Long-term adverse events were rare and manageable among patients with alveolar soft part sarcoma (ASPS), which primarily affects adolescents and young adults, who received immunotherapy beyond the standard 2 years, according to results from a phase II clinical trial presented at the American Association for Cancer Research (AACR) Annual Meeting 2026 (Abstract CT004). Results from this study were simultaneously published in the Journal of Clinical Oncology.
For most patients receiving immune checkpoint inhibitors for their cancer, the recommendation is to stop treatment after 2 years based on the duration of treatment established in early trials, as well as additional evidence indicating 2 years may offer sufficient benefit in lung cancer and melanoma. However, there has been a lack of clinical data on the long-term use of immune checkpoint inhibitors to treat ASPS, an ultrarare cancer with incidence rates highest among 15- to 35-year-olds, explained Alice P. Chen, MD, Head of the Developmental Therapeutics Clinic in the Division of Cancer Treatment and Diagnosis at the National Cancer Institute (NCI), part of the National Institutes of Health (NIH).
In December 2022, the immune checkpoint inhibitor atezolizumab was approved by the U.S. Food and Drug Administration for patients aged 2 years and older with ASPS based on early results from an ongoing phase II trial being conducted by Dr. Chen and her colleagues. At the time of approval, 42% of the 49 patients enrolled in the study had a duration of response lasting 12 months or more.
“Because many patients experienced durable responses and remained on immunotherapy for several years, we wanted to understand the potential long-term effects of this treatment, particularly for adolescents and young adults with ASPS who may receive immunotherapy for extended periods,” Dr. Chen said. “Studying the risk of late adverse events during and following prolonged treatment helps ensure that these therapies remain safe for this young patient population.”
Key Findings
As of June 2025, investigators had enrolled 54 patients in the trial; the duration of their responses to atezolizumab ranged between 10 and 69 months. Patients older than 2 years received 1,200 mg of atezolizumab every 3 weeks or a pediatric dose of 15 mg/kg up to 1,200 mg. If disease progressed, adult patients were given the option to receive the vascular endothelial growth factor inhibitor bevacizumab in combination with atezolizumab. Patients were assessed for adverse events every 3 weeks using version 5 of the Common Terminology Criteria for Adverse Events. Seventeen patients between the ages of 11 and 56, with a median age of 29, received either atezolizumab (n = 12) or atezolizumab followed by atezolizumab plus bevacizumab (n = 5) for more than two years.
“Because ASPS is an ultrarare cancer, studies in this population are necessarily small,” Dr. Chen explained. “For the long-term analysis, these 17 patients provided valuable insight into the safety of long-term atezolizumab therapy.”
Of the 17 patients, three experienced treatment-related adverse events that were grade 2 or 3. One patient who was receiving atezolizumab plus bevacizumab experienced grade 3 aspartate aminotransferase (AST); another patient who was receiving atezolizumab plus bevacizumab experienced grade 2 hypertension and grade 2 proteinuria; and one patient who was receiving atezolizumab monotherapy experienced grade 2 pruritus.
“Among patients who received immunotherapy for longer than 2 years, we did not observe evidence of increased toxicity—and this finding held even among patients treated for more than 5 years,” Dr. Chen said. “This is especially important for adolescents and young adults with ASPS who may live for many years with metastatic disease.”
Dr. Chen added that none of the atezolizumab-related treatment-related adverse events resulted in individuals discontinuing with the study and all the symptoms were eventually resolved. The pruritus was treated with topical and oral medication, the increased AST resolved after a dose reduction of bevacizumab, and the hypertension resolved after treatment with hypertension medication.
“Importantly, we did not observe the late [treatment-related adverse events] sometimes seen with long-term use of immunotherapy for other cancers, such as lung cancer,” Dr. Chen added. “This may be related to the younger age of the patients or the unique biology of ASPS. With the approval of atezolizumab for this indication in multiple countries, real-world data will also play an important role in understanding the long-term effects of immunotherapy in this patient population.”
Limitations of this study include the size of the patient population. The trial protocol allowed patients to take an atezolizumab drug holiday after 2 years of progression-free treatment, which further reduced the number of patients who were treated beyond 2 years.
DISCLOSURE: This study was supported by federal funding from the NCI and NIH and was partly supported by Genentech Inc., which provided the drug and funding. The NCI has a Cooperative Research and Development Agreement (CRADA) with Genentech and AstraZeneca. For full disclosures of the study authors, visit ascopubs.org.
