Trabectedin and immune checkpoint inhibitors: a blissful combination or another failure in soft tissue sarcomas?

Papers of special note have been highlighted as: • of interest

References

• 1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J. Clin. 70(1), 7–30 (2020).
  MedlineGoogle Scholar
• 2. Assi T, Kattan J, El Rassy E et al. A comprehensive review of the current evidence for trabectedin in advanced myxoid liposarcoma. Cancer Treat. Rev. 72, 37–44 (2019).
  Medline CASGoogle Scholar
• 3. Belgiovine C, Frapolli R, Liguori M et al. Inhibition of tumor-associated macrophages by trabectedin improves the antitumor adaptive immunity in response to anti-PD-1 therapy. Eur. J. Immunol. 51(11), 2677–2686 (2021).
  Medline CASGoogle Scholar
• 4. Borghaei H, Paz-Ares L, Horn L et al. Nivolumab versus docetaxel in advanced nonsquamous non–small-cell lung cancer. N. Engl. J. Med. 373(17), 1627–1639 (2015).
  Medline CASGoogle Scholar
• 5. D'Angelo SP, Mahoney MR, Van Tine BA et al. Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): two open-label, non-comparative, randomised, phase 2 trials. Lancet Oncol. 19(3), 416–426 (2018). • One of the first clinical trials demonstrating limited activity of immune checkpoint inhibitors in soft tissue sarcomas.
  MedlineGoogle Scholar
• 6. Martin Broto J, Hindi N, Grignani G et al. Nivolumab and sunitinib combination in advanced soft tissue sarcomas: a multicenter, single-arm, phase Ib/II trial.. J Immunother Cancer 8(2), e001561 (2020). • Promising results for the combination strategy of immune checkpoint inhibitors and targeted therapy.
  MedlineGoogle Scholar
• 7. Digklia A, Coukos G, Homicsko K. Trabectedin and durvalumab combination is feasible and active in relapsing ovarian cancer. Clin. Cancer Res. 28(9), 1745–1747 (2022).
  Medline CASGoogle Scholar
• 8. Germano G, Frapolli R, Simone M et al. Antitumor and anti-inflammatory effects of trabectedin on human myxoid liposarcoma cells. Cancer Res. 70(6), 2235–2244 (2010).
  Medline CASGoogle Scholar
• 9. Chamseddine AN, Assi T, Mir O, Chouaib S. Modulating tumor-associated macrophages to enhance the efficacy of immune checkpoint inhibitors: A TAM-pting approach. Pharmacol. Ther. 231, 107986 (2021). • An important overview of the strategy for modulating tumor-associated macrophages to enhance the activity of immune checkpoint inhibitors.
  MedlineGoogle Scholar
• 10. Germano G, Frapolli R, Belgiovine C et al. Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell 23(2), 249–262 (2013).
  Medline CASGoogle Scholar
• 11. Griffith T, James B. Tumor necrosis factor-related apoptosis-inducing ligand-induced apoptotic pathways in cancer immunosurveillance: molecular mechanisms and prospects for therapy. Res. Rep. Biochem. 2015(5), 1–10 (2014).
  Google Scholar
• 12. Pollack SM, He Q, Yearley JH et al. T-cell infiltration and clonality correlate with programmed cell death protein 1 and programmed death-ligand 1 expression in patients with soft tissue sarcomas. Cancer 123(17), 3291–3304 (2017).
  Medline CASGoogle Scholar
• 13. Wagner MJ, Zhang Y, Cranmer LD et al. A phase 1/2 trial combining avelumab and trabectedin for advanced liposarcoma and leiomyosarcoma. Clin. Cancer Res. 28(11), 2306–2312 (2022).
  Medline CASGoogle Scholar
• 14. Toulmonde M, Brahmi M, Giraud A et al. Trabectedin plus durvalumab in patients with advanced pretreated soft tissue sarcoma and ovarian carcinoma (TRAMUNE): an open-label, multicenter phase Ib study. Clin. Cancer Res. 28(9), 1765–1772 (2021). (1078-0432.CCR-21–2258).
  Google Scholar
• 15. Italiano A, Bessede A, Pulido M et al. Pembrolizumab in soft-tissue sarcomas with tertiary lymphoid structures: a phase 2 PEMBROSARC trial cohort. Nat. Med. 28, 1199–1206 (2022).
  Medline CASGoogle Scholar
• 16. Chawla SP, Sankhala KK, Ravicz J et al. Clinical experience with combination chemo-/immunotherapy using trabectedin and nivolumab for advanced soft tissue sarcoma. Am. Soc. Clin. Oncol. 28, 1199–1206.
  Google Scholar
• 17. Gordon EM, Chua VS, Kim TT et al. A phase 2 study using ipilimumab, nivolumab, and trabectedin for previously untreated metastatic soft tissue sarcoma. J. Clin. Oncol. 39(Suppl. 15), 11562 (2021).
  Google Scholar
• 18. Pink D, Andreou D, Flörcken A et al. Efficacy and safety of nivolumab and trabectedin in pretreated patients with advanced soft tissue sarcomas (STS): preliminary results of a phase II trial of the German Interdisciplinary Sarcoma Group (GISG-15, NitraSarc) for the non-L sarcoma cohort. J. Clin. Oncol. 39(Suppl. 15), 11545 (2021). • A main ongoing trialevaluating the activity of trabectedin in combination with nivolumab.
  Google Scholar
• 19. Andtbacka RH, Kaufman HL, Collichio F et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J. Clin. Oncol. 33(25), 2780–2788 (2015).
  Medline CASGoogle Scholar
• 20. Chawla NS, Kim T, Sherman T et al. A phase 2 study of talimogene laherparepvec, nivolumab, and trabectedin (TNT) in advanced sarcoma. J. Clin. Oncol. 39(Suppl. 15), 11567 (2021).
  Google Scholar