Prolonged Use of Immunotherapy in Alveolar Soft Part Sarcoma: Safety and Tolerability Beyond Two Years

Results from a phase 2 clinical trial presented at the annual meeting of the American Association for Cancer Research (AACR), held April 17 – 22, 2026 and published simultaneously in the Journal of Clinical Oncology has provided new insight into the safety of long-term immune checkpoint inhibitor therapy in patients with alveolar soft part sarcoma (ASPS)—an ultra rare cancer affecting mainly adolescents and young adults (AYAs). [1][2][3][4]

Alveolar soft part sarcoma (ASPS) is an ultra-rare soft tissue sarcoma with peak incidence among individuals aged 15 to 35. [1] The disease is known for its indolent course and tendency to affect younger patients, who may live with metastatic disease for many years. Immune checkpoint inhibitors (ICIs), such as atezolizumab (Tecentriq® Genentech), have transformed the treatment landscape for several cancers, but the optimal duration of therapy—particularly in rare sarcoma subtypes—remains unclear.

For most cancer patients receiving immune checkpoint inhibitors (ICIs), the recommendation is to stop treatment after two years. This recommendation is based on the treatment duration established in early clinical trials, as well as additional evidence indicating that two years may offer sufficient benefit in lung cancer and melanoma.

“However, data on extended use in ASPS has been lacking,” noted 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).

Clinical Trial Design and Patient Population
The ongoing phase 2 trial, led by Chen, enrolled 54 patients with unresectable or metastatic ASPS, and the duration of atezolizumab response ranged from 10 to 69 months. Patients older than 2 years received atezolizumab at 1,200 mg every three weeks (or a pediatric dose of 15 mg/kg up to 1,200 mg). If the disease progressed, adults could receive additional therapy with bevacizumab (Avastin®; Genentech/Roche), a VEGF inhibitor, in combination with atezolizumab.

Patients were assessed for adverse events every three weeks using version 5 of the Common Terminology Criteria for Adverse Events (CTCAE). Seventeen patients (ages 11–56, median 29) continued immunotherapy for more than two years (over 34 cycles), including 12 who received atezolizumab monotherapy and five who received combination therapy after initial monotherapy.

“Because ASPS is an ultra-rare cancer, studies in this population are necessarily small,” Chen said. “For the long-term analysis, these 17 patients provided valuable insight into the safety of long-term atezolizumab therapy.”

Adverse Events Beyond Two Years
Among these 17 long-term treated patients, three (18%) experienced new treatment-related adverse events (TRAEs) of grade 2 or 3 severity after two years:

• One patient on combination therapy developed grade 3 aspartate aminotransferase (AST) elevation, indicating possible liver toxicity.
• Another patient on combination therapy experienced grade 2 hypertension and grade 2 proteinuria, suggesting kidney involvement.
• One patient on monotherapy developed grade 2 pruritus (itching), which resolved with medication and a temporary treatment break.

Importantly, the researchers did not report any grade 4 or 5 toxicities, while all adverse events resolved, and none of the patients discontinued treatment due to toxicity. The frequency and severity of late-onset adverse events did not appear to increase with longer treatment duration, even in patients treated for more than five years.

Relevance and Implications
These findings are especially important for the AYA population, who may require prolonged therapy and could be at risk for cumulative or late toxicities. Unlike some other cancers, where extended ICI therapy can result in delayed severe adverse events, such as pneumonitis or endocrinopathies, the ASPS cohort did not demonstrate these late complications. The reasons may relate to the younger age of patients or distinct tumor biology.

At the time of the study, atezolizumab was approved in the U.S. for ASPS in patients aged two and older, based on earlier phase 2 trial results demonstrating a 37% objective response rate (ORR) and durable responses. The approval was based on early results from an ongoing phase 2 trial being conducted by Chen and her colleagues. At the time of approval, a significant proportion of patients (42% of the 49 participating patients) had a response duration of 12 months or longer, with ongoing follow-up indicating some responses beyond five years.

“Among patients who received immunotherapy for longer than two years, we did not observe evidence of increased toxicity, and this finding held even among patients treated for more than five years,” Chen said. “This is especially important for adolescents and young adults with ASPS, who may live for many years with metastatic disease,” she explained.

“Importantly, we did not observe the late TRAEs sometimes seen with long-term use of immunotherapy for other cancers, such as lung cancer,” Chen noted.

“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,” she added.

Study Limitations As an ultra-rare cancer, the ASPS study was necessarily small. Additionally, the protocol allowed for drug holidays after two years of progression-free therapy, further limiting the number of patients exposed to prolonged treatment. Larger, real-world datasets will be important to better understand the risk profile of long-term immunotherapy in this and related populations.

Long-term use
Long-term atezolizumab therapy, alone or with bevacizumab, was well tolerated in adolescents and adults with ASPS, with late adverse events being rare, manageable, and reversible. These results provide reassurance to clinicians and patients regarding the safety of extended immunotherapy in this young patient population and support continued investigation of optimal treatment durations in rare sarcomas.

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Note: * This study was supported by the NCI, NIH, and Genentech, with no conflicts of interest declared by the lead investigator. Clinical trial

Clinical trials
Testing Atezolizumab Alone or Atezolizumab Plus Bevacizumab in People With Advanced Alveolar Soft Part Sarcoma – ClinicalTrials.gov ID NCT03141684

Highlights of prescribing information
Atezolizumab (Tecentriq® Genentech)[Prescribing Information]
Bevacizumab (Avastin®; Genentech/Roche)[Prescribing Information]

Reference
[1] Jaber OI, Kirby PA. Alveolar Soft Part Sarcoma. Arch Pathol Lab Med. 2015 Nov;139(11):1459-62. doi: 10.5858/arpa.2014-0385-RS. PMID: 26516944.
[2] Chen AP, Moore N, Foster J, Rosenberger C, O’Sullivan Coyne G, Glod J, Hu J, Conley A, Read W, Despande H, Schwartz G, Chen J, Okuno S, Riedel R, Sharon E,  Doroshow J. In: Proceedings of the 117th Annual Meeting of the American Association for Cancer Research; 2026 April 17-22; San Diego, CA.: AACR; 2026. Abstract nr CT004.
[3] Chen AP, Sharon E, O’Sullivan-Coyne G, et al. Atezolizumab for Advanced Alveolar Soft Part Sarcoma. New Engl J Med 2023;389:911-921.
[4] Chen AP, Rosenberger CL, Moore N, Foster JC, Naqash AR, Sharon E, O’Sullivan Coyne G, Schwartz GK, Riedel RF, Glod J, Hu JS, Conley AP, Read WL, Burgess MA, Davis EJ, Merriam P, Deshpande HA, Ladle BH, Okuno SH, Beck JC, Chen JL, Ferry-Galow KV, Fino KK, Miller BL, Wilsker DF, Begum A, Parchment RE, Doroshow JH. Atezolizumab for Alveolar Soft Part Sarcoma: A Clinical Trial Update. J Clin Oncol DOI: 10.1200/JCO-25-02811

Featured image: AACR-2016-New-Orleans, LA. Photo courtesy: © 2016 – 2026 AACR. Used with permission.

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