Open-Label, Single-Arm Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Clear Cell Renal Cell Carcinoma.

PURPOSE: Pembrolizumab, a programmed death 1 inhibitor, demonstrated promising single-agent activity in untreated patients with various cancer types. The phase II KEYNOTE-427 study evaluated efficacy and safety of single-agent pembrolizumab in treatment-naive patients with advanced clear cell renal cell carcinoma (ccRCC; cohort A) and advanced non-ccRCC (cohort B). Results of cohort A are reported. METHODS: In this open-label, single-arm phase II study, patients with advanced ccRCC received pembrolizumab 200 mg every 3 weeks for ≤ 24 months. The primary end point was objective response rate by RECIST, version 1.1. RESULTS: In the total population (N = 110), median time from enrollment to data cutoff was 35.9 (range, 29.5-40.3) months. Objective response rate was 36.4% with four (3.6%) complete responses and 36 (32.7%) partial responses; disease control rate was 58.2% (95% CI, 48.4 to 67.5). Most patients (68.2%) had a decrease in target lesions, including 30.9% with a reduction ≥ 60%. Median duration of response was 18.9 (range, 2.3-37.6+) months; 64.1% of responders had a response ≥ 12 months (Kaplan-Meier). Median progression-free survival was 7.1 months (95% CI, 5.6 to 11.0). Median overall survival was not reached; 12-month and 24-month overall survival rates were 88.2% and 70.8%, respectively. Durable responses were observed across all International Metastatic RCC Database Consortium categories. Grade 3-5 treatment-related adverse events were reported in 30.0% of patients, of which colitis and diarrhea were most frequent. CONCLUSION: Single-agent pembrolizumab showed promising antitumor activity as a first-line treatment in patients with advanced ccRCC, with durable responses across International Metastatic RCC Database Consortium categories. Safety and tolerability profile of pembrolizumab monotherapy was comparable to what has been previously described in other tumor types

Safety and efficacy of subcutaneous and continuous intravenous infusion rIL-2 in patients with metastatic renal cell carcinoma

Safety and efficacy of subcutaneous and continuous intravenous infusion rIL-2 in patients with metastatic renal cell carcinoma A retrospective analysis was conducted on data from four open- label, nonrandomised, phase II trials of recombinant interleukin-2 (rlL-2) in patients with metastatic renal cell carcinoma to compare the safety and efficacy of administration by subcutaneous (s.c.) and continuous intravenous (c.i.v.) infusion (n = 103 s.c. and n = 225 c.i.v.). No statistically significant differences were found between the cohorts in terms of overall response rate (s.c.: 13.6% vs c.i.v.: 12.4%, P = 0.77), response duration (s,c.: 9.8 months vs c.i.v.: 10.1 months, P = 0.99), and overall survival (P = 0.08). Compared with c.i.v. administration, more patients in the s.c. cohort experienced stable disease (50.5 vs 29.8%) and fewer underwent disease progression (35.0 vs 43.6%). Subcutaneous administration was associated with a significantly lower incidence of grade 3 or 4 adverse events (46 vs 76%; P < 0.001), and fewer s.c. patients required dose reductions because of toxicity (20 vs 82%). At the doses and within the schedules tested, this comparative analysis did not detect any difference in efficacy between s.c. and c.i.v. administration of rIL-2 in terms of overall survival, duration of response and response rate in patients with metastatic renal cell carcinoma. However, s.c. delivery of rIL-2 was associated with improved tolerability

Pegylated-liposomal doxorubicin and oral topotecan in eight children with relapsed high-grade malignant brain tumors

The schedule of PEG-liposomal doxorubicin with 30-40 mg/m(2) every 4 weeks in combination with oral topotecan resulted in tumor response, but the toxicity was high. An individualized increasing dose of PEG-liposomal doxorubicin 10-20 mg/m(2) every two weeks is now recommended