Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. Is Your Fear of A Cancer Diagnosis Keeping You Away from the Doctor? Target Audience: This activity is designed to meet the educational needs of oncologists, nurses, pharmacists, and other healthcare professionals who manage patients with cancer. Sandy Srinivas, MD, Panel Vice Chair, has disclosed that she is a scientific advisor for Bayer HealthCare, and receives grant/research support from Bayer HealthCare, Endocyte, and Exelixis Inc. Emmanuel S. Antonarakis, MD, Panel Member, has disclosed that he has received consulting fees from Amgen Inc., Astellas Pharma US, Inc., AstraZeneca Pharmaceuticals LP, Clovis Oncology, Dendreon Corporation, Eli Lilly and Company, GlaxoSmithKline, Janssen PharmaceuticaProducts, LP, Medivation, Inc., Merck & Co., Inc., and ESSA Pharma, Inc.; received grant/research support from AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb Company, Celgene Corporation, Clovis Oncology, Dendreon Corporation, Genentech, Inc., Janssen PharmaceuticaProducts, LP, Johnson & Johnson, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Tokai, and sanofi-aventis U.S.; and receives royalty income from Qiagen. JAMA Oncol 2019;5:471â478. Horsham, PA: Janssen Products, LP; 2019. Only a couple of weeks after Rubraca (rucaparib) was approved for the treatment of prostate cancer, the National Comprehensive Cancer Network (NCCN) has updated its guidelines recommending this PARP inhibitor as an option for select prostate cancer patients in the U.S.. Treatment options for patients with mCRPC are based mainly on prior treatment exposure, namely to docetaxel and novel hormone therapies that are now often administered in earlier stages of disease. The panel discussed that, as these hormone therapies began to be used in earlier settings, it became less clear what treatments are appropriate in the mCRPC setting. Loriot Y, Bianchini D, Ileana E, . 2. However, other clinical-grade somatic or germline DNA sequencing assays that include the BRCA1/2 genes, including germline and somatic tumor tissue and cell-free DNA, can also be used for patient selection. Nonmetastatic, castration-resistant prostate cancer and survival with darolutamide. J Clin Oncol 2019;37:1120â1129. Castration-resistant prostate cancer (CRPC) is prostate cancer that progresses clinically, radiographically, or biochemically despite castrate levels of serum testosterone (<50 ng/dL). NCCN Guidelines with Evidence Blocks - Chronic Lymphocytic … It was approved in this setting in February of 2018, based on 2 trials that demonstrated improved OS over ADT alone.18â20. The primary endpoint of ORR in cohorts 1 and 2 was 5% (95% CI, 2%â11%) and 3% (95% CI, <1%â11%), respectively. Ann Oncol 2013;24:1807â1812. Hussain M, Fizazi K, Saad F, . The NCCN Guidelines for Prostate Cancer address staging and risk assessment after a prostate cancer diagnosis and include management options for localized, regional, and metastatic disease. Clinical activity of abiraterone acetate in patients with metastatic castration-resistant prostate cancer progressing after enzalutamide. Bianchini D, Lorente D, Rodriguez-Vida A, . Enzalutamide [package insert]. Fizazi K, Kramer G, Eymard JC, . Pancreatic Adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. Release date: February 10, 2021; Expiration date: February 10, 2022. Growth factor support should be used. Nature 2005;434:917â921. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment. Deborah A. Freedman-Cass, PhD, Manager, Licensed Clinical Content, NCCN, has disclosed that she has no relevant financial relationships. Darolutamide in nonmetastatic, castration-resistant prostate cancer. Cell 2015;161:1215â1228. Le DT, Durham JN, Smith KN, . Abiraterone + dexamethasone was well tolerated in this study, with no grade 3/4 toxicity reported, and no dose reduction required. Most men with advanced disease eventually stop experiencing a response to traditional ADT and are categorized as castration-resistant. Davis ID, Martin AJ, Stockler MR, . Participation in clinical trials is especially encouraged. © National Comprehensive Cancer Network, Inc. 2021. Olaparib for metastatic castration-resistant prostate cancer. Prospective multicenter validation of androgen receptor splice variant 7 and hormone therapy resistance in high-risk castration-resistant prostate cancer: the PROPHECY study. Optimal sequencing of systemic therapies for patients with mCRPC remains challenging, but newer data have helped to support patients and clinicians as they make decisions for first, second, and subsequent lines of therapy in the CRPC setting. JAMA Oncol 2019;5:1159â1167. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. Any commercially available analytically and clinically validated somatic tumor and circulating tumor DNA (ctDNA) assays and germline assays can be used to identify patients for treatment. The list of systemic therapy options for patients with mCRPC has expanded in recent years, with several additions made to the 1.2021 version of the NCCN Guidelines. Pembrolizumab for treatment-refractory metastatic castration-resistant prostate cancer: multicohort, open-label phase II KEYNOTE-199 study. N Engl J Med 2019;381:13â24. Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate. Enzalutamide and survival in nonmetastatic, castration-resistant prostate cancer. The portions of the guidelines includ … … This activity is supported by an independent educational grant from AbbVie. Disease progression on abiraterone or enzalutamide had to have occurred within 12 months for patients to be eligible. Specific options, as delineated in the guidelines for patients with and without distant metastases, are based on a large body of data. J Clin Oncol 2008;26:1148â1159. Annual report to the nation on the status of cancer, 1975-2011, featuring incidence of breast cancer subtypes by race/ethnicity, poverty, and state. Science 2017;357:409â413. Instead of organizing the choices as lines of therapy, they included 4 groups of treatments based on prior therapeutic exposures: no prior docetaxel/no prior novel hormone therapy; prior novel hormone therapy/no prior docetaxel; prior docetaxel/no prior novel hormone therapy; and prior docetaxel/prior novel hormone therapy (see PROS-16, page 136). Antitumour activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100). A randomized, open-label, phase I/II trial sought to determine the maximum tolerated dose and investigator-assessed PFS with combination cabazitaxel + carboplatin in patients with mCRPC.56 In the phase II part of the trial, 160 patients were randomized to 25 mg/m2 cabazitaxel or 25 mg/m2 cabazitaxel + carboplatin at area under the curve (AUC) 4 mg/mL/min. The pilot single-arm, open-label, phase II SWITCH study evaluated the efficacy of abiraterone with 0.5 mg dexamethasone daily in 26 patients with mCRPC who experienced disease progression on abiraterone with 5 mg prednisone twice daily.57 The primary endpoint was the proportion of patients achieving a PSA decline of â¥30% after 6 weeks on abiraterone with dexamethasone, and 46.2% of participants met this criteria. Preliminary clinical data on olaparib suggested favorable activity of this agent in patients with HRR gene mutations, but not in those without.45,46,50 The phase III PROfound study was a randomized trial evaluating olaparib at 300 mg twice daily versus physicianâs choice of abiraterone or enzalutamide in patients with mCRPC and disease progression on at least one novel hormonal agent (abiraterone or enzalutamide) and up to one prior taxane agent (permitted but not required).51 Notably, 20% of patients had received both prior abiraterone and enzalutamide and were thus given agents on which they previously experienced progression. Results of early studies suggest that germline and somatic mutations in homologous recombination repair (HRR) genes (eg, BRCA1, BRCA2, ATM, PALB2, FANCA, RAD51D, CHEK2) may be predictive of the clinical benefit of PARP inhibitors.44â46 PARP inhibitors are oral agents that exert their activity through synthetic lethality.47 Currently, 2 PARP inhibitors, olaparib and rucaparib, are FDA-approved for use in prostate cancer.48,49 The panel discussed the FDA approvals and the data outlined below and voted to add olaparib and rucaparib to the guidelines in recent versions. Cardiovascular disease is the leading cause of death in men with prostate cancer.1. N Engl J Med 2020;383:2345â2357. Responses were durable (range, 1.9 to â¥21.8 months). The panel noted that patients with PPP2R2A mutations in the PROfound trial experienced an unfavorable risk/benefit profile; therefore, olaparib is not recommended in patients with PPP2R2A mutations. The 2020 NCCN Guidelines for metastatic castration-resistant prostate cancer incorporate hormonal agents (abiraterone acetate, enzalutamide), immunotherapies (sipuleucel-T, pembrolizumab for MSI-high tumors), cytotoxic agents (docetaxel, cabazitaxel), and DNA-damaging agents (radium-223). N Engl J Med 2017;377:352â360. Pembrolizumab for advanced prostate adenocarcinoma: findings of the KEYNOTE-028 study. The most common grade 3â5 adverse effects with cabazitaxel + carboplatin versus cabazitaxel alone were fatigue (20% vs 9%), anemia (23% vs 4%), neutropenia (16% vs 4%), and thrombocytopenia (14% vs 1%). The investigators focused on 4,654 Black men, at a mean age of 51.8 years, who were diagnosed with prostate cancer within the Veterans Health Administration. Clinical trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Rare but serious adverse effects include a theoretical risk of myelodysplasia or acute myeloid leukemia, and fetal teratogenicity.53,54. Careful monitoring of CBC counts and hepatic and renal function, along with type and screens and potential transfusion support and/or dose reductions as needed for severe anemia or intolerance are recommended during olaparib therapy. Share In a nutshell This study reviewed the current NCCN guidelines for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). … Annual County Resident Population Estimates … In that open-label single-arm phase II trial, patients with mCRPC harboring a deleterious or suspected deleterious germline or somatic BRCA1 or BRCA2 mutation and who had previously received therapy with a novel hormonal agent plus one taxane chemotherapy were treated with rucaparib at 600 mg twice daily.53 The primary endpoint of TRITON2 was ORR in patients with measurable disease, and was 43.5% (95% CI, 31.0%â56.7%) in this BRCA1/2-mutated population. This activity is supported by an independent medical educational grant from Mylan Inc. The section for initial prostate cancer diagnosis was extensively revised to include recommendations regarding germline genetic testing. CA Cancer J Clin 2020;70:7â30. Median radiographic PFS, a key secondary endpoint, was 9.0 months (95% CI, 8.3â13.5 months).53 The TRITON2 investigators have also reported outcomes for patients with non-BRCA1/2 mutations, and, similar to the PROfound trial, observed minimal to no responses in patients with ATM and CDK12 mutations.54, Adverse effects that may occur with rucaparib include anemia (including that requiring transfusion), fatigue, asthenia, nausea or vomiting, anorexia, weight loss, diarrhea or constipation, thrombocytopenia, creatinine elevation, increased liver transaminases, and rash. Upon completion of this activity, participants will be able to: The NCCN staff listed below discloses no relevant financial relationships: Kerrin M. Rosenthal, MA; Kimberly Callan, MS; Genevieve Emberger Hartzman, MA; Erin Hesler; Kristina M. Gregory, RN, MSN, OCN; Rashmi Kumar, PhD; Karen Kanefield; and Kathy Smith. Pharmacists: You must complete the posttest and evaluation within 30 days of the activity. Kohler BA, Sherman RL, Howlader N, . The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Survivorship provide screening, evaluation, and treatment recommendations for consequences of cancer and cancer treatment to aid healthcare professionals who work with survivors of adult-onset cancer. NCCN Guidelines with Evidence Blocks - Breast Cancer Version 4.2021.
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