Research Spotlight

Cowey, C.L., Scherrer, E., Boyd, M., Aguilar, K.M., Beeks, A. and Krepler, C. (2021). “Pembrolizumab Utilization and Clinical Outcomes Among Patients With Advanced Melanoma in the US Community Oncology Setting: An Updated Analysis.” J Immunother Mar 17. [Epub ahead of print].

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Favorable outcomes have been observed with pembrolizumab among patients with advanced melanoma in clinical trials; however, limited evidence exists on the long-term efficacy in the real-world setting. This was an updated, retrospective observational study of adult patients with advanced (unresectable or metastatic) melanoma who initiated pembrolizumab (in any line of therapy) between January 1, 2014, and December 31, 2016, in The US Oncology Network and were followed through December 31, 2019 [median follow-up: 18.2 mo (range: 0.1-63.1 mo)]. Study data were sourced from electronic health records. Patient demographic, clinical, and treatment characteristics were assessed descriptively. Kaplan-Meier methods were used to evaluate overall survival (OS), time to treatment discontinuation, time to next treatment, physician-assessed time to tumor progression, and physician-assessed progression-free survival (rwPFS). Independent risk factors for OS and rwPFS were identified with multivariable Cox regression models. Of the 303 study-eligible patients, 119, 131, and 53 received pembrolizumab in the first-line, second-line, and third-line or beyond setting, respectively. Median OS across the study population was 29.3 months [95% confidence interval (CI): 20.3-49.7] and was the longest among those who received first-line pembrolizumab [42.8 mo (95% CI: 24.8-not reached)]. Median rwPFS across the study population was 5.1 months (95% CI: 4.0-7.6) and 8.1 months (95% CI: 4.6-14.4) among those who received first-line pembrolizumab. In the multivariable analyses for OS, increased age, worsening performance status, elevated lactate dehydrogenase, brain metastases, and pembrolizumab use in later lines were significantly associated a worse prognosis.

Cowey, C.L., Liu, F.X., Kim, R., Boyd, M., Fulcher, N., Krulewicz, S., Kasturi, V. and Bhanegaonkar, A. (2021). “Real-world clinical outcomes with first-line avelumab in locally advanced/metastatic Merkel cell carcinoma in the USA: SPEAR-Merkel.” Future Oncol Mar 12. [Epub ahead of print].

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Aim: To assess clinical outcomes in patients with locally advanced (la) or metastatic (m) Merkel cell carcinoma (MCC) initiating first-line (1L) avelumab in a USA community oncology setting. Materials & methods: Adults with laMCC or mMCC initiating 1L avelumab were identified from The US Oncology Network electronic health record database and chart review. Results: Median overall survival and progression-free survival were not reached in laMCC (n = 9) vs 20.2 and 10.0 months in mMCC (n = 19); response rates were similar (66.7% vs 63.2%). Conclusion: This is the first study to show clinical benefit in patients with laMCC receiving 1L avelumab in a US real-world setting. Response rates in patients with mMCC were consistent with pivotal trials.

Cogswell, R., Alam, A. and Joseph, S.M. (2021). “Letter by Cogswell et al Regarding Article, “Polypharmacy in Older Adults Hospitalized for Heart Failure”.” Circ Heart Fail 14(3): e008160.

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In the era of modern medicine, the older adult HF patient with reduced ejection fraction will be at least on a 4-drug regimen to help reduce morbidity and mortality, at the expense of polypharmacy. While the issues highlighted by Unlu and Denny et al demonstrate the need for further research in the domain of polypharmacy, our own community must standardize basic fundamental definitions and engage in research to inform our recommendations. Without this, the right polypharmacy may not be achieved. [No abstract; excerpt from article].

Chiruvolu, A., George, R., Stanzo, K.C., Kindla, C.M. and Desai, S. (2021). “Effects of Placental Transfusion on Late Preterm Infants Admitted to a Mother Baby Unit.” Am J Perinatol Mar 15. [Epub ahead of print].

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OBJECTIVE: Well-appearing late preterm infants admitted to a mother baby unit may benefit from either delayed cord clamping (DCC) or umbilical cord milking (UCM). However, there are concerns of adverse effects of increased blood volume such as polycythemia and hyperbilirubinemia. The purpose of this study is to examine the short-term effects of placental transfusion on late preterm infants born between 35(0/7) and 36(6/7) weeks of gestation. STUDY DESIGN:  In this pre- and postimplementation retrospective cohort study, we compared late preterm infants who received placental transfusion (161 infants, DCC/UCM group) during a 2-year period after guideline implementation (postimplementation period: August 1, 2017 to July 31, 2019) to infants who had immediate cord clamping (118 infants, ICC group) born during a 2-year period before implementation (preimplementation period: August 1, 2015 to July 31, 2017). RESULTS:  The mean hematocrit after birth was significantly higher in the DCC/UCM group. Fewer infants had a hematocrit <40% after birth in the DCC/UCM group compared with the ICC group. The incidence of hyperbilirubinemia needing phototherapy, neonatal intensive care unit (NICU) admissions, or readmissions to the hospital for phototherapy was similar between the groups. Fewer infants in the DCC/UCM group were admitted to the NICU primarily for respiratory distress. Symptomatic polycythemia did not occur in either group. Median hospital length of stay was 3 days for both groups. CONCLUSION:  Placental transfusion (DCC or UCM) in late preterm infants admitted to a mother baby unit was not associated with increased incidence of hyperbilirubinemia needing phototherapy, symptomatic polycythemia, NICU admissions, or readmissions to the hospital for phototherapy. KEY POINTS: · Placental transfusion was feasible in late preterm infants.. · Placental transfusion resulted in higher mean hematocrit after birth.. · Placental transfusion did not increase the need for phototherapy.. · Fewer admissions to the NICU for respiratory distress were noted in the placental transfusion group.

Butler, J., Anker, S.D., Filippatos, G., Khan, M.S., Ferreira, J.P., Pocock, S.J., Giannetti, N., Januzzi, J.L., Piña, I.L., Lam, C.S.P., Ponikowski, P., Sattar, N., Verma, S., Brueckmann, M., Jamal, W., Vedin, O., Peil, B., Zeller, C., Zannad, F. and Packer, M. (2021). “Empagliflozin and health-related quality of life outcomes in patients with heart failure with reduced ejection fraction: the EMPEROR-Reduced trial.” Eur Heart J 42(13): 1203-1212.

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AIMS: In this secondary analysis of the EMPEROR-Reduced trial, we sought to evaluate whether the benefits of empagliflozin varied by baseline health status and how empagliflozin impacted patient-reported outcomes in patients with heart failure with reduced ejection fraction. METHODS AND RESULTS: Health status was assessed by the Kansas City Cardiomyopathy Questionnaires-clinical summary score (KCCQ-CSS). The influence of baseline KCCQ-CSS (analyzed by tertiles) on the effect of empagliflozin on major outcomes was examined using Cox proportional hazards models. Responder analyses were performed to assess the odds of improvement and deterioration in KCCQ scores related to treatment with empagliflozin. Empagliflozin reduced the primary outcome of cardiovascular death or heart failure hospitalization regardless of baseline KCCQ-CSS tertiles [hazard ratio (HR) 0.83 (0.68-1.02), HR 0.74 (0.58-0.94), and HR 0.61 (0.46-0.82) for <62.5, 62.6-85.4, and ≥85.4 score tertiles, respectively; P-trend = 0.10]. Empagliflozin improved KCCQ-CSS, total symptom score, and overall summary score at 3, 8, and 12 months. More patients on empagliflozin had ≥5-point [odds ratio (OR) 1.20 (1.05-1.37)], 10-point [OR 1.26 (1.10-1.44)], and 15-point [OR 1.29 (1.12-1.48)] improvement and fewer had ≥5-point [OR 0.75 (0.64-0.87)] deterioration in KCCQ-CSS at 3 months. These benefits were sustained at 8 and 12 months and were similar for other KCCQ domains. CONCLUSION: Empagliflozin improved cardiovascular death or heart failure hospitalization risk across the range of baseline health status. Empagliflozin improved health status across various domains, and this benefit was sustained during long-term follow-up. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03057977.