Breaking News
January 20, 2018 - MSU scientists seek to identify brain mechanisms related to psychosis
January 20, 2018 - Syndax Pharmaceuticals Announces Clinical Collaboration to Evaluate Entinostat in Combination with anti-PD-L1 Cancer Immunotherapy in Breast Cancer
January 20, 2018 - Endoscopes Over Microscopes in Retinal Surgery: Ophthalmology Times
January 20, 2018 - Technology not taking over children’s lives despite screen-time increase
January 20, 2018 - Study finds extensive contamination around lead battery recycling plants in 7 African countries
January 20, 2018 - Flu may pass to others through exhaled breath, study shows
January 20, 2018 - Neuronal loss very limited in Alzheimer’s disease, new study shows
January 20, 2018 - Novel robot can aid treatment of rare birth defect
January 19, 2018 - TherapeuticsMD Announces Submission of New Drug Application for TX-001HR
January 19, 2018 - Fighting Infant Mortality | Medpage Today
January 19, 2018 - Researchers offer new evidence on four-year-old children’s knowledge about ecology
January 19, 2018 - Analysis finds overlooked crucial factor in determining prognosis for DIPGs
January 19, 2018 - Review explores consequences of genetic testing and cancer risk-reducing surgery
January 19, 2018 - Morning Break: HHS Div. of Religious Freedom; Trump’s Heart Health; Minister of Loneliness
January 19, 2018 - Parkinson’s disease ‘jerking’ side effect detected by algorithm
January 19, 2018 - New analysis finds dramatic increases in maternal mortality rates
January 19, 2018 - Weight-Loss Surgery’s Benefits Wane Over Time for Diabetics
January 19, 2018 - Cath Lab Recap: Sapien 3 Delivery System Recall; Transatlantic PCI Smackdown
January 19, 2018 - Parkinson’s treatment could be more effective, student finds
January 19, 2018 - New vaccine approach offers effective protection against tuberculosis
January 19, 2018 - Home care agencies often wrongly deny Medicare help to the chronically ill
January 19, 2018 - One hundred percent fruit juice does not alter blood sugar levels
January 19, 2018 - Prebiotics could enhance learning and memory skills in infants
January 19, 2018 - CMS May Cover MRI With Cardiac Devices Across the Board
January 19, 2018 - As income rises, women get slimmer—but not men
January 19, 2018 - Researchers develop adhesive materials to prevent bracket stains on teeth
January 19, 2018 - Flu can be spread without coughs and sneezes
January 19, 2018 - AMSBIO’s new recombinant protein shows great promise for organoid culture
January 19, 2018 - AbbVie’s Upadacitinib Granted Breakthrough Therapy Designation from the U.S. Food and Drug Administration for Atopic Dermatitis
January 19, 2018 - ASH: Pomalidomide Dose Escalation Improves Response
January 19, 2018 - Is your child’s school an obesity risk?
January 19, 2018 - Scientists describe groundbreaking training effect on the innate immune system
January 19, 2018 - MAST announces new AmpC, ESBL & Carbapenemase Detection Set
January 19, 2018 - Signaling molecules likely involved in concussions, rodent studies show
January 19, 2018 - Mast introduces Carba plus for CPE and OXA-48 confirmation
January 19, 2018 - Paleolithic diet helps overweight women maintain weight loss
January 19, 2018 - Agios Submits New Drug Application to the FDA for Ivosidenib for the Treatment of Patients with Relapsed/Refractory AML and an IDH1 Mutation
January 19, 2018 - This Flu Season, Don’t Forget About Tamiflu
January 19, 2018 - Amsterdam wins battle to host EU medicines agency after Brexit
January 19, 2018 - Study suggests movement as accurate method to diagnose neurodevelopmental disorders
January 19, 2018 - Maximize resolution in deep imaging for neuroscience research with Olympus TruResolution objectives
January 19, 2018 - Bilingualism may benefit children with ASD
January 19, 2018 - FDA Alert: Levofloxacin in 5 Percent Dextrose 250mg/50mL by AuroMedics: Recall
January 19, 2018 - USPSTF Not Backing Ankle-Brachial Index, CRP, or Coronary Calcium
January 19, 2018 - Higher omega-3 fatty acid intake tied to lower glaucoma risk
January 19, 2018 - Findings reveal conventional cancer therapy as double-edged sword
January 19, 2018 - Health Highlights: Jan. 16, 2018
January 19, 2018 - Morning Break: Anti-Emetic Warning; Uninsured Rate Jumps; Flu Worsens Saline Shortage
January 19, 2018 - Increased use of ambulatory surgery centers for cataract surgery
January 19, 2018 - Not-for-profit hospitals coming up with their own generic medicines to combat shortages
January 19, 2018 - $500 cancer detection blood tests may soon become reality
January 19, 2018 - Chronic traumatic encephalopathy may start early even without signs of concussions
January 19, 2018 - Warm-up program for children cuts soccer injuries by 50%
January 19, 2018 - ‘You’re Old and You Need Tests’: What We Heard This Week
January 19, 2018 - Egg-preserving hysterectomy raises heart risks later: study
January 19, 2018 - GA-map Dysbiosis Test identifies IBS patients who respond to FODMAP diet, study shows
January 19, 2018 - Study explores mortality and health-related habits in former elite athletes and their brothers
January 19, 2018 - New biodegradable sensors could assist doctors
January 19, 2018 - Modular gene enhancers may be suitable target in treatment of blood cancer
January 18, 2018 - New precision medicine trial for metastatic pancreatic cancer
January 18, 2018 - Shire Receives FDA Breakthrough Therapy Designation for Maribavir, an Investigational Treatment for Cytomegalovirus (CMV) Infection in Transplant Patients
January 18, 2018 - Pre-Existing Patient-Valve Mismatch Trips Up ViV Implant
January 18, 2018 - Adolescents: health risks and solutions
January 18, 2018 - US woman delivers baby from embryo frozen for 24 years
January 18, 2018 - Study identifies new target for treatment of depression
January 18, 2018 - LJI study reveals key player that promotes skin inflammation in atopic dermatitis
January 18, 2018 - Study devises efficient and economical strategy to screen breast and ovarian cancer gene mutations
January 18, 2018 - Agile Therapeutics, Inc. Receives a Complete Response Letter from the FDA for Twirla (AG200-15) for the Prevention of Pregnancy
January 18, 2018 - Gene Therapy for Inherited Retinal Dystrophy Gets FDA Clearance
January 18, 2018 - Researchers identify a new chemical pathway that helps the brain detect sweet, savory and bitter flavors
January 18, 2018 - IBV develops platform that helps companies to diagnose wellbeing of their workforce
January 18, 2018 - Study to test new precision medicine approach for metastatic pancreatic cancer
January 18, 2018 - World’s first vaccine relieves grass pollen allergy symptoms by at least 25%, study shows
January 18, 2018 - FDA Approves New Indication for Gilotrif (afatinib) in EGFR Mutation-Positive NSCLC
January 18, 2018 - Oncologists Dish on Top Issues for 2018
January 18, 2018 - Researchers identify new potential drug target for Huntington’s disease
January 18, 2018 - Metrohm USA welcomes employees to new headquarters in Florida
January 18, 2018 - Human waste remains main source of fecal pollution in the river Danube
January 18, 2018 - Expert discusses how to stay healthy during flu season
January 18, 2018 - New biomaterials-based system improves T-cell production
Tumor Cell Test Tops PSA for Survival in mCRPC

Tumor Cell Test Tops PSA for Survival in mCRPC

image_pdfDownload PDFimage_print

Action Points

  • Note that this analysis of data from 5 trials suggests that absence of circulating tumor cells performs better as a biomarker than change in PSA in terms of assessing response to therapy in metastatic, castration-resistant prostate cancer.
  • Be aware that the performance of this biomarker in clinical practice may be different than its performance in the context of a clinical trial.

Absence of circulating tumor cells (CTCs) after 13 weeks of treatment outperformed other potential markers of improved survival in patients with metastatic castration-resistant prostate cancer (mCRPC), a retrospective analysis of five randomized trials showed.

A decline in CTCs from nonzero at baseline to 0 at 13 weeks (CTC0) had a discriminatory power of 0.81 for predicting improved survival versus patients who did not achieve CTC0 status. The FDA-cleared response measure of CTC conversion (≥5 at baseline, ≤4 at 13 weeks) followed with a discriminatory power of 0.79. However, substantially more patients were evaluable for CTC0 than CTC conversion.

Six other response endpoints (CTC and PSA values) had discriminatory power ranging from 0.71 to 0.79, as reported online in the Journal of Clinical Oncology.

“The CTC0 endpoint is an indicator that cancer cells that were circulating in the blood are no longer detectable, an easily recognized outcome that is clinically meaningful to patients,” . “It is an outcome that occurs shortly after treatment initiation, providing researchers and practitioners with objective and reliable evidence that the therapy being administered had altered the patient’s prognosis in a favorable way.

“Taken together, the results of this study support the use of CTC0 as a response endpoint in early-phase clinical trials.”

The author of an accompanying editorial said that “the unambiguous interpretation of a positive and negative [CTC0] test should make this early efficacy marker an attractive intermediate endpoint for consideration of accelerated drug approval by regulatory bodies.”

“However, whether this endpoint should be used in routine clinical practice outside of a clinical trial (ie., as a measure of clinical benefit itself) is far less certain and seems premature at this time,” wrote Emanuel Antonarakis, MD, of Johns Hopkins University in Baltimore.

Antonarakis also acknowledged that PSA-based endpoints had less discriminatory power for predicting overall survival but pointed out that they could be evaluated in almost all patients across the five trials included in the analysis.

The need for clinically meaningful measures of response that occur early in the course of treatment for mCRPC has increased with the expansion of treatment options, including six new agents with diverse mechanisms of action approved since 2010. Each therapy’s approval was based on demonstration of a survival benefit in a large phase III trial, Scher and co-authors noted in their introduction.

In parallel with therapeutic expansion, advances in molecular profiling increased clinicians’ ability to identify subsets of patients and determine their likelihood of response to a given therapy. Historically, PSA-based tests were used to assess treatment efficacy, although the assessments did not provide a strong indication of survival, the authors continued.

In studies of mCRPC, patients with bone disease had higher numbers of CTCs compared with patients who have lymph node involvement, suggesting an association with metastatic spread. Inhibiting the spread of CTCs, therefore, should represent a clinically meaningful therapeutic objective, the authors continued. After phase II studies of abiraterone (Zytiga) and enzalutamide (Xtandi) showed CTC conversion rates of 30-40%, a research collaboration was formed in association with the FDA to study post-treatment CTC-based endpoints in phase III clinical trials.

Scher and colleagues reported findings from an analysis of short-term changes in CTC and PSA and their association with overall survival. The analysis comprised 6,081 patients with mCRPC from five prospective, randomized, phase III trials. Investigators examined the discriminatory power of CTC0 and CTC conversion at 13 weeks for identifying patients who would have improved survival. They also evaluated the endpoints of 30%, 50%, and 70% decreases in CTC count, as well as 30%, 50%, and 70% decreases in PSA level at 13 weeks.

To determine the discriminatory strength of each endpoint, investigators used assessment of the weighted c-index, which has a range of 0.5 to 1.0. A value of 0.5 reflected no discriminatory power between response and nonresponse, and a value of 1.0 indicated that almost all non-responding patients died before responding patients with the shortest survival. The analysis yielded the following discriminatory values:

  • CTC0: 0.81
  • CTC conversion: 0.79
  • CTC30: 0.72
  • CTC50: 0.72
  • CTC70: 0.73
  • PSA30: 0.71
  • PSA50: 0.72
  • PSA70: 0.74

The authors found that 75% of the patients could be evaluated for CTC0 compared with 51% for CTC conversion. As compared with a 70% decrease in PSA at 13 weeks, CTC0 offered significantly better discriminatory power (P=0.026) and, by extension, significantly better discrimination compared with PSA30 and PSA50.

“In addition to greater discrimination, the CTC0 and CTC conversion response endpoints were more robust, producing consistent weighted c-indices across the five trials,” the authors noted.

This work was partially supported by the FDA as part of a program to develop intermediate endpoints in castration-resistant prostate cancer. Some co-authors were employees of firms with commercial interests in such biomarkers.

Scher disclosed relationships with Asterias Biotherapeutics, Ferring Pharmaceuticals, WIRB-Copernicus Group, Merck, Clovis Oncology, Janssen Research & Development, Astellas Pharma, Sanofi, Physician’s Education Resource, OncLive Insights, Innocrin Pharmaceuticals, and Illumina.

Antonarakis disclosed relationships with Sanofi, Dendreon, Medivation, Janssen Biotech, ESSA, Astellas Pharma, Johnson & Johnson, Aragon Pharmaceuticals, Exelixis, Millennium, Genentech, Novartis, Tokai Pharmaceuticals, and patent/royalty/intellectual property interest.

  • Reviewed by
    F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner

2018-01-10T15:30:00-0500

Tagged with:

About author

Related Articles