RM-041 Risk of selected gastrointestinal toxicities in cancer patients treated with Pazopanib: a systematic review and meta-analysis

Abstract

:Introduction: Targeting tumor angiogenesis has emerged as the state of the art strategy in treating different types of solid tumors. Tyrosine kinase inhibitors (TKIs) are anti-angiogenic agents targeting vascular endothelial growth factor receptors (VEGFR). Pazopanib is one of the agents in this class, has been approved recently in metastatic soft tissue sarcoma and metastatic renal cell carcinoma.We constructed this meta-analysis of gastrointestinal adverse events associated with Pazopanib use in solid tumors patients. Targeting tumor angiogenesis has emerged as the state of the art strategy in treating different types of solid tumors. Tyrosine kinase inhibitors (TKIs) are anti-angiogenic agents targeting vascular endothelial growth factor receptors (VEGFR) Pazopanib is one of the agents in this class, has been approved recently in metastatic soft tissue sarcoma and metastatic renal cell carcinoma.We constructed this meta-analysis of gastrointestinal adverse events associated with Pazopanib use in solid tumors patients. Methods: Eligible studies included randomized phase 2 and 3 trials of patients receiving Pazopanib. They described adverse events of nausea, vomiting, diarrhea, abdominal pain, loss of appetite, anorexia and loss of weight. Our search strategy yielded 244 potentially eligible citations from PUBMED/MEDLINE, Google scholar, clinical trials.gov, ASCO and ESMO meetings library. Results: After excluding ineligible studies, a total of 15 RCTs were included in this analysis distributed as six phase II trials and eight phase III trials, with a total of 4592 patients.The most commonly documented GI AE was diarrhea with an incidence rate 30% to 67%. The RR of all-grade nausea, vomiting, diarrhea, abdominal pain, decreased appetite, anorexia and decreased weight were 1.4 (95% CI 1.23, 1.61;p < 0.00001), 1.63 (95% CI 1.36, 1.96; p < 0.00001), 3.55 (95% CI 3.05, 4.13; p < 0.00001), 1.57 (95% CI 1.28, 1.92; p < 0.0001), 1.35 (95% CI 1.01, 1.81; p < 0.04), 1.96 (95% CI 1.49, 2.58; p < 0.00001) and 3.12 (95% CI 2.34, 4.16; p < 0.00001[o1]); respectively. On the other hand, the RR of high-grade diarrhea, abdominal pain and anorexia were 3.28 (95% CI 2.16, 4.99; p < 0.00001), 2.1 (95% CI 1.05, 4.19; p < 0.04) and 4.67 (95% CI 1.5, 14.48; p < 0.008); respectively. Conclusion: In this meta-analysis, it has become evident that Pazopanib treatment is associated with increased risk of all grade and high grade diarrhea, anorexia and abdominal pain, among others. Future studies should correlate between such toxicities and interruptions of treatment as well as its impact on clinical outcome.