A phase Ib/II study of regorafenib and paclitaxel in patients with beyond first-line advanced esophagogastric carcinoma (REPEAT)
| Autor: | Charlotte I Stroes, Sandor Schokker, Mohammed Khurshed, Stephanie O van der Woude, Ron AA Mathôt, Marije Slingerland, Judith de Vos-Geelen, Massimo Zucchetti, Cristina Matteo, Erik van Dijk, Bauke Ylstra, Victor Thijssen, Sarah Derks, Tesfay Godefa, Willemieke Dijksterhuis, Gerben E Breimer, Otto M van Delden, Rob HA Verhoeven, Sybren L Meijer, Maarten F Bijlsma, Hanneke WM van Laarhoven |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Therapeutic Advances in Medical Oncology, Vol 14 (2022) |
| Druh dokumentu: | article |
| ISSN: | 1758-8359 17588359 |
| DOI: | 10.1177/17588359221109196 |
| Popis: | Purpose: Regorafenib monotherapy, a multikinase inhibitor of angiogenesis, tumor microenvironment, and tumorigenesis, showed promising results in gastric cancer. We aimed to assess the tolerability of regorafenib and paclitaxel in patients with advanced esophagogastric cancer (EGC) refractory to first-line treatment, and explore potential biomarkers. Methods: Patients received paclitaxel (80 mg/m 2 ) on days 1, 8, and 15 of a 28-day cycle and regorafenib (80/120/160 mg) on days 1–21 in the dose-escalation cohort, and the maximum-tolerated dose (MTD) in the dose-expansion cohort. Exploratory, overall survival (OS) and progression-free survival (PFS) were compared to a propensity-score matched cohort receiving standard second-/third-line systemic treatment. Paclitaxel pharmacokinetics were assessed using samples from day 1 (D1) and day 15 (D15). We performed enzyme-linked immunosorbent assay measurements of galectin-1, RNA sequencing, and shallow whole-genome sequencing of metastatic tumor biopsies for biomarker analyses. Results: In the dose-escalation cohort ( n = 14), the MTD of regorafenib was 120 mg. In all, 34 patients were enrolled in the dose-expansion cohort. Most common toxicities (all grades; grade ⩾ 3) were fatigue (79%; 4%) and sensory neuropathy (63%; 4%). Best responses achieved were partial response (28%) and stable disease (54%). Median OS and PFS were 7.8 and 4.2 months, respectively (median follow-up: 7.8 months). OS ( p = 0.08) and PFS ( p = 0.81) were not significantly improved compared to the matched cohort. Paclitaxel concentrations were significantly increased with regorafenib (D15) compared with paclitaxel only (D1; p |
| Databáze: | Directory of Open Access Journals |
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