Updated efficacy results from the JAVELIN Renal 101 trial: first-line avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma.

BACKGROUND: The phase 3 JAVELIN Renal 101 trial (NCT02684006) demonstrated significantly improved progression-free survival (PFS) with first-line avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma (aRCC). We report updated efficacy data from the second interim analysis. PATIENTS AND METHODS: Treatment-naive patients with aRCC were randomized (1 : 1) to receive avelumab (10 mg/kg) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The two independent primary end points were PFS and overall survival (OS) among patients with programmed death ligand 1-positive (PD-L1+) tumors. Key secondary end points were OS and PFS in the overall population. RESULTS: Of 886 patients, 442 were randomized to the avelumab plus axitinib arm and 444 to the sunitinib arm; 270 and 290 had PD-L1+ tumors, respectively. After a minimum follow-up of 13 months (data cut-off 28 January 2019), PFS was significantly longer in the avelumab plus axitinib arm than in the sunitinib arm {PD-L1+ population: hazard ratio (HR) 0.62 [95% confidence interval (CI) 0.490-0.777]}; one-sided P < 0.0001; median 13.8 (95% CI 10.1-20.7) versus 7.0 months (95% CI 5.7-9.6); overall population: HR 0.69 (95% CI 0.574-0.825); one-sided P < 0.0001; median 13.3 (95% CI 11.1-15.3) versus 8.0 months (95% CI 6.7-9.8)]. OS data were immature [PD-L1+ population: HR 0.828 (95% CI 0.596-1.151); one-sided P = 0.1301; overall population: HR 0.796 (95% CI 0.616-1.027); one-sided P = 0.0392]. CONCLUSION: Among patients with previously untreated aRCC, treatment with avelumab plus axitinib continued to result in a statistically significant improvement in PFS versus sunitinib; OS data were still immature. CLINICAL TRIAL NUMBER: NCT02684006.

Patient-reported quality-of-life analysis of radium-223 dichloride from the phase III ALSYMPCA study.

BACKGROUND: Radium-223 dichloride (radium-223), a first-in-class α-emitting radiopharmaceutical, is recommended in both pre- and post-docetaxel settings in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases based on overall survival benefit demonstrated in the phase III ALSYMPCA study. ALSYMPCA included prospective measurements of health-related quality of life (QOL) using two validated instruments: the general EuroQoL 5D (EQ-5D) and the disease-specific Functional Assessment of Cancer Therapy-Prostate (FACT-P). PATIENTS AND METHODS: Analyses were conducted to determine treatment effects of radium-223 plus standard of care (SOC) versus placebo plus SOC on QOL using FACT-P and EQ-5D. Outcomes assessed were percentage of patients experiencing improvement, percentage of patients experiencing worsening, and mean QOL scores during the study. RESULTS: Analyses were carried out on the intent-to-treat population of patients randomized to receive radium-223 (n = 614) or placebo (n = 307). The mean baseline EQ-5D utility and FACT-P total scores were similar between treatment groups. A significantly higher percentage of patients receiving radium-223 experienced meaningful improvement in EQ-5D utility score on treatment versus placebo {29.2% versus 18.5%, respectively; P = 0.004; odds ratio (OR) = 1.82 [95% confidence interval (CI) 1.21-2.74]}. Findings were similar for FACT-P total score [24.6% versus 16.1%, respectively; P = 0.020; OR = 1.70 (95% CI 1.08-2.65)]. A lower percentage of patients receiving radium-223 experienced meaningful worsening versus placebo measured by EQ-5D utility score and FACT-P total score. Prior docetaxel use and current bisphosphonate use did not affect these findings. Treatment was a significant predictor of EQ-5D utility score, with radium-223 associated with higher scores versus placebo (0.56 versus 0.50, respectively; P = 0.002). Findings were similar for FACT-P total score (99.08 versus 95.22, respectively; P = 0.004). CONCLUSIONS: QOL data from ALSYMPCA demonstrated that improved survival with radium-223 is accompanied by significant QOL benefits, including a higher percentage of patients with meaningful QOL improvement and a slower decline in QOL over time in patients with CRPC.

The parasite assemblage in the spiral intestine of the shark Mustelus canis.

The parasite assemblage in the 8 chambers of the spiral intestine of 49 specimens of the shark Mustelus canis collected from Long Island Sound and off the coast of Virginia was investigated. Assemblages within host individuals were composed of up to 3 of 4 species of cestodes: the trypanorhynch species Prochristianella tumidula and Lacistorhynchus tenuis and the hooked tetraphyllidean species Calliobothrium verticillatum and Calliobothrium lintoni. Each individual shark hosted 1-3 (mean = 2.17) tapeworm species and 1-166 (mean = 34.3) tapeworm individuals. The assemblage consisted of 2 core species, 1 secondary species, and 1 satellite species. Analysis of variance (ANOVA) revealed significant differences among the areas of the 8 intestinal chambers. ANOVAs of worm density among chambers revealed that each of the 4 species exhibited site specificity within the spiral intestine. Least significant difference analysis revealed that each of the species, except C. verticillatum, was usually found in the anterior 3 chambers. Calliobothrium verticillatum was more commonly found in the middle region of the organ, centered around chamber 4. Horn's information index indicated that L. tenuis and C. lintoni had the greatest amount of overlap within the spiral intestine and the congeners C. lintoni and C. verticillatum had the least amount of overlap. No evidence of interaction among the species in this assemblage was found. In cases where observations could be made, neither cestode total length nor location within the spiral intestine appeared to be affected by the presence of other individuals or species respectively. There was some evidence of underutilized space; the posteriormost chamber was vacant in all 49 sharks examined and 91.8% of sharks had at least 2 vacant chambers. Linear regression revealed no relationship between shark total length and either total number of worms or total number of individuals of each of the 4 species of cestodes. The chi-square test revealed no evidence that the 4 species do not occur independently among host individuals. The number of species and number of individuals in M. canis were low when compared to the marine fish Sebastes nebulosus. These values for M. canis more closely resemble values for freshwater fishes. The comparatively much greater host specificity of these tapeworms may at least partially account for this difference. We propose that site specificity may have a phylogenetic component, in a manner similar to that of host specificity.