Search

Simple Summary: The aim of this study was to evaluate the predictive and prognostic value of the systemic immune-inflammation index (SII), which is based on peripheral blood platelet, neutrophil, and lymphocyte counts, in patients with metastatic renal cell carcinoma (mRCC) treated with ipilimumab plus nivolumab in the first-line setting. High SII score was an independent prognostic factor for worse progression-free survival and overall survival. The clinical benefit rate was higher for patients with a low SII index if compared to a high SII index. An increase in SII of >20% from baseline after 12 weeks of therapy was significantly associated with tumor progression at first imaging. The SII index is both prognostic and predictive and could refine decision making in patients treated with ipilimumab plus nivolumab. Background: The aim of this study was to evaluate the predictive and prognostic value of the systemic immune-inflammation index (SII) in patients with metastatic renal cell carcinoma (mRCC) treated with first-line ipilimumab plus nivolumab. Methods: This retrospective study included forty-nine mRCC patients treated with first-line ipilimumab plus nivolumab at the Department of Urology of the University of Tuebingen, Germany. SII was assessed before starting ipilimumab plus nivolumab therapy at the time of first imaging and at tumor progression. Optimal SII cut-off was stratified by ROC-analysis. Univariable and multivariable Cox regression analyses were used to evaluate the predictive and prognostic value of SII. Results: Optimal SII cut-off was 788. Twenty-nine/forty-nine patients had high SII (≥788) before initiation of ipilimumab plus nivolumab. High SII was an independent prognostic factor for worse progression-free (HR 2.70, p = 0.014) and overall survival (HR 10.53, p = 0.025). The clinical benefit rate was higher for patients with low SII if compared to high SII (80% vs. 32.1%). An increase in SII > 20% from baseline after twelve weeks of therapy was associated with progression at first imaging (p = 0.003). Conclusions: SII is both prognostic and predictive and could refine decision making in patients with unclear imaging on therapy with ipilimumab plus nivolumab. [ABSTRACT FROM AUTHOR]

Background A nivolumab monotherapy flat-dosing regimen of 480 mg every 4 weeks (Q4W) has been approved in several markets, including the United States, Canada, and European Union, as an alternative dosing regimen for several indications. Approvals of this Q4W regimen were based on population pharmacokinetic (PK) analyses, established flat exposure–response relationships, and clinical safety. The objective of this study was to compare the PK exposure of 480 mg Q4W with 3 mg/kg every 2 weeks (Q2W) and 240 mg Q2W using modeling and simulation, and to evaluate clinical safety of the Q4W regimen. Patients and methods Nivolumab PK exposure for the 480 mg Q4W schedule was simulated for 3817 patients across multiple tumor types and compared with those for the 3 mg/kg Q2W and 240 mg Q2W schedules. The safety profile of the Q4W schedule was assessed by analysis of clinical data from 61 patients who transitioned to nivolumab 480 mg Q4W from 3 mg/kg Q2W during four phase III clinical trials. Results Compared with 3 mg/kg Q2W, nivolumab 480 mg Q4W produced similar time-averaged concentration, approximately 16% lower trough concentration, and 45% higher peak concentration at steady state. The peak concentration for 480 mg Q4W was significantly lower than that of 10 mg/kg Q2W, a dose previously shown to have an acceptable tolerability and safety profile. Treatment-related adverse events (TRAEs) that started after transitioning from 3 mg/kg Q2W to 480 mg Q4W were reported in 14.8% of patients, with 1.6% of patients reporting grades 3–4 TRAEs. Pooled safety data for these patients are consistent with those for the 3 mg/kg Q2W schedules, and no new safety signals were identified. Conclusions The time-averaged steady-state exposure and safety profile of nivolumab 480 mg Q4W are consistent with that of 3 mg/kg Q2W across multiple tumor types. Nivolumab 480 mg Q4W represents a new dosing schedule option, and in addition to 240 mg Q2W, provides convenience and flexibility for patient care. Clinical trial numbers NCT01721772, NCT01668784, NCT01673867, NCT01642004 [ABSTRACT FROM AUTHOR]

Background Immuno-oncology has changed disease trajectory as well as prognosis. End-of-life(EOL) care and EOL discussion must be changed, but little is known about current situation in the real world. The aim of this study is to explore the quality of medical care in end stage lung cancer patients who had received immunotherapy (IT). Methods This is a retrospective chart review. We reviewed the data of lung cancer patients who had received IT and died in our hospital between January 2014 and December 2018. The coprimary outcome are the length of stay in hospital and at home within 30 days from death. Results We identified 77 patients who met the eligible criteria. Their characteristics were as follows: median age, 63(34-78) years, male/female, 53/24 cases, histology type were Ad/Sq/Others, 55/14/8 cases. Patient received 1(1-2) regimens and 2(1-41) cycles of IT. Nivolumab, 46 cases (59%), was the most used IT agent. Most of the patients (92%) lived with their family and about half (52%) of them lived in Tokyo. The median overall survival from the initial diagnosis was 474 (25-4889) days and the median duration between final administration of IT and death was 58 (2-626) days. Within 30 days of death, the number of emergency hospitalizations was 1 (0-2) times, the length of hospital stay was 18 (1-30) days, the length of staying at home was 12 (0-29) days. Eighteen cases (23%) were hospitalized for 30 days or more consecutively until the death. Although fifteen(83%) out of 18 cases hospitalized for palliative care, only 6 cases received palliative care team (PCT) intervention. The most common reasons for emergency hospitalization were dyspnea (33 cases, 42%). Forty-five patients (58%) had meetings with medical social workers(MSWs). Six cases were able to go back home with visiting medical care. Conclusion Percentage of intervention by PCT is low. And the intervention of MSWs is too late. To improve this situation, EOL discussion should be started earlier. [ABSTRACT FROM AUTHOR]