One of the big problems we have is we don’t know where the majority of adolescents and young adults are being treated. We don’t know how many adolescents and young adults are being seen at NCI-designated cancer centers vs community hospitals.
Nita L. Seibel, MD
Although overall survival rates for patients with cancer continue to soar—with 14.5 million cancer survivors today1—most of that gain is among pediatric and older adult patients. For adolescents and young adults with cancer—defined by the National Cancer Institute (NCI) as those in the 15- to 39-year-old range—improvement in survival has been significantly less, remaining stagnant since 1975. According to a review2 of several population-based analyses,3-6 by Nita L. Seibel, MD, and her colleague, David R. Freyer, DO, MS [Director of the Survivorship and Supportive Care Program at Children’s Hospital Los Angeles], “there has been a sustained failure to improve 5-year survival for adolescents and young adults at rates comparable to either younger or older patients.”
There are myriad reasons why survival rates for adolescents and young adults have failed to see substantial improvement, including age-related differences in tumor biology, increased treatment-related toxicity and mortality, lower adherence to prescribed therapy, delayed access to care, and lower participation in clinical trials. “While deficits in areas such as health insurance and psychosocial support constitute important gaps for adolescents and young adults, enrollment into NCI-funded clinical trials remains pivotal for improving survival and related outcomes,” said Dr. Seibel.
The ASCO Post talked with Dr. Seibel, Head of Pediatric Solid Tumor Therapeutics at the National Cancer Institute, about the results of her study, how oncologists can encourage adolescent and young adult patients to enroll in clinical trials, and the significance of tumor biology on adolescent and young adult survivorship.
Where Patients Are Seen
Over the past 4 decades, survival rates for adolescents and young adults with cancer have remained flat, even as rates for younger and older patients have made dramatic gains. Please talk about the findings from your study and how poor representation by adolescents and young adults in clinical trials may be contributing to their lower survival rates.
We reviewed a variety of data documenting low enrollment in clinical trials by adolescents and young adults and its impact on survival. One of the reasons we feel that adolescents and young adults are not seeing the progress or improvement in their survival compared with either younger or older patients is because they are not getting into clinical trials, and part of that may be related to where they are seen.
Because adolescents and young adults fall into such a wide age range—between 15 and 39 years—these patients, especially those in the young adult age range, are more likely to be seen by a community medical oncologist in a community hospital, rather than a pediatric oncologist at an academic cancer center or a pediatric oncology center. A community oncologist may not be as attuned to the vast clinical trials system as a pediatric oncologist at an academic center, where treatment usually hinges on participation in clinical trials. We know that over 90% of pediatric patients go into clinical trials, whereas only about 10% of older adolescents enroll in clinical trials.7 When a pediatric oncologist has a new adolescent or young adult patient, she or he will look to see whether there is an appropriate trial available for that patient. That doesn’t always happen in the community oncology setting.
There are multiple factors that go into play, of course, but we do feel that where adolescents and young adults are seen initially is very important. We need to make sure these patients are aware of clinical trials and get to the institutions with the latest treatment or clinical trials available.
Finding Appropriate Trials
What are some of the other barriers to greater participation by adolescents and young adults in clinical trials?
There are several. In some instances, the patient may have to be sent to another center for enrollment into a trial, and some physicians are not willing to do that and lose a patient. Also, putting a patient into a trial takes a lot of time. The physician has to understand the purpose of the study to explain it to the patient and obtain the patient’s consent, and some medical oncologists are not able to devote that much time to the process.
The NCI has helped simplify finding appropriate trials for patients through the NCI National Clinical Trials Network (NCTN) [formerly the NCI Clinical Trials Cooperative Group Program] with the use of the NCI Central Institutional Review Board. So when a study protocol is approved by the NCI, it is reviewed by the Central Institutional Review Board; once approved, it is then posted on the Cancer Trials Support Unit, which facilitates access to NCTN clinical trials. The protocol can then be downloaded at the institution where the patient is being seen, and the patient can then be enrolled; so the process is faster and doesn’t take as much manpower as before the NCTN, Central Institutional Review Board, and Cancer Trials Support Unit were all in place.
Is there a way to design clinical trials for adolescents and young adults to make them more attractive for them to enroll?
We do not have enough data to know the answer to that question. One of the big problems we have is we don’t know where the majority of adolescents and young adults are being treated. We don’t know how many adolescents and young adults are being seen at NCI-designated cancer centers vs community hospitals. We can’t even say now how many patients are being offered a clinical trial and if they are offered a trial how many are turning it down.
These are areas we need to study to understand where the communication is breaking down. Are patients not participating in trials because they don’t want to come back to the center for follow-up visits or because they don’t want to have to travel longer distances to get to the clinical trial site? We just don’t have the data to say exactly why an adolescent or young adult would not go on a clinical trial.
What are you learning about the differences in tumor biology and survivorship between adolescents and young adults and younger and older patients?
This is a huge area of interest, but it has not been studied extensively so far. If patients do not participate in clinical studies, it is difficult to collect and bank tumor tissue to test differences in specific tumor types in adolescents and young adults and older adults. Over the past 10 years, researchers started to investigate why an adolescent or young adult who developed acute lymphoblastic leukemia (ALL) has a poorer outcome than a younger patient with ALL and why some young adults with breast cancer do not do as well as older adults with breast cancer, but we do not have definitive answers yet.
A group of researchers led by Charles G. Mullighan, MD, of St. Jude Children’s Research Hospital, performed genomic analysis8 of patients with Philadelphia chromosome–like ALL and identified kinase-activating alterations in the vast majority of patients. And this subtype of ALL is more difficult to treat and tends to be more resistant to treatment, causing a worse outcome in these patients. However, Dr. Mullighan’s study suggests that tyrosine kinase inhibitor therapy may be effective in these adolescents and young adults. So this is exciting news because we are finally able to identify some biologic differences among younger, adolescents and young adults, and older adults.
Encouraging Trial Participation
What can ASCO members do to encourage young patients to enroll in clinical trials?
The main thing is bringing up the subject of clinical trials with their adolescents and young adults and then educating them about the value of participating in a clinical study. Having these conversations with patients does take time, but the knowledge gained from these studies will help not only current patients but future patients as well. ■
Disclosure: Dr. Seibel reported no potential conflicts of interest.
1. American Cancer Society: Cancer Treatment & Survivorship Facts & Figures 2014–2015. Available at cancer.org/acs/groups/content/@research/documents/document/acspc-042801.pdf. Accessed February 16, 2016.
2. Freyer DR, Seibel NL: . Curr Pediatr Rep. February 18, 2015 (online).
3. Albritton K, Bleyer WA: Eur J Cancer 39:2584-2599, 2003.
4. Bleyer A, Montello M, Budd T, et al: Cancer 103:1891-1897, 2005.
5. Adolescent and Young Adult Oncology Progress Review Group: Closing the gap. Bethesda, National Institutes of Health, 2006. NIH Publication 06-6067.
6. Bleyer A, O’Leary M, Barr R, et al: Cancer epidemiology in older adolescents and young adults 15-29 years of age. Bethesda, National Institutes of Health, 2006. NIH Publication 06-5767.
7. Beaupin L: Are adolescents overlooked in clinical trials? Roswell Park Cancer Institute, May 2013. Available at roswellpark.org/cancertalk/201305/are-adolescents-overlooked-clinical-trials. Accessed February 16, 2016.
8. Roberts KG, Li Y, Payne-Turner D, et al: N Engl J Med 371:1005-1015, 2014.