Posts Tagged ‘parasites’

Parasites and Cancer

Larry H. Bernstein, MD, FCAP, Curator



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Can malignant transformation of parasite cells cause neoplasms in an immunosuppressed host? New research findings are summarized in a short video.

Teaching Topic
Nivolumab in Renal-Cell Carcinoma

R.J. Motzer and Others

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Each year, an estimated 338,000 new cases of renal-cell carcinoma are diagnosed worldwide, and approximately 30% of patients present with metastatic disease at the time of diagnosis. A number of targeted therapies have been approved for the treatment of advanced or metastatic renal-cell carcinoma. Although everolimus and other agents have changed the therapeutic landscape for this disease, these treatments are associated with limited overall survival after a given agent is no longer effective. Motzer et al. conducted a randomized, open-label, phase 3 study that compared nivolumab with everolimus in patients with advanced renal-cell carcinoma, who had previously received one or two cycles of antiangiogenic therapy.

Clinical Pearls
Clinical Pearl  Does nivolumab as compared to everolimus prolong survival in patients with renal-cell carcinoma who have previously received one or two cycles of antiangiogenic therapy?

In the study by Motzer et al., patients with advanced renal-cell carcinoma who had received previous antiangiogenic treatment had longer survival with nivolumab treatment than with everolimus treatment. The median overall survival was 25.0 months (95% confidence interval [CI], 21.8 to not estimable) in the nivolumab group and 19.6 months (95% CI, 17.6 to 23.1) in the everolimus group. Death occurred in 183 of the 410 patients (45%) randomly assigned to receive nivolumab and in 215 of the 411 patients (52%) randomly assigned to receive everolimus. The hazard ratio for death (from any cause) with nivolumab versus everolimus was 0.73 (98.5% CI, 0.57 to 0.93; P=0.002), which met the prespecified criterion for superiority.

Figure 1. Kaplan–Meier Curve for Overall Survival.

Clinical Pearl  Is nivolumab associated with a higher objective response rate than everolimus in previously treated patients?

In the study by Motzer et al., the objective response rate was higher with nivolumab than with everolimus (25% vs. 5%; odds ratio 5.98; 95% CI, 3.68 to 9.72; P<0.001). Partial responses were observed in 99 patients (24%) in the nivolumab group and in 20 patients (5%) in the everolimus group. Complete responses were observed in 4 patients (1%) in the nivolumab group and in 2 patients (<1%) in the everolimus group.

Morning Report Questions
Q. Is nivolumab associated with fewer treatment-related adverse events as compared to everolimus?

A. In the Motzer trial, treatment-related adverse events of any grade occurred in 319 of the 406 patients (79%) treated with nivolumab and in 349 of the 397 patients (88%) treated with everolimus. Grade 3 or 4 treatment-related adverse events occurred in 76 of the 406 patients (19%) treated with nivolumab and in 145 of the 397 patients (37%) treated with everolimus; the most common grade 3 or grade 4 event was fatigue (10 patients, 2%) with nivolumab and anemia (31 patients, 8%) with everolimus.

Table 2. Treatment-Related Adverse Events Reported in 10% or More of Treated Patients in Either Group.

Q. Was the benefit observed with nivolumab in the Motzer study linked to programmed death 1 ligand (PD-L1) expression in tumors?

A. A benefit was observed with nivolumab irrespective of PD-L1 expression. Nivolumab has been reported to be associated with pharmacodynamic changes in blood and tumor markers that are consistent with PD-1 inhibition. The study data corroborate previous studies that have indicated that higher levels of PD-L1 expression are associated with poorer survival in renal-cell carcinoma, but they do not support PD-L1 as a marker of treatment benefit in renal-cell carcinoma. The relationship between PD-L1 expression and outcomes after treatment with nivolumab appears to depend on tumor type and histologic class. An association between PD-L1 expression and improved outcomes with nivolumab treatment has been observed for metastatic melanoma and only some types of lung cancer.

Figure 3. Kaplan–Meier Curve for Overall Survival, According to Programmed Death 1 Ligand (PD-L1) Expression Level.


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