207 Background: Majority of breast cancers express the estrogen receptor or progesterone receptor. CDK4/6 signaling plays a role in endocrine therapy resistance and the benefit of inhibition of these pathways has been proven in studies. Yet the impact of these agents on hematological toxicities and febrile neutropenia is a considerable safety concern. Hence, we performed a systematic review and meta-analysis of randomized controlled trials (RCT). Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through June 2017 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 with 95% confidence interval (CI). Random effects model was applied. Results: Five RCTs (four phase 3 and one phase 2 studies) with a total of 2671 patients were eligible for analysis. The study arm used palbociclib-letrozole, palbociclib-fulvestrant, ribociclib-letrozole and abemaciclib-fulvestrant while the control arm utilized placebo in combination with letrozole or fulvestrant. The relative risks (RR) of all-grade side effects were as follows: anemia, 3.77 (95% CI: 2.47 – 5.75, p < 0.0001); thrombocytopenia, 9.69 (95% CI: 4.26 – 22.04, p < 0.0001); leukopenia, 11.68 (95% CI: 8.19–16.65; p < 0.0001); and neutropenia, 14.09 (95% CI: 10.73–18.49; p < 0.0001). The RR of high-grade adverse effects were as follows: anemia, 2.66 (95% CI: 1.29 – 5.45, p = 0.008); thrombocytopenia, 7.08 (95% CI: 1.95 – 25.74, p = 0.003); leukopenia, 33.58 (95% CI: 14.49–77.77; p < 0.0001); and neutropenia, 40.33 (95% CI: 19.34–84.10; p < 0.001). The pooled risk of neutropenic fever was statistically significant at 4.26 (95% CI: 1.11–16.26; p = 0.034). Conclusions: CDK 4/6 inhibitors based regimen significantly contributed to all hematological toxicities as well as febrile neutropenia. These toxicities affect patients’ quality of life, add financial burden and may lead to drug dosing inconsistencies.
The Impact of Massage Therapy on Function in Pain Populations—A Systematic Review and Meta-Analysis of Randomized Controlled Trials: Part II, Cancer Pain Populations
