Search Results

You are looking at 1 - 2 of 2 items for

  • Author: Francis Mogollon-Duffo x
Clear All Modify Search
Full access

Sriman Swarup, Anita Sultan, Somedeb Ball, Francis Mogollon-Duffo, Nimesh Adhikari, Yin M. Myat, Myo H. Zaw, Catherine Jones and Kyaw Z. Thein

Background: Breast cancer is the most common cancer in women, and the majority of breast cancers express the estrogen receptor or progesterone receptor. Inhibition of CDK4/6 signaling pathway has shown survival benefit in advanced breast cancer by overcoming endocrine therapy resistance. Yet, there are considerable hematologic toxicities associated with CDK 4/6 inhibitors and hence, we performed a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk. Methods: MEDLINE, EMBASE databases, and meeting abstracts from inception through September 2018 were queried. RCTs that mention anemia, thrombocytopenia, leukopenia, neutropenia, and neutropenic fever as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR) and risk difference (RD) with 95% CI. Random effects model was applied. Results: 8 RCTs (7 phase III and 1 phase II studies) with a total of 4,557 patients were eligible. The study arms used palbociclib/ribociclib/abemaciclib with letrozole or anastrozole or fulvestrant or other hormonal agent while the control arms utilized placebo in combination with letrozole or anastrozole or fulvestrant or other hormonal agent. The RR of all-grade side effects were as follows: anemia, 3.494 (95% CI: 2.535–4.814; P<.0001); thrombocytopenia, 6.066 (95% CI: 3.055–12.046; P<.0001); leukopenia, 10.376(95% CI: 7.236–14.879; P<.0001); and neutropenia, 14.387 (95% CI: 10.877–19.031; P<.0001). The RR of high-grade adverse effects were as follows: anemia, 2.251 (95% CI: 1.393–3.637; P=.001); thrombocytopenia, 3.696 (95% CI: 1.417–9.642; P=.008); leukopenia, 22.083(95% CI: 12.126–40.217; P<.0001); neutropenia, 33.527(95% CI: 17.271–65.082; P<.001). Neutropenic fever was noted in 71 (3.73%) in CDK 4/6 inhibitors group vs 28 (2.18%) in control arm. The pooled RR was statistically significant at 12.056 (95% CI: 1. 352–3.127; P=.001) and RD was 0.014 (95% CI: −0.002–0.029; P=.078) Conclusion: CDK 4/6 inhibitors–based regimen significantly contributed to all hematologic toxicities as well as febrile neutropenia. The improved efficacy outcomes and manageable toxicities with CDK 4/6 inhibitors are observed with proper supportive care and close monitoring.

Full access

Anita Sultan, Sriman Swarup, Francis Mogollon-Duffo, Ye Aung, Yin M. Myat, Myo H. Zaw, Rachana Yendala, Nicholas D’Cunha and Kyaw Z. Thein

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.