Nivolumab in patients with metastatic renal cell carcinoma and chronic hepatitis C virus infection.

BACKGROUND: Hepatitis C virus (HCV) interferes with activation of innate and adaptive immune responses. Theoretically, the efficacy and toxicity of immune checkpoint inhibitors in cancer patients infected with HCV may differ. Nevertheless, HCV was an exclusion criterion in most checkpoint inhibitor trials. We evaluated the efficacy and safety of nivolumab in metastatic renal cell carcinoma (mRCC) patients with or without chronic HCV infection. METHODS: In a matched cohort study, data were collected from 174 patients, retrospectively. All patients had clear-cell mRCC, chronic HCV infection (case study group), no evidence of other malignancy or cirrhosis, and had received nivolumab (3 mg/kg every 2 weeks) until disease progression or unacceptable toxicity. Quantitation of HCV RNA in plasma samples was performed before and during treatment with nivolumab with the automated HCV test (Hoffmann-La Roche, Switzerland). The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and rate of grade 3-4 adverse events in study and control cohorts. RESULTS: A total of 44 matched patients were included. Groups were well balanced. HCV-infected patients had significantly longer OS and PFS. Median OS was 27.5 (95% CI 25.3-29.7) and 21.7 (20.3-23.1) in study and control groups, respectively (P = 0.005). Median PFS was 7.5 (5.7-9.3) and 4.9 (4-5.8) (P = 0.013). Despite no differences in ORR between groups (27% vs. 23%, P = 0.7), patients with HCV had significantly more durable responses (P = 0.01). Nivolumab was well tolerated in all HCV-positive patients. No unexpected toxicity was observed. Assessment of viral load during nivolumab therapy was available in 14 of 22 (64%) patients with HCV. Nivolumab did not significantly impact HCV concentration (mean change 210 IU/ml, P = 0.82) in the absence of antiviral therapy. CONCLUSIONS: The efficacy and safety profiles observed in this study support the administration of nivolumab in mRCC patients infected with HCV and warrant further investigation.

Population-based Prostate Cancer Screening in Kazakhstan.

BACKGROUND: Issues of mass screening for prostate cancer rather controversial since 2013 in 11 regions of Kazakhstan introduced a population-based screening for prostate cancer, so we need to evaluate its results. METHODS: In different regions of Kazakhstan during 2013-2015, a total of 321548 prostate-specific antigens (PSA) were determined in men aged 50-66 yr, under the Prostate Health Index (PHI) and transrectal ultrasonography (TRUS) guided prostate biopsy with histological examination. RESULTS: PSA level up to 4 ng/ml in 310870 (96.7%) men, PSA level between 4 and 10 ng/ml in 8 624 (2.7%) men, PSA level above 10 ng/ml in 2054 (0.6%) men. PHI was identified in 5716 (1.8%) men, of which 2867 cases were with PHI ≥ 25 (35.9%). Totally, 3680 biopsies (1.1%) of the prostate were performed. As part of the screening, 2870 cases (0.88%) of benign prostatic hyperplasia and prostatic intraepithelial neoplasia were found. Of 742 cases of prostate cancer (0.23%) were revealed. The stages of prostate cancer screening were as follows: stage I in 172 men (23.2%), stage II in 444 men (59.8%), stage III in 98 men (13.2%) and stage IV in 28 (3.8%) men. The indicators of prostate cancer early diagnosis in the I-II stages were bigger in the "screening regions" than in the "traditional diagnostics" regions: RR 1.35 95% CI (1.24 - 1.46), OR 1.84 95% CI (1.58-2.15). Prostate cancer was detected at I-II stages in the "screening" regions only by screening vs traditional diagnostics, with RR 1.64 95% CI (1.56 - 1.73), OR 4.77 95% CI (3.87-5.87). CONCLUSION: Implementation of screening can improve the diagnosis of prostate cancer in the early stages.