@article{01JW5AEEYN71NTRMMSKP84J9G7,
  abstract     = {{Introduction: Pressurized intraperitoneal aerosol chemotherapy-oxaliplatin (PIPAC-OX) induces direct DNA damage and immunogenic cell death in patients with gastric cancer peritoneal metastases (GCPM). Combining PIPAC-OX with immune checkpoint inhibition remains untested. We conducted a phase I first-in-human trial evaluating the safety and efficacy of PIPAC-OX combined with systemic nivolumab (NCT03172416). Methods: Patients with GCPM who experienced disease progression on at least first-line systemic therapy were recruited across three centers in Singapore and Belgium. Patients received PIPAC-OX at 90 mg/m(2) every 6 weeks and i.v. nivolumab 240 mg every 2 weeks. Translational studies were carried out on GCPM samples acquired during PIPAC-OX procedures. Results: In total, 18 patients with GCPM were prospectively recruited. The PIPAC-OX and nivolumab combination was well tolerated with manageable treatment-related adverse events, although one patient suffered from grade 4 vomiting. At second and third PIPAC-OX, respectively, the median decrease in peritoneal cancer index (PCI) was -5 (interquartile range: -12 to +1) and -7 (interquartile range: -6 to -20) and peritoneal regression grade 1 or 2 was observed in 66.7% (6/9) and 100% (3/3). Translational analyses of 43 GCPM samples revealed enrichment of immune/stromal infiltration and inflammatory signatures in peritoneal tumors after PIPAC-OX and nivolumab. M2 macrophages were reduced in treated peritoneal tumor samples while memory CD4+, CD8+ central memory and naive CD8+ T-cells were increased. Conclusions: The first-in-human trial combining PIPAC-OX and nivolumab demonstrated safety and tolerability, coupled with enhanced T-cell infiltration within peritoneal tumors. This trial sets the stage for future combinations of systemic immunotherapy with locoregional intraperitoneal treatments.}},
  articleno    = {{103681}},
  author       = {{Sundar, R. and Chia, D.K.A. and Zhao, J.J. and Lee, A.R.Y.B. and Kim, G. and Tan, H.L. and Pang, A. and Shabbir, A. and Willaert, Wouter and Ma, H. and Huang, K.K. and Hagihara, T. and Tan, A.L.K. and Ong, C.-A.J. and Wong, J.S.M. and Seo, C.J. and Walsh, R. and Chan, G. and Cheo, S.W. and Soh, C.C.C. and Callebout, Eduard and Geboes, Karen and Ng, M.C.H. and Lum, J.H.Y. and Leow, W.Q. and Selvarajan, S. and Hoorens, Anne and Ang, W.H. and Pang, H. and Tan, P. and Yong, W.P. and Chia, C.S.L. and Ceelen, Wim and So, J.B.Y.}},
  issn         = {{2059-7029}},
  journal      = {{ESMO OPEN}},
  keywords     = {{immunotherapy,locoregional therapy,PIPAC,tumor microenvironment,gastric cancer,intraperitoneal,peritoneal metastases,peritoneum,niche,AEROSOL CHEMOTHERAPY PIPAC,PLUS CHEMOTHERAPY,CARCINOMATOSIS,CELLS}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{11}},
  title        = {{Phase I PIANO trial—PIPAC-oxaliplatin and systemic nivolumab combination for gastric cancer peritoneal metastases : clinical and translational outcomes}},
  url          = {{http://doi.org/10.1016/j.esmoop.2024.103681}},
  volume       = {{9}},
  year         = {{2024}},
}

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