Joint Adult and Pediatric Working Group as a Successful Platform to Strengthen Adolescent and Young Adult (AYA) Clinical Trial Collaboration: A Report from the NCTN/SARC AYA Clinical Trials Sarcoma Working Group

To the Editor:

Each year an estimated 80,000 adolescents and young adults (AYAs) aged 15–39 years are diagnosed with cancer in the United States. ¹ Although bone and soft tissue sarcomas are relatively rare cancers, there is an incidence peak such that half of sarcoma diagnoses occur in the AYA age range. ² Clinical trial participation is vital to advance knowledge in host and tumor biology, understand epidemiology, provide early access to novel therapeutics, and define optimal treatment approaches. However, studies show that only 3%–14% of AYAs enroll in clinical trials. ³ Sarcoma treatment is fundamentally multidisciplinary and requires frequent communication between surgical, radiation, and adult/pediatric oncology to guide medical decision-making. AYA sarcoma care represents an opportunity to define best practices to address AYA clinical trial enrollment challenges.

Considerable work has been done to strengthen the research networks within the National Cancer Institute (NCI), National Clinical Trials Network (NCTN), NCI Community Oncology Research Program (NCORP), and Sarcoma Alliance for Research Through Collaboration (SARC) organization. ³ Despite these efforts, AYA access overall to clinical trials continues to be limited by the lack of trial availability, location of trial site, regulatory concerns, and limited communication between adult and pediatric oncologists. ¹ Historically within sarcoma, reported trial enrollment barriers include disagreement over proposed therapeutic approach, toxicity concerns, lack of awareness, and/or competing trials. ⁴

In September 2019, the NCTN/SARC AYA Clinical Trials Sarcoma Working Group was formed. The mission of the working group is to increase clinical trial enrollment of AYA patients with sarcoma through physician collaboration, multidisciplinary approach, resourcefulness, and inclusivity. Current members represent all five NCTN cooperative groups as well as SARC and include radiation oncology, surgical oncology, adult, and pediatric oncologists. The working group format is monthly virtual meetings with alternating presentations from representative cooperative groups. All phases of clinical trials are discussed with early trial concepts prioritized, but protocols further in development are also encouraged. To date, four cooperative groups have presented a total of 13 sarcoma trial concepts/protocols (Table 1).

The members of this grassroots working group have provided vital input on trial concept development, preferred protocol design, avoidance of competitive trials, and fostered discussion regarding toxicity concerns of therapy backbones. This effort has led to increased cross-network physician endorsement of clinical trials and designation of AYA champions on NCTN trials to enhance cross-group enrollment.

AYA patients continue to be underrepresented in pediatric and adult oncology clinical trials.

The barriers to AYA clinical trial enrollment remain multifactorial; however, research has identified several facilitators to enhance AYA enrollment.^1,2 Central to improving AYA care will be the development and endorsement of collaborative cross-network therapeutic and supportive care trials between pediatric and medical oncology research groups. The NCTN/SARC AYA Clinical Trials Sarcoma Working Group provides proof of concept of this principle and is improving clinical trial collaboration for AYA patients diagnosed with sarcoma.

Future directions of the working group include widespread incorporation of patient-reported outcomes into AYA clinical trials, the co-development of supportive care trials between pediatric and adult cooperative groups, enhancing the patient advocate perspective, and encouragement of young investigator-led concepts. ⁵