checkpoint inhibitors: a meta-analysis.

BACKGROUND We performed a meta-analysis of the risk of cutaneous toxicities associated with immune checkpoint inhibitors. METHODS Eligible studies included randomized trials of patients with solid tumors on immune checkpoint inhibitors (ipilimumab, nivolumab, tremelimumab, pidlizumab and pembrolizumab); describing events of rash, vitiligo and pruritus. RESULTS A total of nine clinical trials were considered eligible for the meta-analysis. The relative risk of all-grade rash, vitiligo and pruritus was 4.06 (95% CI: 3.35-4.91; p < 0.0001), 16.3 (95% CI: 3.21-82.8; p = 0.0008) and 3.4 (95% CI: 2.24-5.16; p < 0.00001), respectively. CONCLUSION Our meta-analysis demonstrates that immune checkpoint inhibitors are associated with an increased risk of all grade skin rash, vitiligo and pruritus. Clinicians should perform regular clinical cutaneous monitoring.

Risk of gastrointestinal complications in cancer patients treated with immune checkpoint inhibitors: a meta-analysis

AIM We performed a meta-analysis of the risk of selected gastrointestinal toxicities associated with immune checkpoint inhibitors. PATIENTS & METHODS Eligible studies included randomized trials of patients with solid tumors on ipilimumab, nivolumab, pembrolizumab, tremelimumab, pidilizumab and atezolizumab, describing events of diarrhea, vomiting or colitis. RESULTS After exclusion of ineligible studies, a total of ten clinical trials were considered eligible for the meta-analysis. The relative risk of all-grade diarrhea, vomiting and colitis was 1.64 (95% CI: 1.19-2.26; p = 0.002), 0.72 (95% CI: 0.49-1.07; p = 0.1), 10.35 (95% CI: 5.78-18.53; p < 0.00001), respectively. CONCLUSION Our meta-analysis has demonstrated that immune checkpoint inhibitors are associated with a significantly increased risk of all grade and high-grade colitis.

Correlation of cetuximab-induced skin rash and outcomes of solid tumor patients treated with cetuximab: A systematic review and meta-analysis

BACKGROUND We performed a systematic review and meta-analysis of the correlation between cetuximab-induced skin rash and outcomes of solid tumor patients treated with cetuximab. PATIENTS AND METHODS Eligible studies included phase I, II and III trials of patients with solid tumors on cetuximab; describing events of skin rash and correlating skin rash with overall survival (OS), progression free survival (PFS) and/or overall response rate (ORR). RESULTS Our search strategy yielded 409 potentially relevant citations on CETUXIMAB from Pubmed/Medline, CENTRAL Cochrane registry and ASCO meeting library. After exclusion of ineligible studies, a total of 13 clinical trials were considered eligible for the meta-analysis, including 4 phase III trials, 8 phase II trials and one phase I trial. The occurrence of cetuximab-induced rash in patients was highly associated with improvements in PFS (HR=0.74; 95% CI: 0.63-0.86, P<0.0002), OS (HR=0.60; 95% CI: 0.47-0.76, P<0.0001), and ORR (RR=1.51, 95% CI: 1.26-1.81, P<0.00001), as compared to patients without rash. Exploratory subgroup analysis showed no effect of tumor types on the RR of ORR. CONCLUSIONS Our meta-analysis has demonstrated that cetuximab-induced rash is associated with a significantly improved OS, PFS and ORR. Cetuximab-induced skin rash may represent a prognostic factor in patients with advanced solid tumors.

Risk of cardiovascular toxicities in patients with solid tumors treated with sorafenib: an updated systematic review and meta-analysis

BACKGROUND We performed a systematic review and meta-analysis of cardiovascular toxicities associated with sorafenib. PATIENTS & METHODS Eligible studies included randomized Phase II and III trials of patients with solid tumors receiving daily sorafenib treatment that described the following events: hypertension, bleeding, venous thromboembolism, left ventricular dysfunction myocardial ischemia and cerebrovascular events. RESULTS A total of 18 randomized clinical trials were considered eligible for the meta-analysis. Patients treated with sorafenib had a significantly increased risk of hypertension (relative risk [RR]: 2.93; 95% CI: 1.52-5.66), bleeding (RR: 2.42; 95% CI: 1.63-3.62) and left ventricular dysfunction (RR: 9.38; 95% CI: 1.24-71.22). The risk for venous thromboembolism, myocardial ischemia and cerebrovascular events was nonsignificant. Subgroup analyses showed that tumor type and treatment regimen had no effect on the RR of cardiovascular toxicities. CONCLUSION Our meta-analysis demonstrated that sorafenib is associated with a higher risk of developing all grade hypertension and bleeding compared with controls.

Risk of thyroid dysfunction in patients with solid tumors treated with VEGF receptor tyrosine kinase inhibitors: a critical literature review and meta analysis

We performed a systematic review and meta-analysis of thyroid function abnormalities associated with seven vascular endothelial growth factor receptor (VEGFR) targeted tyrosine kinase inhibitors (sorafenib, sunitinib, axitinib, cediranib, pazopanib, regorafenib and vandetanib). Eligible studies included randomized Phase II and III trials of patients with solid tumors on sorafenib OR sunitinib OR axitinib OR cediranib OR pazopanib OR regorafenib OR vandetanib; describing events of hypothyroidism or hyperthyroidism. Our search strategy yielded 195 potentially relevant citations on the seven agents from Pubmed/Medline, CENTRAL Cochrane registry and ASCO meeting library. After exclusion of ineligible studies, a total of 12 clinical trials were considered eligible for the meta-analysis, including six sunitinib studies, four cediranib studies and two axitinib studies. Patients treated with these agents had a significantly increased risk of all-grade hypothyroidism and the relative risk (RR) of all-grade hypothyroidism was 3.59 (95% CI = 2.40–5.38, p ≤ 0.0001). Exploratory subgroup analysis showed no effect of tumor types or agent used on the RR of hypothyroidism. Our meta-analysis has demonstrated that these three agents are associated with a significantly increased risk of all-grade hypothyroidism; with no difference – on subgroup analysis – between sunitinib and cediranib. Clinicians should be aware of these risks and perform regular thyroid function monitoring.

Risk of mucocutaneous toxicities in patients with solid tumors treated with sorafenib: an updated systematic review and meta-analysis

We performed a systematic review and meta-analysis of mucocutaneous toxicities associated with sorafenib, an oral multi tyrosine kinase inhibitor. Eligible studies included randomized Phase II and III trials of patients with solid tumors on sorafenib daily describing events of hand foot skin reaction, skin rash, alopecia, stomatitis or pruritis. Patients treated with sorafenib had a significantly increased risk of all-grade mucocutaneous toxicities. The RR of all-grade hand foot skin reaction, skin rash, alopecia, stomatitis and pruritis were 4.33 (95% CI: 3.06–6.14), 2.67 (95% CI: 1.86–3.83), 3.93 (95% CI: 2.07–7.45), 2.9 (95% CI: 2.26–3.73), 2.29 (95% CI: 1.87–3.03); respectively. Exploratory subgroup analysis showed no effect of tumor types or treatment regimen (monotherapy versus combination) on the RR of mucocutaneous toxicities. Our meta-analysis has demonstrated that sorafenib is associated with a higher risk of developing all grade mucocutaneous toxicities compared with control.

Risk of mucocutaneous toxicities in patients with solid tumors treated with sunitinib: a critical review and meta analysis

Introduction: we performed a systematic review and meta-analysis of mucocutaneous toxicities associatedwith sunitinib, an oral multi-tyrosine kinase inhibitor. Methods: eligible studies included randomized Phase II and III trials of patients with solid tumors on sunitinib daily, describing events of hand–foot syndrome, skin rash, stomatitis, and skin and hair discoloration. Results: the relative risk (RR) of all-grade hand–foot skin reaction, skin rash, stomatitis, skin and hair discoloration were 2.12 (95% CI: 1.28–3.51; p < 0.004), 1.33 (95% CI: 1.15–1.54; p < 0.0002), 1.88 (95% CI: 1.36–2.59; p = 0.0001), 16.6 (95% CI: 4.18–64.94 p < 0.003), 4.42 (95% CI: 0.8–24.5; p < 0.09); respectively. Conclusions: our meta-analysis has demonstrated that sunitinib is associated with a higher risk of developing all-grade hand–foot skin reaction, skin rash, stomatitis and skin discoloration compared with control. Clinicians should be aware of these risks and perform regular clinical monitoring.