title: Patients with Advanced Non-Small Cell Lung Cancer: Are Research Biopsies a Barrier to Participation in Clinical Trials?
abstract: OBJECTIVE
  Clinical trials of therapies for non-small cell lung cancer (NSCLC) are increasingly requiring mandatory tumor samples or research biopsies, both of which are potential barriers to trial participation. We assessed the impact of performance of research biopsies on the enrollment of patients with advanced NSCLC in clinical trials.
  
  
  METHODS
  The cases of patients with advanced NSCLC who had been evaluated for clinical trials of systemic therapy at the Princess Margaret Cancer Centre from January 2007 to March 2015 were reviewed.
  
  
  RESULTS
  Of the 55 clinical trials identified, 38 required tumor samples for enrollment. Six mandated repeat biopsies, whereas 32 permitted use of archival samples. Trial participation was offered to 636 patients at 940 unique study encounters, with some patients enrolling in multiple trials. Of the patients in 549 encounters during which participation in a therapeutic trial was offered, 60% received study treatment. More patients received study treatment (83% versus 55%, p < 0.0001) and study treatment was started earlier (after 9 days versus after 16, p = 0.002) when the trial did not have a mandatory tissue sample requirement. A similar trend was noted for trials permitting use of archival tissue versus mandatory repeat biopsies. The most common barriers to trial enrollment included absence of a required biomarker (34%), withdrawal of consent (20%), deterioration or death (17%), other exclusion criteria (15%), and insufficient biopsy tissue (10%).
  
  
  CONCLUSIONS
  A growing number of NSCLC trials are requiring tumor tissue for treatment eligibility, which appears to be a significant barrier to trial enrollment. Potential solutions include use of available diagnostic samples (e.g., cytology samples), development of peripheral blood assays for molecular markers, faster central laboratory testing turnaround time, and more resources for rapid biopsy.
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Charles
authors.initials: C
authors.lastname: Lim
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Mike
authors.initials: M
authors.lastname: Sung
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Nazanin
authors.initials: N
authors.lastname: Nouriany
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Sawczak
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Tuhina
authors.initials: T
authors.lastname: Paul
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Nicole
authors.initials: N
authors.lastname: Perera-Low
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Foster
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Dianne
authors.initials: D
authors.lastname: Zawisza
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Ronald
authors.initials: R
authors.lastname: Feld
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Liu
authors.affiliation: Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Canada. Electronic address: Natasha.Leighl@uhn.ca.
authors.forename: Natasha B
authors.initials: NB
authors.lastname: Leighl
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000601:surgery*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010358:Patient Participation / Q000706:statistics & numerical data*; D018579:Patient Selection; D011379:Prognosis; D012720:Severity of Illness Index; D055815:Young Adult
keywords: Barrier; Clinical trial; Non–small cell lung cancer; Research biopsy