EP341/#510 Exploratory results of a phase IB trial of paclitaxel and carboplatin + galunisertib in patients with uterine and ovarian carcinosarcoma. (4th December 2022)

• Record Type: Journal Article
• Authors: Washington, Christina; Gunderson-Jackson, Camille; Walker, Joan; Mannel, Robert; Holman, Laura; Richardson, Debra; Neelakantan, Deepika; Cohoon, Andrew; Bhattacharya, Resham; Ding, Kai; Dwivedi, Shailendra; Gatalica, Zoran; Qian, Liangyue; Moxley, Katherine; Landrum, Lisa; Rowland, Michelle; Moore, Kathleen
• Is Part Of: International journal of gynecological cancer. Volume 32(2022)Supplement 3
• Page Start: A192
• Page End: A193
• Publication Date: 2022-12-04
• Subjects: Generative organs, Female -- Cancer -- Periodicals; 616.99465
• DOI: 10.1136/ijgc-2022-igcs.430
• Languages: English
• ISSNs: 1048-891X

Abstract

Abstract : Objectives: Gynecologic carcinosarcoma (CS) is a aggressive subtype of uterine and ovarian cancer with limited treatment options. Preclinical work demonstrates that transforming growth factor beta (TGF-β) may play a role in epithelial to mesenchymal transformation, a key feature in CS. This study aimed to determine the feasibility of combining Galunisertib (GB), a small molecule inhibitor of TGFβ receptor 1, with paclitaxel/carboplatin (TC) in patients with CS and evaluate upregulated pathways. Methods: Patients with newly diagnosed or recurrent CS were included. Intravenous TC was given every 28 days with GB 150 mg orally twice daily (Days 4–17). Feasibility was determined by the occurrence of dose limiting toxicity (DLT) during cycles 1–4. The exploratory objective was to determine whether H-score criteria of nuclear phospho-smad (pSMAD) levels after cycle 1 (C1) are associated with response to GB. Results: 26 patients were treated, with paired data for 6 patients. 81% were stage III/IV. 24/26 patients received 4 cycles of GB with TC. Of patients with measurable disease the ORR was 54%. Of patients with Stage III/IV disease the median PFS was 5.7 months. Among those with paired biopsies, there was no change in H-score pSMAD after C1 in 3/4 patients with a partial response. 4 patients with paired samples had a decrease in epithelial component, this did not correlate with response. Conclusions: GB was well tolerated with TC with no DLTs. Paired biopsies were too limited to make conclusions. However, the putative mechanism of action of galunisertib and the well tolerated nature of the combination would warrant further exploration.