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Background: Recent observations suggest that prostate cancer is an increasing disease among older adolescents and young adults.Methods: Incidence, mortality, and survival data were obtained from the US National Cancer Institute Surveillance, Epidemiology, and End Results program and the Institute for Health Metrics and Evaluation Global Burden of Disease database.Results: Worldwide, the incidence of prostate cancer has increased in all groups between ages 15 and 40 years and increased globally at a steady rate averaging 2% per year since 1990 (P < .01). In the United States, this age group was >6 times more likely than older men to have distant disease at diagnosis. Stage for stage, their survival rate improved less than in older men. Whereas the overall 5-year relative survival rate in the United States for men diagnosed between ages 40 and 80 years was between 95% and 100%, it was 30% in those aged 15 to 24 years, 50% in those aged 20 to 29 years, and 80% in those aged 25 to 34 years.Conclusions: Prostate cancer in older adolescent and young adult men has increased in most countries. There is some evidence that this may be caused in part by underdiagnosis, prostate-specific antigen screening, and overdiagnosis. It also may be caused by trends in obesity, physical inactivity, HPV infection, substance exposure, environmental carcinogens, and/or referral patterns. How the biology of these cancers differs from that in older men and how the etiologies vary from country to country remain to be determined. [ABSTRACT FROM AUTHOR]

Background Activation of the vascular endothelial growth factor receptor (VEGFR) and the oncogenic Src pathway has been implicated in the development of castration-resistant prostate cancer (CRPC) in preclinical models. Cediranib and dasatinib are multi-kinase inhibitors targeting VEGFR and Src respectively. Phase II studies of cediranib and dasatinib in CRPC have shown single agent activity. Methods Docetaxel-pretreated CRPC patients were randomized to arm A: cediranib alone (20 mg/day) versus arm B: cediranib (20 mg/day) plus dasatinib (100 mg/day) given orally on 4-week cycles. Primary endpoint was 12-week progression-free survival (PFS) as per the Prostate Cancer Clinical Trials Working Group (PCWG2). Patient reported outcomes were evaluated using Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Present Pain Intensity (PPI) scales. Correlative studies of bone turnover markers (BTM), including bone alkaline phosphate (BAP) and serum beta-C telopeptide (B-CTx) were serially assayed. Results A total of 22 patients, 11 per arm, were enrolled. Baseline demographics were similar in both arms. Median number of cycles =4 in arm A (range 1-12) and 2 in arm B (range 1-9). Twelve-week PFS was 73 % in arm A versus 18 % in arm B ( p = 0.03). Median PFS in months (arm A versus B) was: 5.2 versus 2.6 (95 % CI: 1.9-6.5 versus 1.4-not reached). Most common grade 3 toxicities were hypertension, anemia and thrombocytopenia in arm A and hypertension, diarrhea and fatigue in arm B. One treatment-related death (retroperitoneal hemorrhage) was seen in arm A. FACT-P and PPI scores did not significantly change in either arm. No correlation between BTM and PFS was seen in either arm. Conclusions Although limited by small numbers, this randomized study showed that the combination of VEGFR and Src targeted therapy did not result in improved efficacy and may be associated with a worse outcome than VEGFR targeted therapy alone in patients with CRPC. ClinicalTrials.gov number: NCT01260688. [ABSTRACT FROM AUTHOR]

Purpose: Non-V600 mutations comprise approximately 35% of all BRAF mutations in cancer. Many of these mutations have been identified as oncogenic drivers and can be classified into three classes according to molecular characteristics. Consensus treatment strategies for class 2 and 3 BRAF mutations have not yet been established., Methods: We performed a systematic review and meta-analysis with published reports of individual patients with cancer harboring class 2 or 3 BRAF mutations from 2010 to 2021, to assess treatment outcomes with US Food and Drug Administration-approved mitogen-activated protein kinase (MAPK) pathway targeted therapy (MAPK TT) according to BRAF class, cancer type, and MAPK TT type. Coprimary outcomes were response rate and progression-free survival., Results: A total of 18,167 studies were screened, identifying 80 studies with 238 patients who met inclusion criteria. This included 167 patients with class 2 and 71 patients with class 3 BRAF mutations. Overall, 77 patients achieved a treatment response. In both univariate and multivariable analyses, response rate and progression-free survival were higher among patients with class 2 compared with class 3 mutations, findings that remain when analyses are restricted to patients with melanoma or lung primary cancers. MEK ± BRAF inhibitors demonstrated greater clinical activity in class 2 compared with class 3 BRAF-mutant tumors than BRAF or EGFR inhibitors., Conclusion: This meta-analysis suggests that MAPK TTs have clinical activity in some class 2 and 3 BRAF-mutant cancers. BRAF class may dictate responsiveness to current and emerging treatment strategies, particularly in melanoma and lung cancers. Together, this analysis provides clinical validation of predictions made on the basis of a mutation classification system established in the preclinical literature. Further evaluation with prospective clinical trials is needed for this population., Competing Interests: Benny JohnsonConsulting or Advisory Role: Gritstone Bio, Incyte, Taiho Oncology, InsmedResearch Funding: Bristol Myers Squibb (Inst), Syntrix Biosystems (Inst) Ibiayi Dagogo-JackHonoraria: American Academic Health System, Total Health Conferencing, DAVA Oncology, Creative Educational Concepts, Medscape, ASCO Post, OncLive/MJH Life SciencesConsulting or Advisory Role: Boehringer Ingelheim, AstraZeneca, Xcovery, Catalyst Pharmaceuticals, Pfizer, Syros Pharmaceuticals, Novocure, BostonGene, Bayer, Genentech, Sanofi, JanssenResearch Funding: Pfizer (Inst), Array BioPharma (Inst), Novartis (Inst), Genentech (Inst), Calithera Biosciences (Inst), Vivace Therapeutics (Inst)Travel, Accommodations, Expenses: Pfizer, Array BioPharma Nathaniel J. MyallHonoraria: Patient Power Georg RichtigTravel, Accommodations, Expenses: Ipsen Marco GerlingerStock and Other Ownership Interests: VertexResearch Funding: Bristol Myers Squibb, Merck KGaA, Roche/Genentech Eiji ShinozakiHonoraria: Yakult Honsha, Merck Serono, Chugai Pharma, Takeda, Sanofi, Lilly, Taiho Pharmaceutical, Daiichi Sankyo/UCB Japan Takayuki YoshinoHonoraria: Chugai Pharma, Merck, Bayer Yakuhin, Ono Pharmaceutical, MSD K.K.Research Funding: MSD (Inst), Daiichi Sankyo Company, Limited (Inst), Ono Pharmaceutical (Inst), Taiho Pharmaceutical (Inst), Amgen (Inst), Sanofi (Inst), Pfizer (Inst), Genomedia (Inst), Sysmex (Inst), Nippon Boehringer Ingelheim (Inst), Chugai Pharma (Inst) Daisuke KotaniHonoraria: Takeda, Chugai Pharma, Lilly Japan, Merck Serono, Sysmex, Taiho Pharmaceutical, Ono Pharmaceutical, Bristol Myers Squibb Japan, MSD, Daiichi Sankyo/UCB JapanResearch Funding: Ono Pharmaceutical (Inst), MSD (Inst), Novartis (Inst), Janssen (Inst), IQvia (Inst), Syneos Health (Inst), CMIC (Inst) Jason R. FangusaroHonoraria: AstraZeneca, Pyramid BiosciencesConsulting or Advisory Role: Celgene, AstraZeneca Oliver GautschiConsulting or Advisory Role: Amgen (Inst), Lilly (Inst)Other Relationship: Bayer (Inst), Pfizer (Inst), Roche (Inst), Merck, Lilly Julien MazieresConsulting or Advisory Role: Novartis, Roche/Genentech, Pfizer, Bristol Myers Squibb, Lilly/ImClone, MSD, AstraZeneca, Pierre Fabre, Blueprint Medicines, Hengrui TherapeuticsResearch Funding: Roche (Inst), Bristol Myers Squibb (Inst), AstraZeneca (Inst), Pierre Fabre (Inst)Travel, Accommodations, Expenses: Pfizer, Roche, Bristol Myers Squibb Jeffrey A. SosmanHonoraria: Jazz Pharmaceuticals, Apexian Pharmaceuticals, Iovance BiotherapeuticsConsulting or Advisory Role: Apexigen, Jazz Pharmaceuticals, Iovance Biotherapeutics Scott KopetzThis author is a member of the JCO Precision Oncology Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript.Stock and Other Ownership Interests: MolecularMatch, Lutris, Iylon, Frontier MedicinesConsulting or Advisory Role: Genentech, EMD Serono, Merck, Holy Stone Healthcare, Novartis, Lilly, Boehringer Ingelheim, Boston Biomedical, AstraZeneca/MedImmune, Bayer Health, Pierre Fabre, Redx Pharma, Ipsen, Daiichi Sankyo, Natera, HalioDx, Lutris, Jacobio, Pfizer, Repare Therapeutics, Inivata, GlaxoSmithKline, Jazz Pharmaceuticals, Iylon, Xilis, AbbVie, Amal Therapeutics, Gilead Sciences, Mirati Therapeutics, Flame Biosciences, Servier, Carina Biotech, Bicara Therapeutics, Endeavor BioMedicines, Numab, Johnson & Johnson/Janssen, Genomic Health, Frontier Medicines, Replimune, Taiho PharmaceuticalResearch Funding: Sanofi, Biocartis, Guardant Health, Array BioPharma, Genentech/Roche, EMD Serono, MedImmune, Novartis, Amgen, Lilly, Daiichi Sankyo Vivek SubbiahConsulting or Advisory Role: MedImmune, Helsinn Therapeutics, Loxo, R-Pharm, QED TherapeuticsResearch Funding: Novartis (Inst), GlaxoSmithKline (Inst), NanoCarrier (Inst), Northwest Biotherapeutics (Inst), Genentech/Roche (Inst), Berg Pharma (Inst), Bayer (Inst), Incyte (Inst), Fujifilm (Inst), PharmaMar (Inst), D3 Oncology Solutions (Inst), Pfizer (Inst), Amgen (Inst), AbbVie (Inst), Multivir (Inst), Blueprint Medicines (Inst), LOXO (Inst), Vegenics (Inst), Takeda (Inst), Alfasigma (Inst), Agensys (Inst), Idera (Inst), Boston Biomedical (Inst), Inhibrx (Inst), Exelixis (Inst), Turning Point Therapeutics (Inst)Travel, Accommodations, Expenses: PharmaMar, Bayer, Novartis, Helsinn TherapeuticsOther Relationship: Medscape Michael A. DaviesConsulting or Advisory Role: Genentech/Roche, Novartis, Bristol Myers Squibb, NanoString Technologies, Array BioPharma, Apexigen, Pfizer, Eisai, ABM, Iovance BiotherapeuticsResearch Funding: GlaxoSmithKline (Inst), Genentech/Roche (Inst), AstraZeneca (Inst), Merck (Inst), Oncothyreon (Inst), Myriad Genetics (Inst), Sanofi (Inst), Pfizer (Inst), ABM (Inst), LEAD (Inst) Anna L. GrooverEmployment: BioMed Valley Discoveries Ryan J. SullivanConsulting or Advisory Role: Novartis, Merck, Replimune, Asana Biosciences, Alkermes, Eisai, Pfizer, Iovance Biotherapeutics, OncoSec, AstraZeneca, Bristol Myers SquibbResearch Funding: Amgen (Inst), Lilly (Inst), BioMed Valley Discoveries (Inst), Merck (Inst), Deciphera (Inst), Roche/Genentech (Inst), Moderna Therapeutics (Inst), Sanofi (Inst), Aeglea Biotherapeutics (Inst), Asana Biosciences (Inst), Viralytics (Inst), Compugen (Inst), Neon Therapeutics (Inst), Pfizer (Inst), BeiGene (Inst), Rubius Therapeutics (Inst), Strategia (Inst) Keith T. FlahertyStock and Other Ownership Interests: Clovis Oncology, Loxo, X4 Pharma, Strata Oncology, PIC Therapeutics, Apricity Health, Oncoceutics, FOGPharma, Tvardi Therapeutics, Checkmate Pharmaceuticals, Kinnate Biopharma, Scorpion Therapeutics, ALX Oncology, xCures, Monopteros Therapeutics, Vibliome Therapeutics, Transcode Therapeutics, Soley Therapeutics, Nextech InvestConsulting or Advisory Role: Novartis, Lilly, Oncoceutics, Tvardi Therapeutics, Takeda, Debiopharm Group, OmRx Douglas B. JohnsonConsulting or Advisory Role: Bristol Myers Squibb, Merck, Novartis, Iovance Biotherapeutics, Catalyst Pharmaceuticals, Oncosec, Pfizer, Mosaic ImmunoEngineering, Targovax, MallinckrodtResearch Funding: Incyte, Bristol Myers SquibbPatents, Royalties, Other Intellectual Property: Intellectual property and patents pending surrounding use of MHC-II and response to immune therapy David W. CesconConsulting or Advisory Role: Pfizer, AstraZeneca, Novartis, GlaxoSmithKline, Merck, Roche/Genentech, Exact Sciences, Gilead Sciences, EisaiResearch Funding: Merck (Inst), Roche/Genentech (Inst), GlaxoSmithKline (Inst), Pfizer (Inst), Inivata (Inst), AstraZeneca (Inst), Gilead Sciences (Inst)Patents, Royalties, Other Intellectual Property: Patent (US62/675,228) for methods of treating cancers characterized by a high expression level of spindle and kinetochore-associated complex subunit 3 (ska3) geneUncompensated Relationships: Inivata Anna SpreaficoHonoraria: Bristol Myers Squibb, Medison & ImmunocoreConsulting or Advisory Role: Novartis, Merck, Bristol Myers Squibb, Oncorus, Medison & ImmunocoreResearch Funding: Bristol Myers Squibb, Novartis, Merck, Symphogen, AstraZeneca/MedImmune, Bayer, Surface Oncology, Janssen Oncology, Northern Biologics, Replimune, Roche, Alkermes, Array BioPharma, GlaxoSmithKline, Treadwell Therapeutics (Inst), Amgen (Inst)Travel, Accommodations, Expenses: Merck, Bristol Myers Squibb, Idera, Bayer, Janssen Oncology, Roche George ZogopoulosPatents, Royalties, Other Intellectual Property: TC-PTP inhibitors as APC activators for immunotherapyTravel, Accommodations, Expenses: Baxalta April A.N. RoseEmployment: Merck (I)Stock and Other Ownership Interests: Merck (I)Consulting or Advisory Role: PfizerNo other potential conflicts of interest were reported.

The patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) complements capture of symptomatic adverse events (AEs) by clinicians. Previous trials have typically used a limited subset of relevant symptomatic AEs to reduce patient burden. We aimed to determine the feasibility of administering all 80 AEs included in the PRO-CTCAE library by approaching consecutive patients enrolled in a large academic phase I program at three points in time. Here, we report a preplanned analysis after enrolling the first 20 patients. All items were answered on 51 of 56 potential visits (adherence 91%). Three (5%) additional PRO-CTCAE assessments were partially completed, and two (4%) were missed because of conflicting appointments. No patient withdrew consent or chose not to complete the assessments once enrolled on study. Future trials of experimental drugs that incorporate the PRO-CTCAE should consider using this unselected approach to identify adverse events more completely., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2019.)