Risk of gastrointestinal and hepatic toxicities in patients with hormone receptor-positive HER2-negative breast cancer treated with CDK 4/6 inhibitors: A systematic review and meta-analysis of randomized controlled trials.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18284-e18284
Author(s):  
Aung Tun ◽  
Kyaw Zin Thein ◽  
Yu Yu Thar ◽  
Asha Nayak ◽  
Elizabeth Guevara
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Adverse Effects ◽  
Meta Analysis ◽  
Controlled Trials ◽  
High Grade ◽  
Randomized Controlled ◽  
Hormone Receptor Positive ◽  
Relative Risks ◽  
Increased Risk

e18284 Background: CDK4/6 inhibitors are proven to be beneficial in patients with hormone receptor-positive HER2-negative breast cancer. Studies have suggested an increased risk of gastrointestinal (GI) events. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the risk of GI and hepatic toxicities. Methods: We systematically conducted a comprehensive literature search using MEDLINE and EMBASE databases through January 1, 2017. RCTs that mention GI symptoms and/or elevation of liver enzymes as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio with 95% confidence interval (CI). Results: Five RCTs with a total of 2021 patients were eligible for analysis. The study arm used palbociclib-letrozole, palbociclib-fulvestrant, and ribociclib-letrozole while the control arm used placebo with letrozole or fulvestrant. The relative risks of all-grade elevated AST was 2.6 (95% CI: 1.15–5.86; p = 0.02); all-grade elevated ALT: 2.82 (95% CI: 1.25–6.36; p = 0.01); all-grade stomatitis: 3.32 (95% CI: 2.09-5.28; p < 0000.1); all-grade nausea: 1.79 (95%CI: 1.25-2.58; p = 0.002); all-grade vomiting:1.55 (95% CI: 0.92-2.63; p = 0.10); and all-grade diarrhea: 1.59 (95% CI 1.28-1.98; p < 0.0001). The relative risks of high-grade elevated AST was 3.08 (95% CI: 1.42–6.67; p = 0.004); high-grade elevated ALT: 7.2 (95% CI: 2.81–18.43; p < 0.0001); high-grade stomatitis: 2.01 (95% CI: 0.22-18.02; p = 0.53); high-grade nausea: 0.76 (95%CI: 0.12-4.78; p = 0.77); high-grade vomiting: 0.88 (95% CI: 0.19-4.13; p = 0.87); and high-grade diarrhea: 1.23 (95% CI 0.52-2.92; p = 0.64). Conclusions: Our meta-analysis demonstrated that CDK 4/6 inhibitor-based regimens are associated with a higher risk of all-grade and high-grade elevated AST and ALT. Moreover, the regimen is associated with increased risk of all-grade stomatitis, nausea and diarrhea. Recognizing these adverse effects may help clinicians in delivering proper supportive care and thereby enhancing patients’ quality of life.

Risk of gastrointestinal and hepatic toxicities in patients with metastatic solid tumors treated with cabozantinib: A systematic review and meta-analysis of randomized controlled trials.

2017 ◽  
Vol 35 (31_suppl) ◽  
pp. 208-208
Author(s):  
Myo Zaw ◽  
Kyaw Zin Thein ◽  
Myat M. Han ◽  
Henry Palangdao Igid ◽  
Fred L. Hardwicke ◽  
...  
Keyword(s):  
Systematic Review ◽  
Side Effects ◽  
Randomized Controlled Trials ◽  
Solid Tumors ◽  
Tyrosine Kinases ◽  
Meta Analysis ◽  
Controlled Trials ◽  
High Grade ◽  
Randomized Controlled ◽  
Relative Risks

208 Background: The vascular endothelial growth factor (VEGF) signaling pathways and the proto-oncogenes MET, KIT and RET were implied in cancer development and progression. Cabozantinib is an oral inhibitor of multiple tyrosine kinases and hence employed in many solid tumors. 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 March 2017 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 with 95% confidence interval (CI). Random effects model was applied. Results: We included 3 RCTs with a total of 1999 patients treated with cabozantinib for various solid tumors. The study arm used cabozantinib while the control arm utilized everolimus, placebo or prednisone. The relative risks (RR) of all-grade side effects were as follows: diarrhea, 2.39 (95% CI: 2.01 – 2.85, P < 0.0001); nausea, 1.86 (95% CI: 1.64 – 2.10, P < 0.0001); vomiting, 2.53 (95% CI: 1.60 – 3.99, P < 0.0001); stomatitis, 4.08 (95% CI: 0.55 – 30.01, P = 0.16); dysgeusia, 4.23 (95% CI: 2.30 – 7.76, P < 0.0001); elevated AST, 2.04 (95% CI: 1.12 – 3.73, P = 0.02); and elevated ALT, 1.61 (95% CI: 0.67 – 3.88, P = 0.28). The RR of high-grade side effects were as follows: diarrhea, 5.93 (95% CI: 3.43 – 10.25, P < 0.0001); nausea, 4.05 (95% CI: 1.99 – 8.23, P < 0.0001); vomiting, 2.37 (95% CI: 1.26 – 4.44, P = 0.007); stomatitis, 3.36 (95% CI: 0.45 – 24.98, P = 0.23); dysgeusia, 1.52 (95% CI: 0.15 – 14.57, P = 0.71); elevated AST, 1.70 (95% CI: 0.72 – 4.01, P = 0.22); and elevated ALT, 3.00 (95% CI: 0.60 – 14.93, P = 0.17). Conclusions: The risk of developing all-grade and high-grade diarrhea, nausea and vomiting with cabozantinib is high. Moreover, it is associated with all-grade elevated AST and dysgeusia. Timely recognition and providing good supportive care will enhance patients’ quality of life.

Risk of infectious, hematological, and gastrointestinal side effects in patients treatedwith ibrutinib: A systematic review and meta-analysis of randomized controlled trials.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18265-e18265
Author(s):  
Myo Zaw ◽  
Kyaw Zin Thein ◽  
Aung Tun ◽  
Lukman Tijani ◽  
Elizabeth Guevara
Keyword(s):  
Systematic Review ◽  
Side Effects ◽  
Adverse Effects ◽  
Randomized Controlled Trials ◽  
Chemokine Receptors ◽  
Meta Analysis ◽  
Controlled Trials ◽  
High Grade ◽  
Randomized Controlled ◽  
Gastrointestinal Side Effects

e18265 Background: Bruton’s tyrosine kinase (BTK) is essential for signaling of B-cell and chemokine receptors. Ibrutinib targets BTK and has become frontier in many hematologic malignancies. We undertook systematic review and pooled analysis of randomized controlled trials (RCTs) to determine infectious, hematological and gastrointestinal risks associated with ibrutinib. Methods: We performed a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts through December 31, 2016. The RCTs that mention infectious, hematological and gastrointestinal side effects as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio with 95% confidence interval (CI). Results: Four RCTs with a total of 1505 patients were eligible for the analysis. Studies compared Ibrutinib (I) vs ofatumumab, I vs chlorambucil, I+ bendamustine (B)+ rituximab (R) vs placebo + B+ R and I vs temsirolimus were included in the analysis. The relative risks (RR) of all-grade side effects were as follows: infection, 1.34 (95% CI: 1.04 – 1.74; p = 0.02); pneumonia, 1.16 (95% CI: 0.82–1.66; p = 0.38); anemia, 0.77 (95% CI: 0.64 – 0.93; p = 0.007); neutropenia, 0.99 (95% CI: 0.87 – 1.14; p = 0.98); thrombocytopenia, 0.86 (95% CI: 0.71 – 1.04; p = 0.12); diarrhea, 1.74 (95% CI: 1.48 – 2.05; p < 0.0001); nausea, 0.94 (95% CI: 0.80 – 1.10; p = 0.45); and vomiting, 0.98 (95% CI 0.74 – 1.30; p = 0.93). The RR of high-grade adverse effects were as follows: febrile neutropenia, 1.32 (95% CI: 0.84 – 2.08; p = 0.21); infection, 1.20 (95% CI: 0.73 – 1.98; p = 0.45); pneumonia, 1.22 (95% CI: 0.76–1.95; p = 0.39); anemia, 0.48 (95% CI: 0.33 – 0.71; p < 0.0001); neutropenia, 0.99 (95% CI: 0.86 – 1.15; p = 0.94); thrombocytopenia, 0.61 (95% CI: 0.47 – 0.81; p = 0.001); diarrhea, 1.72 (95% CI: 0.88 – 3.34;p = 0.10); nausea, 2.56 (95% CI: 0.59 – 10.99; p = 0.20); and vomiting, 0.42 (95% CI 0.11 – 1.63; p = 0.21). Conclusions: Ibrutinib increased the risk of all-grade diarrhea and infection whereas the risks of all-grade anemia, high-grade anemia and thrombocytopenia were significantly lower in the study arm, favoring ibrutinib.

A systematic review and meta-analysis of randomized controlled trials to evaluate the risk of gastrointestinal and hepatic toxicities in patients with hormone receptor-positive HER2-negative metastatic breast cancer treated with CDK 4/6 inhibitors.

2017 ◽  
Vol 35 (31_suppl) ◽  
pp. 209-209
Author(s):  
Myo Zaw ◽  
Kyaw Zin Thein ◽  
Aung Tun ◽  
Myat M. Han ◽  
Yu Yu Thar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Side Effects ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Endocrine Resistance ◽  
Controlled Trials ◽  
High Grade ◽  
Randomized Controlled ◽  
Gi Symptoms

209 Background: Hormonal therapies function through CDK4/CDK6/E2F axis which is essential in luminal estrogen receptor positive breast cancer. Reactivation of these CDK4 and CDK6 kinases has been implicated in endocrine resistance. Many CDK 4/6 inhibitors were employed in studies with noteworthy safety concerns. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the risk of gastrointestinal (GI) and hepatic toxicities. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through June 2017 were queried. RCTs that mention GI symptoms 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 with 95% confidence interval (CI). Results: We included five RCTs with a total of 2671 patients treated with CDK 4/6 inhibitors. The study arm used palbociclib-letrozole, palbociclib-fulvestrant, ribociclib-letrozole and abemaciclib-fulvestrant while the control arm used placebo in combination with letrozole or fulvestrant. The relative risks (RR) of all-grade side effects were as follows: diarrhea, 1.72 (95% CI: 1.08 – 2.74, p = 0.02); stomatitis, 2.62 (95% CI: 1.43 – 4.79, p = 0.002); nausea, 1.59 (95% CI: 1.30–1.94; p < 0.0001); vomiting, 1.65 (95% CI: 1.06–2.56; p = 0.02); elevated AST, 2.30 (95% CI: 1.34–3.93; p = 0.002); and elevated ALT, 2.78 (95% CI: 1.90–4.08; p < 0.0001). The RR of high-grade side effects were as follows: diarrhea, 2.26 (95% CI: 0.39 – 13.09, p = 0.36); stomatitis, 2.14 (95% CI: 0.36 – 12.72, p = 0.40); nausea, 1.13 (95% CI: 0.28 –4.47; p = 0.86); vomiting, 0.79 (95% CI: 0.24 – 2.54; p = 0.69); elevated AST, 1.85 (95% CI: 0.74 – 4.64; p = 0.18); and elevated ALT, 4.33 (95% CI: 2.15 – 8.71; p < 0.0001). Conclusions: The risk of developing any-grade diarrhea, stomatitis, nausea, vomiting and elevated AST and ALT, was high in CDK 4/6 inhibitors based regimen. Moreover, it increased the risk of high-grade elevated ALT.

scholarly journals Poly(ADP-Ribose) Polymerase Inhibitors (PARPi) for Patients With Advanced Breast Cancer: a Meta-analysis of Randomized Controlled Trials

2020 ◽  
Author(s):  
YongCheng Su ◽  
XiaoGang Zheng
Keyword(s):  
Breast Cancer ◽  
Randomized Controlled Trials ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Parp Inhibitors ◽  
Cochrane Library ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Increased Risk ◽  
Grade 3

Abstract BACKGROUND: Poly(ADP–ribose) polymerase (PARP) inhibitors are new class of drugs that are currently being studied in several malignancies. However, datas about the efficacy and safety of the PARP inhibitors are limited. Therefore, we conducted a meta-analysis of randomized controlled trials (RCT) in patients with breast cancer.METHODS: Pubmed/Medline, Embase, Cochrane Library, and abstracts presented at the annual meeting of the American Society of Clinical Oncology (ASCO) were searched for articles published from 2000 to June 2018.Summary incidences and the RR, HR with 95% confidence intervals, were calculated by using a random-effects or fixed-effects model.RESULTS: The summary HR indicated PARPi was not associated with OS (HR=0.83, 95%CI 0.66–1.06, Z=1.49, P=0.14), while it could significantly improve PFS ande time to deterioration (TTD) of global health status/quality of life(GHS/QoL) as compared with traditional standard therapy, the HR was 0.60(95%CI 0.50-0.72; Z=5.52, P＜0.00001) and 0.4 (95%CI 0.29–0.54,z=5.80 ,p=0.000),respectively.The RR of grade 3 or more anemia ,fatigue and headache was 3.02 (95% CI, 0.69–13.17;p = 0.14,,I2=90%),0.77 (95%CI, 0.34–1.73;p=0.52,I2=7%) and 1.13 (95% CI,0.30–4.18;p=0.86,I2=0%),respectively.CONCLUSION: The findings of this meta-analysis showed that PARPi has no significant effect on OS, while it could significantly improve in PFS and TTD of GHS/QoL for patients with advanced or metastatic breast cancer.Furthermore,our findings also demonstrated that the PARPi treatment is connected with an increased risk of grade 3 or more anemia adverse events.

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