Risk of hematological and gastrointestinal toxicities in patients with advanced neuroendocrine tumors treated with everolimus: A meta-analysis of phase 3 randomized controlled trials.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e16184-e16184
Author(s):  
Anita Sultan ◽  
Kyaw Zin Thein ◽  
Sriman Swarup ◽  
Somedeb Ball ◽  
Lukman Aderoju Tijani ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Neuroendocrine Tumors ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Phase 3 ◽  
Randomized Controlled

EPR19-74: Risk of Cabozantinib-Associated Gastrointestinal and Hepatic Toxicities in Patients With Metastatic Solid Tumors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

2019 ◽  
Vol 17 (3.5) ◽  
pp. EPR19-74
Author(s):  
Anita Sultan ◽  
Sriman Swarup ◽  
Francis Mogollon-Duffo ◽  
Ye Aung ◽  
Yin M. Myat ◽  
...  
Keyword(s):  
Systematic Review ◽  
Side Effects ◽  
Randomized Controlled Trials ◽  
Solid Tumors ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Growth Factor Signaling ◽  
High Grade ◽  
Phase 3 ◽  
Randomized Controlled

Background: Cabozantinib is an oral inhibitor of multiple tyrosine kinases and is used in treatment of multiple solid tumors, targeting several pathways such as vascular endothelial growth factor signaling pathway and proto-oncogenes MET, KIT, RET. These pathways are implicated in several tumor development and progression. We performed a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of gastrointestinal (GI) and hepatic toxicities among patients with metastatic solid tumors treated with cabozantinib. Methods: MEDLINE, EMBASE databases, and meeting abstracts from inception to September 2018 were queried. Phase 3 RCTs that mention GI and elevation of liver enzymes as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% CI. Random effects model was applied. Results: We included 4 phase 3 RCTs with a total of 2,703 patients with various solid tumors. The study arm used cabozantinib while the control arm utilized everolimus or placebo or prednisone. The relative risks of all-grade side effects were as follows: diarrhea, 2.495 (95% CI: 2.149–2.897, P<.0001); nausea, 1.849 (95% CI: 1.649–2.072; P<.0001); vomiting, 2.335 (95% CI: 1.724–3.163; P<.0001); stomatitis, 4.541 (95% CI: 0.908–22.696; P=.065); dysgeusia, 4.428 (95% CI: 2.67–7.343; P<.0001); elevated AST, 2.002 (95% CI: 1.331–3.011; P=.001); and elevated ALT, 1.988 (95% CI: 0.936–4.222; P=.074). The RR of high-grade side effects were as follows: diarrhea, 5.913 (95% CI: 3.655–9.566; P<.0001); nausea, 3.098 (95% CI: 1.266–7.581; P=.013); vomiting, 1.298 (95% CI: 0.395–4.265; P=.668); stomatitis, 3.837 (95% CI: 0.749–19.665; P=.107); dysgeusia, 1.522 (95% CI: 0.159–14.574; P=.716); elevated AST, 1.733 (95% CI: 1.101–2.728; P=.018); and elevated ALT, 2.489 (95% CI: 1.164–5.326; P=.019). Conclusion: The risk of developing all grades of diarrhea, nausea, elevated AST, and any-grade vomiting, dysgeusia as well as high-grade elevated ALT, was high in cabozantinib group. Timely recognition and providing good supportive care will enhance patients’ quality of life.

Relative risk of pneumonitis or interstitial lung disease (ILD) associated with the use of cyclin-dependent kinase inhibitors (CDK4/6i): A systematic review and meta-analysis of phase 3 randomized controlled trials.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1072-1072
Author(s):  
Nusrat Jahan ◽  
Sariya Wongsaengsak ◽  
Shabnam Rehman ◽  
Myrian Vinan-Vega ◽  
Lukman Aderoju Tijani ◽  
...  
Keyword(s):  
Systematic Review ◽  
Relative Risk ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Cyclin Dependent Kinase ◽  
Phase 3 ◽  
Randomized Controlled

1072 Background: All three currently approved cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) such as palbociclib, abemaciclib, and ribociclib are reported to cause significant pulmonary toxicities including fatal pneumonitis or interstitial lung disease (ILD). We conducted a systematic review and meta-analysis of phase 3 randomized controlled trials (RCTs) to determine the relative risk of pneumonitis or ILD associated with CDK4/6i. Methods: We conducted a systematic search using PRISMA guidelines in PubMed, EMBASE, American Society of Clinical Oncology and San Antonio Breast Cancer Symposium meeting abstracts from inception through Jan 30, 2021. Phase 3 RCTs using CDK4/6i in the intervention arm and reporting the number of events for pneumonitis or ILD were included in the analysis. The Cochran-Mantel-Haenszel method and random effects model were used to calculate the pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was tested by Cochran’s Q test and I2 value. Results: Five phase 3 RCTs — MONALEESA-3, MONALEESA-7, MONARCH plus, monarchE, and PALLAS — reported the number of events for any grade pneumonitis or ILD and were included in the final analysis. A total of 13,191 patients — 6,758 in the CDK4/6i arm and 6,433 in the control arm — were analyzed. Following regimens were used in CDK4/6i arms — MONALEESA-3: ribociclib + fulvestrant; MONALEESA-7: ribociclib + tamoxifen or a non-steroidal aromatase inhibitor + goserelin; MONARCH plus: in cohort A, abemaciclib + anastrozole or letrozole, and in cohort B, abemaciclib + fulvestrant; MonarchE: abemaciclib + standard-of-care adjuvant endocrine therapy (ET); PALLAS: Palbociclib + ET. In the control arms, all studies used placebo and respective endocrine therapies. Any grade pneumonitis or ILD was reported in 1.64% of patients in the CDK4/6i arm versus 0.68% of patients in the control arm. The pooled RR of any grade pneumonitis or ILD was 2.26, 95% CI: 1.60-3.19, P < 0.00001, I2 = 0%. Grade 3/4 pneumonitis or ILD was reported in 0.28% of patients in the CDK4/6i arm and 0.06% of patients in the control arm with pooled RR of 2.35, 95% CI: 0.37-15.08, P = 0.37, I2 = 34%. One grade 5 pneumonitis was reported in the monarchE. Conclusions: Cyclin-dependent kinase 4/6 inhibitors are associated with increased risk of any grade pneumonitis or ILD. Early detection and prompt initiation of appropriate interventions are vital to reduce the morbidity and mortality associated with CDK4/6i induced pneumonitis or ILD.

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