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Durvalumab plus pazopanib combination in patients with advanced soft tissue sarcomas: a phase II trial

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  • Hee Jin Cho

    (CMRI, Kyungpook National University)

  • Kum-Hee Yun

    (Yonsei University College of Medicine)

  • Su-Jin Shin

    (Yonsei University College of Medicine)

  • Young Han Lee

    (Yonsei University College of Medicine)

  • Seung Hyun Kim

    (Yonsei University College of Medicine)

  • Wooyeol Baek

    (Yonsei University College of Medicine)

  • Yoon Dae Han

    (Yonsei University College of Medicine)

  • Sang Kyum Kim

    (Yonsei University College of Medicine)

  • Hyang Joo Ryu

    (Yonsei University College of Medicine)

  • Joohee Lee

    (Yonsei University College of Medicine)

  • Iksung Cho

    (Yonsei University College of Medicine)

  • Heounjeong Go

    (University of Ulsan College of Medicine)

  • Jiwon Ko

    (University of Ulsan College of Medicine
    Asan Medical Center)

  • Inkyung Jung

    (Yonsei University College of Medicine)

  • Min Kyung Jeon

    (Yonsei University College of Medicine)

  • Sun Young Rha

    (Yonsei University College of Medicine)

  • Hyo Song Kim

    (Yonsei University College of Medicine)

Abstract

We aimed to determine the activity of the anti-VEGF receptor tyrosine-kinase inhibitor, pazopanib, combined with the anti-PD-L1 inhibitor, durvalumab, in metastatic and/or recurrent soft tissue sarcoma (STS). In this single-arm phase 2 trial (NCT03798106), treatment consisted of pazopanib 800 mg orally once a day and durvalumab 1500 mg once every 3 weeks. Primary outcome was overall response rate (ORR) and secondary outcomes included progression-free survival (PFS), overall survival, disease control rate, immune-related response criteria, and safety. The ORR was 30.4% and the trial met the pre-specified endpoint. The median PFS was 7.7 months (95% confidence interval: 5.7–10.4). The common treatment-related adverse events of grades 3–4 included neutropenia (9 [19.1%]), elevated aspartate aminotransferase (7 [14.9%]), alanine aminotransferase (5 [10.6%]), and thrombocytopenia (4 [8.5%]). In a prespecified transcriptomic analysis, the B lineage signature was a significant key determinant of overall response (P = 0.014). In situ analysis also showed that tumours with high CD20+ B cell infiltration and vessel density had a longer PFS (P = 6.5 × 10−4) than those with low B cell infiltration and vessel density, as well as better response (50% vs 12%, P = 0.019). CD20+ B cell infiltration was identified as the only independent predictor of PFS via multivariate analysis. Durvalumab combined with pazopanib demonstrated promising efficacy in an unselected STS cohort, with a manageable toxicity profile.

Suggested Citation

  • Hee Jin Cho & Kum-Hee Yun & Su-Jin Shin & Young Han Lee & Seung Hyun Kim & Wooyeol Baek & Yoon Dae Han & Sang Kyum Kim & Hyang Joo Ryu & Joohee Lee & Iksung Cho & Heounjeong Go & Jiwon Ko & Inkyung Ju, 2024. "Durvalumab plus pazopanib combination in patients with advanced soft tissue sarcomas: a phase II trial," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44875-2
    DOI: 10.1038/s41467-024-44875-2
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    1. Florent Petitprez & Aurélien Reyniès & Emily Z. Keung & Tom Wei-Wu Chen & Cheng-Ming Sun & Julien Calderaro & Yung-Ming Jeng & Li-Ping Hsiao & Laetitia Lacroix & Antoine Bougoüin & Marco Moreira & Gui, 2020. "B cells are associated with survival and immunotherapy response in sarcoma," Nature, Nature, vol. 577(7791), pages 556-560, January.
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