Comparison of Good Clinical Practice Inspection Processes for Marketing Applications Between the United States Food and Drug Administration and the European Medicines Agency.

Background: The U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) began collaboration on Good Clinical Practice (GCP) inspections for marketing applications since 2009.

Descriptive Analysis of Good Clinical Practice Inspection Findings from U.S. Food and Drug Administration and European Medicines Agency.

Background: The United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) have collaborated in good clinical practice (GCP) inspections since September 2009. The two agencies operate under different regulatory frameworks for GCP oversight. No systematic assessments of GCP inspection findings have been reported.

Cabozantinib plus Nivolumab Phase I Expansion Study in Patients with Metastatic Urothelial Carcinoma Refractory to Immune Checkpoint Inhibitor Therapy.

Purpose: This study investigated the efficacy and tolerability of cabozantinib plus nivolumab (CaboNivo) in patients with metastatic urothelial carcinoma (mUC) that progressed on checkpoint inhibition (CPI).

Patients And Methods: A phase I expansion cohort of patients with mUC who received prior CPI was treated with cabozantinib 40 mg/day and nivolumab 3 mg/kg every 2 weeks until disease progression/unacceptable toxicity. The primary goal was objective response rate (ORR) per RECIST v.

Analysis of the Association Between Adverse Events and Outcome in Patients Receiving a Programmed Death Protein 1 or Programmed Death Ligand 1 Antibody.

Purpose: To assess the relationship among tumor response rate, overall survival, and the development of related adverse events of special interest (AESIs) or related immune-mediated adverse events (imAEs) in patients with urothelial cancer treated with anti-programmed death protein 1 or ligand 1 (anti-PD-1/L1) antibodies.

Patients And Methods: We examined seven trials in 1,747 patients with metastatic or locally advanced urothelial cancer that led to approval of an anti-PD-1/L1 antibody. Five trials enrolled patients who had received prior platinum-based therapy, and two enrolled patients who were cisplatin ineligible.

FDA Approval Summary: Atezolizumab or Pembrolizumab for the Treatment of Patients with Advanced Urothelial Carcinoma Ineligible for Cisplatin-Containing Chemotherapy.

The U.S. Food and Drug Administration (FDA) granted accelerated approval to atezolizumab and pembrolizumab in April and May 2017, respectively, for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy.

Accelerating Early Access to Immunotherapies for Advanced Urothelial Carcinoma.

Within one year, five immunotherapies have been approved for the treatment of patients with locally advanced or metastatic urothelial cancer. The availability of these immunotherapies brings challenges to all stakeholders in the field. Additional research is needed to identify biomarkers that are predictive of individual patient response to different immunotherapies.

FDA Approval Summary: Atezolizumab for the Treatment of Patients with Progressive Advanced Urothelial Carcinoma after Platinum-Containing Chemotherapy.

Unlabelled: Until recently in the United States, no products were approved for second-line treatment of advanced urothelial carcinoma. On May 18, 2016, the U.S.

Phase II trial of docetaxel, bevacizumab, lenalidomide and prednisone in patients with metastatic castration-resistant prostate cancer.

Objective: To determine the safety and clinical efficacy of two anti-angiogenic agents, bevacizumab and lenalidomide, with docetaxel and prednisone.

Patients And Methods: Eligible patients with metastatic castration-resistant prostate cancer enrolled in this open-label, phase II study of lenalidomide with bevacizumab (15 mg/kg), docetaxel (75 mg/m(2) ) and prednisone (10 mg daily). Docetaxel and bevacizumab were administered on day 1 of a 3-week treatment cycle.

U.S. Food and Drug Administration Approval Summary: Enzalutamide for the Treatment of Patients With Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer.

The U.S. Food and Drug Administration approved enzalutamide for the treatment of patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC).

Food and Drug Administration process for development and approval of drugs and radiopharmaceuticals: treatments in urologic oncology.

Regulatory advice and assessment play an important role in the successful development of new drugs and radiopharmaceuticals for the treatment of urologic malignancies. Cooperation between the US Food and Drug Administration (FDA) and the pharmaceutical industry has led to the approval of more than 20 new urologic oncology products in the last 2 decades. Despite these advances, more effective treatments need to be developed and approved for the treatment of urologic malignancies.

FDA approval summary: vemurafenib for treatment of unresectable or metastatic melanoma with the BRAFV600E mutation.

On August 17, 2011, the U.S. Food and Drug Administration (FDA) approved vemurafenib tablets (Zelboraf, Hoffmann-LaRoche Inc.

Under-representation of racial minorities in prostate cancer studies submitted to the US Food and Drug Administration to support potential marketing approval, 1993-2013.

Background: US Food and Drug Administration (FDA) approval of new drugs depends on results from clinical trials that must be generalized to the US population. However, racial minorities are frequently under-represented in clinical studies. The enrollment of racial minorities was compared in key clinical studies submitted to the FDA in the last 10 years in support of potential marketing approval for prostate cancer (PCa) prevention or treatment.

Abiraterone acetate in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer: U.S. Food and Drug Administration drug approval summary.

On December 10, 2012, the U.S. Food and Drug Administration granted full approval for a modified indication for abiraterone acetate (Zytiga tablets; Janssen Biotech, Inc.

Targeting the regulation of androgen receptor signaling by the heat shock protein 90 cochaperone FKBP52 in prostate cancer cells.

Drugs that target novel surfaces on the androgen receptor (AR) and/or novel AR regulatory mechanisms are promising alternatives for the treatment of castrate-resistant prostate cancer. The 52 kDa FK506 binding protein (FKBP52) is an important positive regulator of AR in cellular and whole animal models and represents an attractive target for the treatment of prostate cancer. We used a modified receptor-mediated reporter assay in yeast to screen a diversified natural compound library for inhibitors of FKBP52-enhanced AR function.

Accelerated approval of oncology products: the food and drug administration experience.

We reviewed the regulatory history of the accelerated approval process and the US Food and Drug Administration (FDA) experience with accelerated approval of oncology products from its initiation in December 11, 1992, to July 1, 2010. The accelerated approval regulations allowed accelerated approval of products to treat serious or life-threatening diseases based on surrogate endpoints that are reasonably likely to predict clinical benefit. Failure to complete postapproval trials to confirm clinical benefit with due diligence could result in removal of the accelerated approval indication from the market.

Tumor regression and growth rates determined in five intramural NCI prostate cancer trials: the growth rate constant as an indicator of therapeutic efficacy.

Purpose: In solid tumors such as prostate cancer, novel paradigms are needed to assess therapeutic efficacy. We utilized a method estimating tumor growth and regression rate constants from serial PSA measurements, and assessed its potential in patients with metastatic castration resistant prostate carcinoma (mCRPC).

Experimental Design: Patients were enrolled in five phase II studies, including an experimental vaccine trial, representing the evolution of therapy in mCRPC.

Phase II trial of bevacizumab, thalidomide, docetaxel, and prednisone in patients with metastatic castration-resistant prostate cancer.

PURPOSE We previously demonstrated that thalidomide appears to add to the activity of docetaxel in metastatic castration-resistant prostate cancer (CRPC). Phase II studies combining docetaxel with bevacizumab have had substantial antitumor activity. We hypothesized that the combination of docetaxel plus these antiangiogenic drugs with different targets would have substantial clinical activity.

Reversal of docetaxel resistance with bevacizumab and thalidomide.

Taxane resistance is a common clinical problem in the treatment of many metastatic malignancies. Observational clues or evidence of overcoming such resistance is important for developing treatments that can extend taxane activity. We report a case of the reversal of docetaxel resistance with the addition of antiangiogenic agents bevacizumab and thalidomide to docetaxel and prednisone in a patient with metastatic castration-resistant prostate cancer after PSAWG progression on docetaxel and prednisone.

Higher incidence of Osteonecrosis of the Jaw (ONJ) in patients with metastatic castration resistant prostate cancer treated with anti-angiogenic agents.

ONJ is an important toxicity in cancer patients receiving bisphosphonate therapy. Here we report a higher than usual incidence of ONJ, 11 of 60 (18.3%, 95% Confidence Interval, CI: 9%-28%) patients enrolled in a phase II clinical trial combining bevacizumab, docetaxel, thalidomide, and prednisone (ATTP) in chemotherapy-naive men with metastatic castration resistant prostate cancer (mCRPC).

Liposomal doxorubicin in combination with bortezomib for relapsed or refractory multiple myeloma.

Purpose: On May 17, 2007, doxorubicin HCl liposome injection (Doxil) in combination with bortezomib (Velcade) received approval from the US Food and Drug Administration (FDA) for the treatment of relapsed or refractory multiple myeloma after at least one prior therapy that has not included bortezomib. Liposomal doxorubicin's efficacy and safety were demonstrated in a phase III, randomized, multicenter, international trial comparing the combination of this agent plus bortezomib vs bortezomib alone in multiple myeloma patients who had not previously received bortezomib and had received at least one prior therapy. Here we summarize the FDA review of the data that support this approval.