American Association for Cancer Research
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Supplementary Figure 5 from Phase II window study of olaparib alone or with cisplatin or durvalumab in operable Head and Neck Cancer

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journal contribution
posted on 2023-07-17, 15:00 authored by Myrto Moutafi, Georgia-Angeliki Koliou, George Papaxoinis, Panagiota Economopoulou, Ioannis Kotsantis, Maria Gkotzamanidou, Maria Anastasiou, Dimitrios Pectasides, Efthymios Kyrodimos, Alexander Delides, Evangelos Giotakis, Nikolaos G. Papadimitriou, Ioannis G. Panayiotides, Christos Perisanidis, Aileen I. Fernandez, Vasiliki Xirou, Christos Poulios, Eleni Gagari, Vesal Yaghoobi, Niki Gavrielatou, Saba Shafi, Thazin Nwe Aung, Andromachi Kougioumtzopoulou, Vassilis Kouloulias, Konstantinos Palialexis, Stavros Gkolfinopoulos, Areti Strati, Evi Lianidou, George Fountzilas, David L. Rimm, Periklis G. Foukas, Amanda Psyrri

Supplementary Figure 5. Map showing the distribution of mutations per gene per tumor. Light and dark purple, green and orange indicate pre- and post-treatment samples for patients treated with cisplatin and olaparib, olaparib and durvalumab and olaparib only, respectively. Blues correspond to samples before and after second biopsy/surgery for patients who did not receive treatment.



Purpose:We conducted a phase II randomized non-comparative window of opportunity trial to evaluate the inhibition of cellular proliferation and the modulation of immune microenvironment after treatment with Olaparib alone or in combination with Cisplatin or Durvalumab in operable Head and Neck Squamous Cell Carcinoma (HNSCC) patients. Patients and Methods:Forty-one HNSCC patients were randomized to Cisplatin plus Olaparib (Arm A), Olaparib alone (Arm B), no treatment (Arm C) or Durvalumab plus Olaparib (Arm D). The primary endpoint was to evaluate the percentage of patients in each arm that achieved a reduction of at least 25% in Ki67. Secondary endpoints included objective response rate (ORR), safety and pathologic complete response rate (pCR). Paired baseline and resection tumor biopsies and blood samples were evaluated for pre-specified biomarkers. Results:A decrease in Ki67 of at least 25% was observed in 44.8% of treated patients, as measured by quantitative immunofluorescence (QIF). The ORR among treated patients was 12.1%. pCR was observed in 2 patients. Two serious adverse events occurred in 2 patients. PD-L1 levels were significantly higher after treatment in arms (A) and (D). Expression of CD163 and Colony Stimulating Factor 1 Receptor (CSF1R) genes, markers of M2 macrophages, increased significantly posttreatment whereas the expression of CD80 a marker of M1 macrophages decreased. Conclusions:Preoperative Olaparib with Cisplatin or alone or with Durvalumab was safe in the preoperative setting and led to decrease in Ki67 in 44.8% of treated patients. Olaparib-based treatment modulates the tumor microenvironment leading to PD-L1 upregulation and induction of pro-tumor features of macrophages.