Children with acute lymphoblastic leukemia gain little by participating in clinical trials

ABSTRACT: Parents and their children need to understand that advancing science does not always go hand-in-hand with a direct benefit to the patients.

Although it is widely held that clinical trial participation is the best treatment option for patients with cancer, a new study casts doubt on that assumption. Physicians at one pediatric academic institution concluded that patients with newly diagnosed acute lymphoblastic leukemia who took part in contemporary clinical trials did not have significantly improved outcomes compared with their counterparts who did not participate in clinical trials.

"In contrast to similar retrospective studies from earlier treatment eras, our study failed to show a benefit for clinical trial participation, ie, 'a trial effect,'" said coauthor Blythe Thomson, MD, a pediatric oncologist at Seattle Children's Hospital.

"In contrast to similar retrospective studies from earlier treatment eras, our study failed to show a benefit for clinical trial participation."- Blythe Thomson, MD

For this retrospective research, Dr. Thomson and colleagues used data from 322 patients with newly diagnosed ALL who were treated at the Seattle institution between 1997 and 2005. All patients were younger than 22 years. Of the 322 patients, 157 participated in a clinical trial and 165 did not (Arch Pediatr Adolesc Med 164:214-217, 2010).

No significant difference in five-year event-free survival (EFS) was observed between the two groups. Overall, the five-year EFS was 79% for all subjects; five-year EFS was 80% for those who did not participate in trials compared with 77% for trial participants. Analysis of demographic factors showed that sex, race, home state, and distance from primary residence did not account for participation in a clinical trial. However, standard-risk patients were more likely to participate in a clinical trial than high-risk patients (54% vs 43%, respectively).

Dr. Thomson acknowledged that a potential explanation for the similar outcomes is that trial nonparticipants were cared for at her institution, a large academic center, where all children are treated according to the best evidence-based protocols. "All patients received therapy according to strictly defined institutional standard therapies based on the most recent clinical trial results," she said.

Currently, five-year survival rates for pediatric ALL range from 80% to 90%, which is largely due to advances in therapy made possible by clinical trials, particularly in pediatric cancer care centers that have the infrastructure to support such trials.

The authors concluded that because clinical trial participation per se did not improve outcomes for pediatric patients with ALL, discussion with patients and families about clinical trial participation should focus on the potential to improve future therapy, not direct benefit to the trial participant. n

VANTAGE POINTFamilies need to carefully consider pros, cons of joining a trial

The results of this study remind physicians that "the reason to consider a clinical trial is because this is how we move the field forward and keep improving treatments for children with cancer, not because we can say for sure that joining a trial is the best way to treat the patient," Dr. Joffe wrote in an accompanying editorial.

"This study is fairly convincing that if you are a child with ALL treated at a cancer center like the Seattle Children's Hospital, there is no reason to believe that there will be a difference in outcomes depending on whether you participate in a clinical trial," said Dr. Joffe, who is in the department of pediatric oncology at Boston's Dana-Farber Cancer Institute (Arch Pediatr Adolesc Med 164:293-294, 2010).

Dr. Joffe emphasized that he strongly supports clinical trial participation for children with cancer. He encouraged any family facing a diagnosis of cancer to ask which clinical trials are being offered, and to carefully consider the risks and benefits of each of those choices.

"With some cancers, the decision is not as urgent as with others," he noted, and so families should take time to make the decision. He also advised bringing a third-party advocate along for discussion with the doctor as a "sounding board." Finally, he suggested that families revisit the decision after they have been able to absorb the fact of the cancer diagnosis and have another consultation with the doctor or a research nurse to make sure they fully understand the clinical trial they've joined.

"An important implication of [this] study is that families of children with ALL who are not candidates for clinical trials do not have to be concerned if they can't enter a clinical trial. They can feel just as good about getting evidence-based therapy at a good children's cancer center," Dr. Joffe said.