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Considering clinical benefits of new combination therapies for metastatic renal-cell carcinoma (mRCC), this study aims to calculate the number needed to treat (NTT) and the cost of preventing an event (COPE) for pembrolizumab plus axitinib (P + A), and nivolumab plus ipilimumab (N + I) as first-line treatments, from the Brazilian private perspective. Overall survival (OS) and progression-free survival (PFS) data for intermediate- and poor-risk groups were obtained from KEYNOTE-426 and CHECKMATE-214 trials for P + A and N + I, respectively, versus sunitinib as mRCC first-line treatment. Considering a 12-month time horizon, 6 patients should be treated with P + A to prevent one death with sunitinib use, resulting in a COPE of 3,893,903 BRL. Using N + I, NNT for 12-month OS rate was 13 compared to sunitinib, with a COPE of 6,357,965 BRL. Regarding PFS data, NNT was also 6 when comparing P + A versus sunitinib, with an estimated COPE of 3,893,903 BRL. Estimated NNT was 20 comparing N + I and sunitinib, resulting in a COPE of 10,172,744 BRL. Cost differences between two treatment options, reached more than 6 million BRL for PFS, and 2 million BRL for OS. At the 12-month landmark, P + A suggests better economic scenario versus N + I as first-line mRCC treatment option for intermediate- and poor-risk groups, through an indirect comparison using sunitinib as a common comparator.

PD-L1 (CD274) amplification occurs in a small subset of malignancies and may predict anti-PD-1/PD-L1 immunotherapy responsiveness. We hypothesized that both copy number (CN) and focality of cancer-related PD-L1 amplifications impact protein expression, and, thus, analyzed solid tumors that underwent comprehensive genomic profiling between March 2016 and February 2022 at Foundation Medicine. PD-L1 CN alterations were detected using a comparative genomic hybridization-like method. PD-L1 CN changes were correlated with PD-L1 protein expression (DAKO 22C3 antibody) by immunohistochemistry (IHC). Overall, 60,793 samples were analyzed (most frequent histologies: lung adenocarcinoma (20%), colon adenocarcinoma (12%), lung squamous carcinoma (8%)). Using a definition of CD274 CN ≥ specimen ploidy +4 (6 copies), 1.21% of tumors (738/60,793) were PD-L1 amplified. Focality category distribution was as follows

Immune checkpoint inhibitors may be associated with multiple immune-related toxicities. Cardiovascular adverse effects are underreported in clinical trials.We conducted a systematic review and meta-analysis to evaluate cardiovascular adverse effects incidence among patients with solid tumors receiving immune checkpoint inhibitors in randomized clinical trials and the relative risk of presenting these effects compared to placebo or best supportive care. The search was conducted through MEDLINE, Embase, and Scopus databases from January 1st, 2010 until July 1st, 2020. Outcomes were reported following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.57 randomized clinical trials including 12,118 patients were included. All grade CV AEs incidence rate was 8.32% (95% CI = 6.35%-10.53%). When only grade 3-5 CV AEs were considered, ICIs were significantly associated with increased risk than placebo or BSC (RR = 1.36; 95% CI = 1.06-1.73; p = 0.01).This meta-analysis corroborates the hypothesis of increased CV risk related to immune checkpoint inhibitors.

Purpose The outcome of RCC has improved considerably in the last few years, and the treatment options have increased. LACOG-GU and LARCG held a consensus meeting to develop guidelines to support the clinical decisions of physicians and other health professionals involved in the care of RCC patients. Methods Eighty questions addressing relevant advanced RCC treatments were previously formulated by a panel of experts. The voting panel comprised 26 specialists from the LACOG-GU/LARCG. Consensus was determined as 75% agreement. For questions with less than 75% agreement, a new discussion was held, and consensus was determined by the majority of votes after the second voting session. Results The recommendations were based on the highest level of scientific evidence or by the opinion of the RCC experts when no relevant research data were available. Conclusion This manuscript provides guidance for advanced RCC treatment according to the LACOG-GU/LARCG expert recommendations. Electronic supplementary material The online version of this article (10.1007/s00432-020-03236-4) contains supplementary material, which is available to authorized users.

INTRODUCTION AND OBJECTIVES:There are two mainly pathways to gain a new medical device approval by the Food and Drug Administration (FDA): the Premarket Approval Application and the Premarket Notif...

Background Bevacizumab is currently approved for the treatment of several malignancies. Haematologic toxicities are not among the main concerns associated with bevacizumab, but they have been occasionally reported. We performed a meta-analysis to determine the incidence and risk of haematologic toxicities associated with bevacizumab. Methods Pubmed databases from 1966 to September 2010 were searched for studies reported, as well as American Society of Clinical Oncology meetings. Bevacizumab randomised clinical trials with adequate safety data profile were included. Statistical analyses were conducted to calculate the summary incidence, relative risk (RR) and 95% confidence intervals (CI). Results 15,263 patients were included. The incidence of bevacizumab-associated all-grade and high-grade haematologic toxicities were, respectively: anaemia: 18.7% and 3.9%; neutropenia: 25.0% and 18.5%; and thrombocytopenia: 13.9% and 3.4%. Febrile neutropenia incidence was 3.8%. Compared to placebo/control arms, bevacizumab was associated with a decreased risk of all-grade (RR = 0.81; 95%CI 0.68–0.96; p = .016) and high-grade (RR = 0.73; 95%CI 0.60–0.89; p = .002) anaemia, and increased risks of all-grade (RR = 1.15; 95%CI 1.01–1.30; p = .033) and high-grade (RR = 1.08; 95%CI 1.02–1.13; p = .005) neutropenia, all-grade thrombocytopenia (RR = 1.22; 95%CI 1.00–1.48; p = .047) and febrile neutropenia (RR = 1.31; 95%CI 1.08–1.58; p = .006). Conclusions Bevacizumab is associated with a lower risk of anaemia and increased risks of neutropenia, thrombocytopenia and febrile neutropenia.

Introduction and objective Retroperitoneal lymph node dissection (RPLND) is indicated for patients with non-seminomatous germ cell tumor (NSGCT) with residual disease after chemotherapy. Although the gold standard approach is still the open surgery, few cases of robot-assisted laparoscopic RPLND have been described. Herein, we aim to present the surgical technique for robot-assisted laparoscopic RPLND. Patient and method A 30 year-old asymptomatic man presented with left testicular swelling for 2 months. Physical examination revealed an enlarged and hard left testis. Alpha-fetoprotein (>1000ng/mL) and beta-HCG (>24.000U/L) were increased. Beta-HCG increased to >112.000U/L in less than one month. The patient underwent a left orchiectomy. Pathological examination showed a mixed NSGCT (50% embryonal carcinoma; 30% teratoma; 10% yolk sac; 10% choriocarcinoma). Computed tomography scan revealed a large tumor mass close to the left renal hilum (10x4x4cm) and others enlarged paracaval and paraortic lymph nodes (T2N3M1S3-stage III). Patient was submitted to 4 cycles of BEP with satisfactory response. Residual mass was suggestive of teratoma. Based on these findings, he was submitted to a robot-assisted RPLND. Results RPLND was uneventfully performed. Operative time was 3.5 hours. Blood loss was minimal, and there were no intra- or postoperative complications. The patient was discharged from hospital in the 1st postoperative day. Pathological examination showed a pure teratoma. After 6 months of follow-up, patient is asymptomatic with an alpha-fetoprotein of 2.9ng/mL and an undetectable beta-HCG. Conclusion Robot-assisted laparoscopic RPLND is a feasible procedure with acceptable morbidity even for post chemotherapy patients when performed by an experienced surgeon.