Efficacy and safety of nivolumab monotherapy in patients with unresectable clear cell sarcoma and alveolar soft part sarcoma (OSCAR Trial/NCCH1510)

• Published in: Cancer 2024-11, Vol.130 (22), p.3836-3844
• Main Authors: Nishikawa, Tadaaki, Kakunaga, Shigeki, Tamura, Kenji, Ando, Masashi, Ozaki, Toshifumi, Kawai, Akira, Ueda, Takafumi, Kawasaki, Mamiko, Tomatsuri, Sawako, Okamura, Nobuko, Kamikura, Masahisa, Hamada, Akinobu, Yoshida, Akihiko, Hirakawa, Akihiro, Shibata, Taro, Nakamura, Kenichi, Yonemori, Kan
• Format: Article
• Language: English
• Subjects: Adult; Aged; alveolar soft part sarcoma; Alveoli; Antineoplastic Agents, Immunological - adverse effects; Antineoplastic Agents, Immunological - therapeutic use; Bayesian analysis; clear cell sarcoma; Effectiveness; Female; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - adverse effects; Immune Checkpoint Inhibitors - therapeutic use; Male; Melanoma; Middle Aged; MITF‐associated tumor; nivolumab; Nivolumab - adverse effects; Nivolumab - therapeutic use; OSCAR Trial; Progression-Free Survival; Renal cell carcinoma; Safety; Sarcoma; Sarcoma, Alveolar Soft Part - drug therapy; Sarcoma, Alveolar Soft Part - pathology; Sarcoma, Clear Cell - drug therapy; Sarcoma, Clear Cell - pathology; Survival; Translocation; Young Adult
• ISSN: 0008-543X; 1097-0142; 1097-0142
• DOI: 10.1002/cncr.35483

ABSTRACT Background Clear cell sarcoma (CCS) and alveolar soft part sarcoma (ASPS) are rare, and standard systemic therapy is not established except for sunitinib in ASPS. It is known that CCS and ASPS have a common biological feature of melanoma and Xp11.2/TFE3 translocation renal cell carcinoma, and immune‐checkpoint inhibitors (ICIs) are effective in these tumors. The authors conducted a phase 2 trial to evaluate the efficacy and safety of nivolumab for CCS and ASPS. Methods The number of patients expected to be enrolled was 15–25 and was determined based on the Bayesian design. The primary end point was the confirmed objective response rate (ORR) according to the central review and the secondary end points included ORR, progression‐free survival (PFS), overall survival (OS), and safety. Results A total of 26 patients (CCS, 12; ASPS, 14) were enrolled. Efficacy and safety were analyzed on 25 and 26 patients, respectively. The minimum number of responses required for a positive conclusion regarding the efficacy was four. However, only one patient (4.0%) with ASPS had a partial response. Complete response, stable disease, progression disease, and not evaluable were 0%, 60%, 32%, and 4.0%, respectively. Adverse events of grade 3 or 4 occurred in 57.7% (15 of 26). The median PFS was 4.9 months (95% confidence interval [CI], 3.7–8.6 months) and the median OS was 15.8 months (95% CI, 8.2–not reached). Conclusions The primary end point of the ORR was not met for CCS and ASPS on the central review. Further studies are needed to evaluate ICIs in patients with ASPS. This study evaluated the efficacy and safety of nivolumab monotherapy for patients with clear cell sarcoma and alveolar soft part sarcoma in a single‐arm phase 2 trial. The results showed no clinical efficacy among patients with clear cell sarcoma, whereas further investigation was considered necessary among patients with alveolar soft part sarcoma.