Randomized Phase II Study of Nab-Paclitaxel and Gemcitabine With or Without Tocilizumab as First-Line Treatment in Advanced Pancreatic Cancer: Survival and Cachexia
dc.contributor.author | Chen, Inna M. | |
dc.contributor.author | Johansen, Julia S. | |
dc.contributor.author | Theile, Susann | |
dc.contributor.author | Silverman, Libbie M. | |
dc.contributor.author | Pelz, Katherine R. | |
dc.contributor.author | Madsen, Kasper | |
dc.contributor.author | Dajani, Olav | |
dc.contributor.author | Lim, Kevin Z. M. | |
dc.contributor.author | Lorentzen, Torben | |
dc.contributor.author | Gaafer, Omnia | |
dc.contributor.author | Koniaris, Leonidas G. | |
dc.contributor.author | Ferreira, Anna C. | |
dc.contributor.author | Neelon, Brian | |
dc.contributor.author | Guttridge, Denis C. | |
dc.contributor.author | Ostrowski, Michael C. | |
dc.contributor.author | Zimmers, Teresa A. | |
dc.contributor.author | Nielsen, Dorte | |
dc.contributor.department | Surgery, School of Medicine | |
dc.date.accessioned | 2025-07-17T15:45:33Z | |
dc.date.available | 2025-07-17T15:45:33Z | |
dc.date.issued | 2025 | |
dc.description.abstract | Purpose: This randomized phase-II trial (ClinicalTrials.gov identifier: NCT02767557) compared efficacy of gemcitabine/nab-paclitaxel (Gem/Nab) with or without the anti-interleukin-6 (IL-6) receptor antibody tocilizumab (Toc) for advanced pancreatic cancer (PC). Methods: A safety cohort received Gem 1,000 mg/m2 and Nab 125 mg/m2 on days 1, 8, and 15, and Toc 8 mg/kg on day 1 for each 28-day cycle. Participants with modified Glasgow prognostic scores of 1 or 2 were randomly assigned 1:1 to receive Gem/Nab/Toc or Gem/Nab. The primary end point was the overall survival (OS) rate at 6 months (OS6). Secondary end points were progression-free survival (PFS), overall response rate (ORR), and safety. Exploratory end points were cachexia, quality of life, and biomarkers, including the cachexia-promoting protein, growth differentiation factor 15 (GDF15). Results: Overall, 147 patients were treated, including six safety cohort participants. The median follow-up period was 8.1 months (IQR, 4.2-13.9). OS6 was 68.6% (95% CI, 56.3 to 78.1) for the Gem/Nab/Toc group and 62.0% (49.6-72.1) for the Gem/Nab group (P = .409). OS for Gem/Nab/Toc versus Gem/Nab improved at 18 months (27.1% v 7.0%, P = .001). No differences in median OS, PFS, or ORR were observed. Incidence of grade-3+ treatment-related adverse events (TrAEs) was 88.1% for Gem/Nab/Toc and 63.4% for Gem/Nab (P < .001). Gem/Nab/Toc decreased muscle loss versus Gem/Nab, with median change +0.1013% versus -3.430% (P = .0012) at 2 months and +0.7044 versus -3.353% (P = .036) at 4 months. Incidence of muscle loss was 43.48% on Gem/Nab/Toc versus 73.52% on Gem/Nab at 2 months (P = .0045) and 41.82% versus 68.75% (P = .0062) at 4 months. GDF15 was not changed by Gem/Nab or Gem/Nab/Toc. Conclusion: Although the primary end point was not met and TrAEs were increased by Toc, increased survival at 18 months and reduced muscle wasting support an anticachexia effect of IL-6 blockade independent of GDF15. Further studies could leverage these findings for precision anticachexia therapy. | |
dc.eprint.version | Final published version | |
dc.identifier.citation | Chen IM, Johansen JS, Theile S, et al. Randomized Phase II Study of Nab-Paclitaxel and Gemcitabine With or Without Tocilizumab as First-Line Treatment in Advanced Pancreatic Cancer: Survival and Cachexia. J Clin Oncol. 2025;43(18):2107-2118. doi:10.1200/JCO.23.01965 | |
dc.identifier.uri | https://hdl.handle.net/1805/49569 | |
dc.language.iso | en_US | |
dc.publisher | Wolters Kluwer | |
dc.relation.isversionof | 10.1200/JCO.23.01965 | |
dc.relation.journal | Journal of Clinical Oncology | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | en |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.source | PMC | |
dc.subject | Antineoplastic combined chemotherapy protocols | |
dc.subject | Deoxycytidine | |
dc.subject | Paclitaxel | |
dc.subject | Pancreatic neoplasms | |
dc.subject | Cachexia | |
dc.title | Randomized Phase II Study of Nab-Paclitaxel and Gemcitabine With or Without Tocilizumab as First-Line Treatment in Advanced Pancreatic Cancer: Survival and Cachexia | |
dc.type | Article |