Significance of timing of therapeutic line on effectiveness of nivolumab for metastatic renal cell carcinoma

Objectives:This study aimed to clarify the significance of therapeutic timing on the effectiveness of nivolumab for treating metastatic renal cell carcinoma.Marterials and methods:Fifty-eight patients with metastatic renal cell carcinoma treated with nivolumab monotherapy were retrospectively studied.Patients who were treated with nivolumab as second-line therapy were included in the second-line group,while the others were included in the later-line group.The clinicopathological characteristics,effects of nivolumab,and prognoses of these groups were compared.Results:Twenty and thirty-eight patients were included in the second-line and later-line groups,respectively.There were no significant differences in the distribution of International Metastatic Renal Cell Carcinoma Database Consotium risk and other clinicopathological characteristics between the 2 groups.The proportion of patients whose objective best response was progressive disease in the second-line group was significantly lower than that in the later-line group(15%vs.50%,p=0.0090).The 50%progression-free survival with nivolumab in the second-line group was significantly better than that in the later-line group(not reached and 5 months,p=0.0018).Multivariate analysis showed that the second-line setting was an independent predictive factor for better progression-free survival(p=0.0028,hazard ratio=0.108).The 50%overall survival after starting nivolumab in the second-line and later-line groups was not reached and 27.8 months,respectively(p=0.2652).Conclusions:The therapeutic efficacy of nivolumab as second-line therapy is expected to be better than that of later therapy.

Molecular mechanisms of docetaxel resistance in prostate cancer

Docetaxel(DTX)chemotherapy offers excellent initial response and confers significant survival benefit in patients with castration-resistant prostate cancer(CRPC).However,the clinical utility of DTX is compromised when primary and acquired resistance are encountered.Therefore,a more thorough understanding of DTX resistance mechanisms may potentially improve survival in patients with CRPC.This review focuses on DTX and discusses its mechanisms of resistance.We outline the involvement of tubulin alterations,androgen receptor(AR)signaling/AR variants,ERG rearrangements,drug efflux/influx,cancer stem cells,centrosome clustering,and phosphoinositide 3-kinase/AKT signaling in mediating DTX resistance.Furthermore,potential biomarkers for DTX treatment and therapeutic strategies to circumvent DTX resistance are reviewed.