DALLAS – Sept. 26, 2014 – Lung cancer clinical trials exclude a substantial proportion of patients due to a history of prior cancer, as shown in an analysis by cancer researchers at UT Southwestern Medical Center.
Among more than 50 lung cancer clinical trials examined, more than 80 percent excluded patients with prior cancer from participating, according to the study published in the Journal of the National Cancer Institute. The exclusion criterion was even applied in more than two-thirds of trials in which survival was not the primary endpoint.
"Our research demonstrates that a substantial proportion of potential subjects are reflexively excluded from lung cancer clinical trials due to prior cancer," said lead author Dr. David Gerber, Associate Professor of Internal Medicine in the division of Hematology and Oncology. In many cases, prior cancer seems to be the only reason for study ineligibility, even though the prior cancer seems unlikely to interfere with the treatment or outcomes of the current lung cancer, Dr. Gerber explained.
"The resulting impact on study accrual is sobering," said Dr. Gerber, a co-leader of the Experimental Therapeutics Program and co-director of the Lung Disease Oriented Team at the Harold C. Simmons Cancer Center at UT Southwestern. "The proportion of potential patients excluded due to prior cancer per trial ranged up to 18 percent, with the estimated absolute number of excluded patients per trial ranging up to 207." Dr. Gerber projected that these effects will only increase with time; there are currently more than 13 million cancer survivors in the U.S., which is a four-fold increase over the past 30 years.
Researchers examined lung cancer trials conducted by the Eastern Cooperative Oncology Group (ECOG), a National Cancer Institute (NCI)-funded organization that designs and conducts cancer clinical trials. Even within this organization, prior cancer eligibility criteria varied widely. Forty-three percent of trials excluded patients with prior cancer diagnosed within 5 years of study enrollment, 16 percent of trials excluded those with active cancer, 14 percent excluded those with any history of cancer, and 7 percent of trials excluded patients who had cancer within the past two to three years.
Nationwide, fewer than 2 percent of adults participate in clinical trials, with stringent eligibility criteria a key barrier to patient enrollment. Other reasons for low participation include limited access to clinical trials and lack of patient interest.
Additional studies are needed to determine whether or not prior cancer exclusion criteria are justified, Dr. Gerber said.
"If future studies demonstrate that prior cancer does not limit lung cancer treatment options or adversely impact clinical outcomes, modifying or eliminating this longstanding and arbitrary exclusion policy in lung cancer clinical trials may result in more generalizable results, faster accrual, higher completion rates, and the delivery of better treatments to more patients sooner," Dr. Gerber said. "Because clinical trial design is relatively centralized, we believe that implementation of such changes could occur rapidly."
Such changes would be particularly welcome for lung cancer, which causes more deaths than any other cancer in both men and women. According to the American Cancer Society, an estimated 224,210 new cases of lung cancer are expected in 2014, accounting for about 13 percent of all cancer diagnoses.
"Randomized clinical trials in cancer tend to focus on a narrow, homogenous group of individuals. This study shows the impact on the overall population of such an approach. As treatment both for cancer and other life-threatening diseases improves, there are more and more long-term cancer survivors in the U.S. These people can sometimes get a second cancer later in life. It is really important from a clinical and policy perspective to be able to include such individuals in cancer trials so we have more representative information about how well cancer treatments work in this growing subgroup of patients/cancer survivors," said co-author Dr. Ethan Halm, Chief of the William and Gay Solomon Division of General Internal Medicine, and Chief of the Division of Outcomes and Health Services Research in the Department of Clinical Sciences at UT Southwestern.
Support for the study included a National Cancer Institute Clinical Investigator Team Leadership Award, and grants by the American Cancer Society, Harold C. Simmons Cancer Center, the Cancer Prevention Research Institute of Texas (CPRIT), and the UT Southwestern Center for Patient-Centered Outcomes Research.
UT Southwestern earlier this year established a Center for Patient-Centered Outcomes Research that supports and conducts high-quality research comparing the outcomes and effectiveness of different strategies to prevent, diagnose, treat, and monitor health conditions to improve patient care. The center, part of a national network of seven institutions, is funded through a $5 million, five-year grant from the federal Agency for Healthcare Research and Quality (AHRQ), and led by co-author Dr. Halm, who holds the Walter Family Distinguished Chair in Internal Medicine in Honor of Albert D. Roberts, M.D.
UT Southwestern's Harold C. Simmons Cancer Center is the only National Cancer Institute-designated cancer center in North Texas and one of just 66 NCI-designated cancer centers in the nation. The Harold C. Simmons Cancer Center includes 13 major cancer care programs with a focus on treating the whole patient with innovative treatments, while fostering groundbreaking basic research that has the potential to improve patient care and prevention of cancer worldwide. In addition, the Center's education and training programs support and develop the next generation of cancer researchers and clinicians.
Other UT Southwestern researchers involved include Dr. Sandi Pruitt, Assistant Professor of Clinical Science; Dr. Andrew Laccetti, Department of Internal Medicine; and Lei Xuan, biostatistical consultant in Clinical Sciences.
About UT Southwestern Medical Center
UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. Numbering more than 2,700, the faculty is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to nearly 91,000 hospitalized patients and oversee more than 2 million outpatient visits a year.
JNCI Journal of the National Cancer Institute