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INVITED ARTICLES
GASTROINTESTINAL CANCER
Perspectives on Clinical Trials for Gastrointestinal Malignancies
Cathy Eng, MD, FACP, Nancy Roach, Michele Longabaugh, RN, and George Fisher, MD, PhD
We all accept the premise that clinical trials are essential
to improving the care and outcomes of those afflicted
with cancer. Indeed, without successful enrollment into clinical
trials, there would be no new diagnostics or treatments
for cancer. Yet, it is often quoted that fewer than 5% of adult
patients with cancer participate in clinical trials. The dismal
accrual rates have been the subject of many learned reviews.
In this article, two academic oncologists, a patient advocate
and a cancer survivor/author contribute our perspectives on
the problem and have chosen to focus on gastrointestinal
cancers in the United States as our example.
THE PROBLEM: THE PHYSCIAN PERSPECTIVE
First, we must ask if the approximately 5% participation rate
in clinical trials is accurate, and of whom this 5% comprises.
Murthy et al 1 calculated an enrollment fraction of 1.7% in
National Cancer Institute (NCI)–sponsored clinical trials divided
by the total estimated cancer cases in the United States.
Whereas 3.0% of patients age 30 to 64 enrolled in a clinical
trial, but only 1.3% of those age 65 to 74 participated. Given
that the median age of diagnosis of a gastrointestinal (GI)
malignancy is 71 2 , it is clear that the majority of patients with
GI cancer (i.e., those 65 and older) are underrepresented. In
another snapshot of recent accrual, Al-Refaie et al 3 noted that
of the 244,528 patients (with melanoma, breast, lung, esophagus,
gastric, liver, pancreas, colon, rectum, or anal cancers)
in the California Cancer Registry between 2001 and 2008, a
meager 0.64% enrolled in a clinical trial. The enrollment rate
was even further reduced among blacks compared with
whites (0.48% vs. 0.67%, p 0.05). Of those who did enroll,
97% had some form of health insurance and 3% listed insurance
as either none or unknown. During this same period of
time, it was estimated that 29.5% of California adults were
uninsured. 4 Clearly, lack of insurance has been a major barrier
to accrual. In sharp contrast, in 2007, the United Kingdom
reported 32,000 patients (14% of the annual U.K. cancer
incidence) were enrolled in clinical trials. 5 In 2014, the number
of patients enrolled has increased dramatically to more
than 60,000. 6
Even among those who are eligible and insured, access to a
trial is not a certainty. Of the 4,617 patients enrolled in a clinical
trial 7 at John Hopkins Medicine (2003 to 2008), 628 patients
(13.6%) were denied trial enrollment because of refusal
of insurance coverage. To date, these challenges remain, and
they appear to be mounting given the arduous amount of additional
work that is sometimes required of health care providers.
With the approval of the Affordable Care Act (ACA),
it is expected that there will be increased patient enrollment
since insurance providers are required by law to provide for
routine patient costs associated with clinical trials. 7
Recognizing the ineffıciencies inherent to NCI-sponsored
cooperative group research, the Institute of Medicine prompted
a reduction/merger of cooperative groups with the intention
of reducing redundancy and expediting the design and conduct
of clinical trials. 8 As per the NCI’s Operational Effıciency
Working Group (OEWG) report, this has made some
initial effect in regards to reinforcing investigators to follow a
tight timeline. 9 Yet, the reimbursement rate per patient enrolled
(approximately $2,000 per patient) has not changed
for over a decade. This results in a fınancial loss to the institution
and is an additional disincentive to open and accrue to
NCI cooperative group trials. Furthermore, the effect of
U.S. government budge sequestration adversely affected
all aspects of research development from bench to bedside.
10 With increasing costs of research, largely due to the
limitations of drug accessibility, even pharmaceuticalsponsored
studies are being referred overseas because of
the reduced costs and rapid enrollment compared with the
United States. For example, when surveying 20 of the largest
U.S. pharmaceutical companies, it is reported that up
to one-third of phase III clinical trials are being conducted
overseas. 11-13
Personalized (or precision) medicine adds complexity to
clinical trial enrollment. Patients and oncologists are more
frequently ordering molecular profıling of tumor samples,
with the hope of fınding an actionable target. Patients are
From The University of Texas MD Anderson Cancer Center, Houston, TX; Stanford University School of Medicine, Stanford, CA.
Disclosures of potential conflicts of interest are found at the end of this article.
Corresponding author: Cathy Eng, MD, FACP, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030; email: ceng@mdanderson.org.
© 2015 by American Society of Clinical Oncology.
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