Angiogenic and Immune-Related Biomarkers and Outcomes Following Axitinib/Pembrolizumab Treatment in Patients with Advanced Renal Cell Carcinoma.

PURPOSE: Combined axitinib/pembrolizumab is approved for advanced renal cell carcinoma (aRCC). This exploratory analysis examined associations between angiogenic and immune-related biomarkers and outcomes following axitinib/pembrolizumab treatment. PATIENTS AND METHODS: Prospectively defined retrospective correlative exploratory analyses tested biospecimens from 52 treatment-naïve patients receiving axitinib and pembrolizumab (starting doses 5 mg twice daily and 2 mg/kg respectively, every 3 weeks). Tumor tissue, serum, and whole blood samples were collected at baseline, at cycle 2 day 1 (C2D1), and end of treatment (EOT) for blood-based samples. Clinical outcomes were objective response rate (ORR) and progression-free survival (PFS). RESULTS: Higher baseline tumor levels of CD8 showed a trend toward longer PFS (HR 0.4; P = 0.091). Higher baseline serum levels of CXCL10 (P = 0.0197) and CEACAM1 (P = 0.085) showed a trend toward better ORR and longer PFS, respectively. Patients for whom IL6 was not detected at baseline had longer PFS versus patients for whom it was detected (HR 0.4; P = 0.028). At C2D1 and/or EOT, mainly immune-related biomarkers showed any association with better outcomes. The genes CA9 (P = 0.084), HIF1A (P = 0.064), and IFNG (P = 0.073) showed trending associations with ORR, and AKT3 (P = 0.0145), DDX58 (P = 0.0726), GZMA (P = 0.0666), LCN2 (NGAL; P = 0.0267), and PTPN11 (P = 0.0287) with PFS. CONCLUSIONS: With combined axitinib/pembrolizumab treatment in patients with aRCC, mostly immune-related biomarkers are associated with better treatment outcomes. This exploratory analysis has identified some candidate biomarkers to consider in future prospective testing.

Sample size considerations when groups are the appropriate unit of analysis.

This article discusses issues to be considered by nurse researchers when groups should be used as the unit of randomization. Advantages and disadvantages are presented, with statistical calculations needed to determine the effective sample size. Examples of these concepts are presented using data from the Black Cosmetologists Promoting Health Program. Different hypothetical scenarios and their impact on sample size are also presented. Given the complexity of calculating the sample size when using groups as the unit of randomization, it is advantageous for researchers to work closely with statisticians when designing and implementing studies that anticipate the use of groups as the unit of randomization.

Evidence of real-world effectiveness of a telephone quitline for smokers.

BACKGROUND: Telephone services that offer smoking-cessation counseling (quitlines) have proliferated in recent years, encouraged by positive results of clinical trials. The question remains, however, whether those results can be translated into real-world effectiveness. METHODS: We embedded a randomized, controlled trial into the ongoing service of the California Smokers' Helpline. Callers were randomly assigned to a treatment group (1973 callers) or a control group (1309 callers). All participants received self-help materials. Those in the treatment group were assigned to receive up to seven counseling sessions; those in the control group could also receive counseling if they called back for it after randomization. RESULTS: Counseling was provided to 72.1 percent of those in the treatment group and 31.6 percent of those in the control group (mean, 3.0 sessions). The rates of abstinence for 1, 3, 6, and 12 months, according to an intention-to-treat analysis, were 23.7 percent, 17.9 percent, 12.8 percent, and 9.1 percent, respectively, for those in the treatment group and 16.5 percent, 12.1 percent, 8.6 percent, and 6.9 percent, respectively, for those in the control group (P<0.001). Analyses factoring out both the subgroup of control subjects who received counseling and the corresponding treatment subgroup indicate that counseling approximately doubled abstinence rates: rates of abstinence for 1, 3, 6, and 12 months were 20.7 percent, 15.9 percent, 11.7 percent, and 7.5 percent, respectively, in the remaining subjects in the treatment group and 9.6 percent, 6.7 percent, 5.2 percent, and 4.1 percent, respectively, in the remaining subjects in the control group (P<0.001). Therefore, the absolute difference in the rate of abstinence for 12 months between the remaining subjects in the treatment and control groups was 3.4 percent. The 12-month abstinence rates for those who made at least one attempt to quit were 23.3 percent in the treatment group and 18.4 percent in the control group (P<0.001). CONCLUSIONS: A telephone counseling protocol for smoking cessation, previously proven efficacious, was effective when translated to a real-world setting. Its success supports Public Health Service guidelines calling for greater availability of quitlines.