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.authorChen, Inna M.
dc.contributor.authorJohansen, Julia S.
dc.contributor.authorTheile, Susann
dc.contributor.authorSilverman, Libbie M.
dc.contributor.authorPelz, Katherine R.
dc.contributor.authorMadsen, Kasper
dc.contributor.authorDajani, Olav
dc.contributor.authorLim, Kevin Z. M.
dc.contributor.authorLorentzen, Torben
dc.contributor.authorGaafer, Omnia
dc.contributor.authorKoniaris, Leonidas G.
dc.contributor.authorFerreira, Anna C.
dc.contributor.authorNeelon, Brian
dc.contributor.authorGuttridge, Denis C.
dc.contributor.authorOstrowski, Michael C.
dc.contributor.authorZimmers, Teresa A.
dc.contributor.authorNielsen, Dorte
dc.contributor.departmentSurgery, School of Medicine
dc.date.accessioned2025-07-17T15:45:33Z
dc.date.available2025-07-17T15:45:33Z
dc.date.issued2025
dc.description.abstractPurpose: 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.versionFinal published version
dc.identifier.citationChen 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.urihttps://hdl.handle.net/1805/49569
dc.language.isoen_US
dc.publisherWolters Kluwer
dc.relation.isversionof10.1200/JCO.23.01965
dc.relation.journalJournal of Clinical Oncology
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourcePMC
dc.subjectAntineoplastic combined chemotherapy protocols
dc.subjectDeoxycytidine
dc.subjectPaclitaxel
dc.subjectPancreatic neoplasms
dc.subjectCachexia
dc.titleRandomized Phase II Study of Nab-Paclitaxel and Gemcitabine With or Without Tocilizumab as First-Line Treatment in Advanced Pancreatic Cancer: Survival and Cachexia
dc.typeArticle
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