VFL demonstrates a survival advantage in second-line treatment for advanced TCCU. Consistency of results exists with significant and meaningful benefit over all efficacy parameters. Safety profile is acceptable, and therefore, VFL seems to be a reasonable option for TCCU progressing after first-line platinum-based therapy.

PURPOSE The present study sought to identify pretreatment prognostic factors for overall survival (OS) in patients with metastatic transitional cell carcinoma of the urothelial tract (TCCU) who experienced treatment failure with the first-line, platinum-based regimen included in the phase III vinflunine trial. PATIENTS AND METHODS In total, 370 patients with platinum-refractory TCCU were included in this analysis. Potential prognostic factors were recorded prospectively. Univariate analysis was used to identify clinical and laboratory factors that significantly impact survival. Multivariate analysis was used to identify independent prognostic factors, and bootstrap analysis was performed for internal validation, forming a prognostic model. External validation was performed on the phase II vinflunine study CA183001. RESULTS Multivariate analysis and the internal validation identified Eastern Cooperative Oncology Group performance status (PS) more than 0, hemoglobin level less than 10 g/dL, and the presence of liver metastasis as the main adverse prognostic factors for OS. External validation confirmed these prognostic factors. Four subgroups were formed based on the presence of zero, one, two, or three prognostic factors; the median OS times for these groups were 14.2, 7.3, 3.8, and 1.7 months (P < .001), respectively. CONCLUSION We identified and both internally and externally validated three adverse risk factors (PS, hemoglobin level, and liver metastasis) that predict for OS and developed a scoring system that classifies patients with platinum-refractory disease on second-line chemotherapy into four risk groups with different outcome. Similar to the first-line setting, the presence of visceral metastases and poor PS predict a worse prognosis. These factors, together with low hemoglobin, can be used for prognostication and future patient stratification in clinical trials.

With a 4% overall response rate (95% CI, 0.5 to 12.8) and an 11% rate of third-party-verified tumor regression (overall response rate + minor response), ET-743 has a 24% 6-month disease progression control rate, confirming evidence of antitumoral activity and a manageable safety profile in patients experiencing disease progression with pretreated soft tissue sarcoma.

The updated OS data confirm the positive treatment effect of vinflunine on survival that was previously reported. These results are consistent over time and confirm that vinflunine is a valuable option for second-line treatment in patients with advanced TCCU after failure of platinum-based regimens.

Background: GBR 830 is a humanized mAb against OX40, a costimulatory receptor on activated T cells. OX40 inhibition might have a therapeutic role in T cell-mediated diseases, including atopic dermatitis (AD). Objective: This exploratory phase 2a study investigated the safety, efficacy, and tissue effects of GBR 830 in patients with AD. Methods: Patients with moderate-to-severe AD (affected body surface area, > _10%; Eczema Area and Severity Index score, > _12; and inadequate response to topical treatments) were randomized 3:1 to 10 mg/kg intravenous GBR 830 or placebo on day 1 (baseline) and day 29. Biopsy specimens were collected (n 5 40) at days 1, 29, and 71. Primary end points included treatment-emergent adverse events (TEAEs) and changes from baseline in biomarkers (epidermal hyperplasia/cytokines) at days 29 and 71. Results: GBR 830 was well tolerated, with equal TEAE distribution (GBR 830, 63.0% [29/46]; placebo, 63.0% [10/16]). One serious TEAE in the GBR 830 group was deemed unrelated to study drug. At day 71, the proportion of intent-to-treat subjects achieving 50% or greater improvement in Eczema Area and Severity Index score was greater with GBR 830 (76.9% [20/26]) versus placebo (37.5% [3/8]). GBR 830 induced significant progressive reductions in T H 1 (IFN-g/CXCL10), T H 2 (IL-31/CCL11/CCL17), and T H 17/T H 22 (IL-23p19/IL-8/ S100A12) mRNA expression in lesional skin. Significant progressive reductions until day 71 in the drug group were seen in OX40 1 T cells and OX40L 1 dendritic cells (P < .001). Hyperplasia measures (thickness/keratin 16/Ki67) showed greater reductions with GBR 830 (P < .001). Conclusions: Two doses of GBR 830 administered 4 weeks apart were well tolerated and induced significant progressive tissue and clinical changes until day 71 (42 days after the last dose), highlighting the potential of OX40 targeting in patients with AD.

This noninferiority phase III study showed similar efficacy end points for vinflunine and docetaxel. Despite higher rates of some adverse effects (anemia, abdominal pain, constipation, fatigue) the overall toxicity profile of vinflunine was manageable. Therefore, VFL may be another option in the second-line treatment of patients with advanced NSCLC.

ObjectiveTo study the impact of the prognostic factors liver metastasis (LM), anaemia (haemoglobin [Hb] <10 g/dL), Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥1 and time from previous chemotherapy (TFPC) on the activity of second-line therapy for advanced urothelial carcinoma (UC). Patients and MethodsTwelve phase II trials evaluating second-line chemotherapy and/or biological characteristics (n = 748) in patients with progressive disease were pooled.Progression-free survival (PFS) was defined as tumour progression or death from any cause.The PFS rate at 6 months (PFS6) was defined from the date of registration and calculated using the Kaplan-Meier method.Response rate (RR) was defined using Response Evaluation Criteria in Solid Tumours (RECIST) 1.0.A nomogram predicting PFS6 was constructed using the RMS software package in R (http://www.r-project.org). ResultsData regarding progression, anaemia, LM, ECOG-PS and TFPC were available from 570 patients in nine phase II trials.The overall median PFS was 2.7 months, PFS6 was 22.2% (95% confidence interval 18.8-25.9) and the RR was 17.5% (95% CI: 14.5-20.9%).For every unit increase in risk group, the hazard of progression in 6 months increased by 41% and the odds of response decreased by 48%.A nomogram was constructed to predict PFS6 on an individual patient level.The model was internally validated and was shown to have acceptable calibration performance. ConclusionsThe RR and PFS6 vary as a function of baseline prognostic factors in patients receiving second-line therapy for advanced UC.

Background: GSP301 is an investigational fixed-dose combination nasal spray of olopatadine hydrochloride (antihistamine) and mometasone furoate (corticosteroid). Objective: To evaluate efficacy and safety of GSP301 in patients with seasonal AR (SAR). Methods: In this phase 2, double-blind, parallel-group study, patients (12 years of age) with SAR were equally randomized to twice-daily GSP301 (olopatadine 665 mg and mometasone 25 mg), once-daily GSP301 (olopatadine 665 mg and mometasone 50 mg), twice-daily or once-daily olopatadine monotherapy (665 mg), mometasone monotherapy (twice-daily 25 mg or once-daily 50 mg), or placebo for 14 days. The primary endpointdmean change from baseline in morning and evening reflective Total Nasal Symptom Score (rTNSS)dwas analyzed using analysis of covariance (ANCOVA; P < .05 ¼ statistically significant). Average morning and evening 12-hour instantaneous TNSS (iTNSS), ocular symptoms, individual symptoms, onset of action, quality of life, and adverse events (AEs) were also assessed. Results: A total of 1111 patients were randomized. Twice-daily GSP301 provided statistically significant and clinically meaningful rTNSS improvements vs placebo (P < .001), twice-daily olopatadine (P ¼ .049), and mometasone (P ¼ .004). Similar significant improvements in iTNSS were observed with twice-daily GSP301 vs placebo (P < .001) and twice-daily mometasone (P ¼ .007); improvements were not significant vs olopatadine (P ¼ .058). Once-daily GSP301 provided significant rTNSS and iTNSS improvements vs placebo and once-daily olopatadine (P < .01, all) but improvements were not significant vs mometasone. Treatment-emergent AEs rates were 10.8%, 9.5%, and 8.2%, with twice-daily GSP301, once-daily GSP301, and placebo, respectively. Conclusion: Twice-daily GSP301 treatment was efficacious and well tolerated, providing statistically significant and clinically meaningful improvements in rTNSS (primary endpoint) vs placebo and both monotherapies. Trial Registration: Clinicaltrials.gov Identifier NCT02318303