Hesham Elhalawani

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 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.

Risk of fatal pulmonary events in patients with advanced non-small-cell lung cancer treated with EGF receptor tyrosine kinase inhibitors: a comparative meta-analysis

We performed a meta-analysis of fatal pulmonary events associated with erlotinib, gefitinib or afatinib in patients with non-small-cell lung cancer (NSCLC). Eligible studies included randomized trials of patients with NSCLC on the three drugs describing events of high-grade pulmonary events. The relative risk of high-grade interstitial lung disease, pneumonitis, pneumonia, pulmonary embolism and hemoptysis were 4.18 (95% CI: 2.49-7.01; p < 0.00001), 1.94 (95% CI: 0.93-4.06; p = 0.08), 1.28 (95% CI: 0.92-1.77; p = 0.14), 1.6 (95% CI: 0.81-3.18 p = 0.17), 1.00 (95% CI: 0.14-7.08 p = 0.35), respectively. Our meta-analysis has demonstrated that erlotinib, gefitinib and afatinib are associated with an increased risk of high-grade interstitial lung disease in patients with NSCLC.

Risk of elevated transaminases in non-small cell lung cancer (NSCLC) patients treated with erlotinib, gefitinib and afatinib: a meta-analysis

ABSTRACT This meta-analysis has been conducted to determine the risk of elevated transaminases associated with the use of erlotinib, gefitinib and afatinib in patients with non-small cell lung cancer (NSCLC). Studies eligible for our analysis included randomized phase II and III trials of patients with NSCLC on the three agents which describe events of elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Initial database search revealed 300 relevant citations. After excluding non-eligible studies, 24 trials were considered eligible for the analysis. The relative risk (RR) of all-grade elevated ALT and AST was 1.82 (95% CI: 1.42–2.34; p < 0.00001) and 2.09 (95% CI: 1.54–2.83; p < 0.00001) respectively; while for high-grade elevated ALT and AST, it was 9.23 (95% CI: 5.06–16.85; p < 0.00001) and 1.78 (95% CI: 0.5–6.26; p = 0.37), respectively. Our meta-analysis has shown that there is an overall elevated risk of elevated transaminases with the use of these agents.

Critical evaluation of ramucirumab in the treatment of advanced gastric and gastroesophageal cancers

Gastric (GC) and gastroesophageal junction (GEJ) cancers are two global health problems with a relatively high mortality, particularly in the advanced stage. Inhibition of angiogenesis is now contemplated as a classic treatment preference for myriad tumor types encompassing renal cell carcinoma, non-small cell lung cancer, colorectal cancer, glioblastoma, and ovarian cancer, among others. Bevacizumab and ramucirumab have been widely investigated in GC and GEJ cancer, with some controversy about their therapeutic role. Ramucirumab is a monoclonal antibody for vascular endothelial growth factor receptor-2, with demonstrated activity both as a monotherapy and as a part of combination strategy in the management of advanced GC/GEJ cancer. In this review article, we present a critical evaluation of the preclinical and clinical data underlying the use of this drug in this indication. Moreover, we provide a spotlight on the future perspectives in systemic therapy for advanced GC/GEJ cancer.

Risk of selected dermatological toxicities in cancer patients treated with MEK inhibitors: a comparative systematic review and meta-analysis

BACKGROUND This meta-analysis was conducted aiming at assessing the risk of selected dermatological toxicities associated with MEK inhibitors. METHODS We considered relevant prospective randomized Phase II and III trials of cancer patients on the three MEK inhibitors (trametinib, selumetinib and cobimetinib), describing events of skin rash and acneiform dermatitis, as eligible for inclusion. RESULTS After exclusion of ineligible studies, a total of 14 clinical trials were considered eligible for the meta-analysis. The relative risk of all-grade skin rash and acneiform dermatitis was 1.71 (95% CI: 1.07-2.72; p = 0.02) and 6.55 (95% CI: 3.42-12.56; p < 0.00001), correspondingly; while the relative risk of high-grade skin rash and acneiform dermatitis was 2.64 (95% CI: 1.42-4.91; p = 0.002) and 8.44 (95% CI: 2.39-29.81; p = 0.0009), respectively. CONCLUSION Our meta-analysis has demonstrated that MEK inhibitor-based treatment is associated with an increased risk of all-grade and high-grade skin rash and acneiform dermatitis compared with control.

Risk of oral and gastrointestinal mucosal injury in patients with solid tumors treated with ramucirumab: a systematic review and meta-analysis

Background: We performed a systematic review and meta-analysis of the risk of oral and gastrointestinal (GI) mucosal injury associated with ramucirumab. Patients and methods: Eligible studies included randomized Phase II and III trials of patients with solid tumors on ramucirumab: describing events of stomatitis, diarrhea, GI perforation and GI hemorrhage. Results: Our search strategy yielded 167 potentially relevant citations from Pubmed/Medline, CENTRAL Cochrane registry, European society of medical oncology meeting abstracts and American Society of Clinical Oncology meeting library. After exclusion of ineligible studies, a total of 11 clinical trials were considered eligible for the meta-analysis. The RR of all-grade stomatitis, diarrhea, GI perforation and GI hemorrhage were 1.62 (95% CI 1.31 – 2.00; p < 0.00001), 1.15 (95% CI 1.07 – 1.24; p < 0.0001), 3.29 (95% CI 1.54 – 7.04; p = 0.002) and 1.92 (95% CI 1.03 – 3.57; p = 0.04), respectively. The RR of high-grade stomatitis, diarrhea, GI perforation and GI hemorrhage were 2.72 (95% CI 1.76 – 4.19; p < 0.00001), 1.28 (95% CI 0.96 – 1.71; p = 0.09), 3.37 (95% CI 1.51 – 7.54; p = 0.03) and 1.26 (95% CI 0.79 – 2.01; p = 0.34), respectively. Conclusions: Our meta-analysis has demonstrated that ramucirumab-based combination treatment is associated with an increased risk of high-grade stomatitis and GI perforation compared to control treatment.

Adjuvant systemic treatment for elderly breast cancer patients; addressing safety concerns

Introduction: The issue of systemic treatment for early breast cancer in the elderly has always been challenging and in spite of the clear evidence of the potential benefits of adjuvant treatment in older women, they are usually undertreated with the potential consequence of worse outcomes. Areas covered: This article will review the evidence surrounding the various systemic options in the treatment armamentarium of early-stage breast cancer in elderly patients. The risks and benefits, with particular attention to a number of newly introduced targeted agents, along with the potential role of incorporating a combined geriatric/oncologic assessment as a routine part of the management of elderly patients with breast cancer are considered. Expert opinion: Administration of available options for (neo)adjuvant endocrine, chemo, as well as targeted therapeutics in fit elderly patients is feasible and tolerable; however, a routine input from geriatric medicine and psycho-oncology experts as well as the training of specialized oncology staff with special interest in geriatric oncology are believed to improve the outcome of elderly patients.

Proteinuria in Patients with Solid Tumors Treated with Ramucirumab: A Systematic Review and Meta-Analysis.

Background: We performed a systematic review and meta-analysis of the risk of proteinuria associated with ramucirumab. Methods: Eligible studies included randomized phase II and III trials of patients with solid tumors on ramucirumab, describing events of all-grade and high-grade proteinuria. Results: Our search strategy yielded 170 potentially relevant citations from PubMed/Medline, CENTRAL Cochrane database, ASCO and ESMO meeting libraries. After exclusion of ineligible studies, a total of 11 clinical trials were considered eligible for the meta-analysis. The relative risk (RR) of all-grade proteinuria was 3.31 (95% CI 2.48-4.42; p < 0.00001). Moreover, the RR of high-grade proteinuria was 5.28 (95% CI 2.32-12.01; p < 0.0001). Conclusions: Our meta-analysis has demonstrated that ramucirumab use is associated with an increased risk of all-grade and high-grade proteinuria. Early detection strategies should be employed in those patients to prevent the progression to more sinister renal disease.