Pembrolizumab plus Olaparib in Patients with Metastatic Castration-resistant Prostate Cancer: Long-term Results from the Phase 1b/2 KEYNOTE-365 Cohort A Study

Metastatic castration-resistant prostate cancer; Olaparib; PembrolizumabCáncer de próstata metastásico resistente a la castración; Olaparib; PembrolizumabCàncer de pròstata metastàtic resistent a la castració; Olaparib; PembrolizumabBackground Pembrolizumab and olaparib have shown single-agent activity in patients with previously treated metastatic castration-resistant prostate cancer (mCRPC). Objective To evaluate the efficacy and safety of pembrolizumab plus olaparib in mCRPC. Design, setting, and participants Cohort A of the phase 1b/2 KEYNOTE-365 study enrolled patients with molecularly unselected, docetaxel-pretreated mCRPC whose disease progressed within 6 mo of screening. Intervention Pembrolizumab 200 mg intravenously every 3 wk plus olaparib 400-mg capsule or 300-mg tablet orally twice daily. Outcome measurements and statistical analysis The primary endpoints were safety, confirmed prostate-specific antigen (PSA) response rate, and objective response rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, by blinded independent central review. The secondary endpoints included radiographic progression-free survival (rPFS) and overall survival (OS). Results and limitations Of 104 enrolled patients, 102 were treated. The median age was 70 yr (interquartile range [IQR], 65–76), and 59 patients (58%) had measurable disease as per RECIST v1.1. The median time from the first dose to database cutoff was 24 mo (IQR, 22–47). The confirmed PSA response rate was 15%. The confirmed ORR was 8.5% (five partial responses) for patients with measurable disease. The median rPFS was 4.5 mo (95% confidence interval [CI], 4.0–6.5) and median OS was 14 mo (95% CI, 10.4–18.2). Clinical activity was consistent across the programmed death ligand 1 (PD-L1)-positive and homologous recombination repair mutation subgroups. Treatment-related adverse events (TRAEs) occurred in 93 patients (91%). Grade 3–5 TRAEs occurred in 49 patients (48%). Six deaths (5.9%) were due to adverse events; two (myocardial infarction and unknown cause) were attributed to treatment. Limitations of the study include the single-arm design. Conclusions Pembrolizumab plus olaparib had a safety profile consistent with the profiles of the individual agents and demonstrated antitumor activity in previously treated patients with molecularly unselected, docetaxel-pretreated mCRPC

Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial

Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population

Surveillance de l’hypertension artérielle chez les patients traités par anti-angiogénique par voie orale en pratique quotidienne

International audienceObjective - The aim of this study is to measure the monitoring and the incidence of renovascular effects of angiogenesis inhibitors in real population. Method - Are included in this descriptive, monocentric, practical study, patients of 18 years old and more, orally treated by angiogenesis inhibitors and monitored in consultation by clinician nurses. The main interest variable is the incidence of hypertension at three months of treatment. Results - From January, 2011 to July, 2014, 324 patients have been included, whose 53% are men. Mean age is 62±13 years old. Antecedents are: 37% of hypertension, 17% of chronic renal insufficiency, 21% of nephrectomy, 13% of diabetes. Most frequent cancers are kidney (31%), liver (23%) and breast (16%). Most used molecules are: sorafenib (30%), sunitinib (23%) and everolimus (16%). Blood pressure has been measured at the beginning of the treatment in 157 patients (48%). Among them, during the first three months of treatment, 55 (35%) present hypertension according to the oncological definition and 59 (38%) according to the classical definition; 30 patients (19%) are considered as hypertensive according to only one of the two definitions. In multivariable analysis, variables significantly associated with hypertension are: age (OR=1.04; 95% CI 1.02-1.08; P<0.01) and antecedent of nephrectomy (OR=4.29; 95%CI 1.86-9.92; P<0.01). Conclusion - In this cohort, only 48% of the patients had blood pressure determination before treatment. Hypertension under angiogenesis inhibitors is probably underestimated. Age and antecedent of nephrectomy seem to be correlated with the occurrence of hypertension

Aortic dissection in a patient treated by sunitinib for metastatic renal cell carcinoma.

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Treatment with Sunitinib Enabled Complete Resection of Massive Lymphadenopathy not Previously Amenable to Excision in a Patient with Renal Cell Carcinoma.

International audienceWe present a case of previously unresectable lymphadenopathy in a patient with renal cell carcinoma treated with sunitinib. Complete resection of a 15-cm left renal cell carcinoma was initially impossible due to massive retroperitoneal disease and encasement of the great vessels and mesenteric vessels. Residual retroperitoneal disease from a radical nephrectomy was treated with the oral, multitargeted receptor tyrosine kinase inhibitor, sunitinib. Tumour shrinkage following five cycles of treatment allowed uncomplicated complete resection of the lymphadenopathy. Follow-up after 6 mo showed no evidence of disease recurrence

Is home blood pressure monitoring feasible and well accepted in nephrectomized patients for renal cancer? (STAFF study).

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Improving the pre-screening of eligible patients in order to increase enrollment in cancer clinical trials.

The trials evaluated in this study were previously registered with clinicaltrials.gov (registration number: NCT00104741 webcite on 3 March 2005; NCT00104715 webcite on 3 March 2005; NCT00423475 webcite on 16 January 2007; and NCT00667069 webcite on 24 April 2008).International audienceBackground. The performance of randomized controlled trials (RCTs) is often hindered by recruitment difficulties. This study aims to explore the pre-screening phase of four prostate cancer RCTs to identify the impact of a systematic pre-selection of eligible patients for RCT recruitment.Methods. The pre-screening of four RCTs opened at the Comprehensive Cancer Center in Rennes was analyzed retrospectively (French Genitourinary Tumor Group (GETUG) 14, 15, 16, and 17). Data were extracted from electronic multidisciplinary cancer (MDC) reports and manually completed by physicians and medical secretaries. These data were the main source of information for clinicians to discuss treatment alternatives during MDC sessions. The pre-screening decisions made by the clinicians during these MDC meetings were compared with those made after a systematic review of the MDC reports by a clinical research assistant (CRA). Any inconsistencies in decisions between the CRA and the MDC physicians were corrected by the principal investigator (PI).Results. The pre-screening rate was 9.1% during the MDC meetings, while it was estimated to be 12.9% after the final review by the PI, and 29% after the systematic review by the CRA. The study showed that 77% and 67% of the MDC reports did not mention clinical and pathological Tumor, lymph node and metastasis classification of malignant tumors (TNM) staging, respectively, and that 35 of the CRA’s 47 proposals rejected by the PI concerned implicit information (not specified in the MDC reports). Only one patient was proposed by the PI, and none by the CRA.Conclusions. These results confirm that pre-screening could be improved by a systematic review of the medical reports. They also highlight the fact that missing data in electronic MDC reports leads to over-enrollment of non-eligible patients, but not to over-exclusion of eligible patients. Thus, our study confirms the potential gain in using semi-automated pre-selection of MDC reports, in order to avoid missing out on patients eligible for RCTs

Phase II study of axitinib for downstaging cT2a to cT1 renal tumors for allowing partial nephrectomy (AXIPAN).

International audienceno abstrac

Phase II study of axitinib for downstaging cT2a to cT1 renal tumors for allowing partial nephrectomy (AXIPAN).

International audienceno abstrac