Galunisertib plus gemcitabine vs. gemcitabine for first-line treatment of patients with unresectable pancreatic cancer
Open accessAbstract
Galunisertib is the first-in-class, first-in-human, oral small-molecule type I transforming growth factor-beta receptor (ALK5) serine/threonine kinase inhibitor to enter clinical development. The effect of galunisertib vs. placebo in patients with unresectable pancreatic cancer was determined. This was a two-part, multinational study: phase 1b was a non-randomised, open-label, multicentre, and dose-escalation study; phase 2 was a randomised, placebo- and Bayesian-augmented controlled, double-blind study in patients with locally advanced or metastatic pancreatic adenocarcinoma considered candidates for first-line chemotherapy with gemcitabine. Patients were randomised 2:1 to galunisertib–gemcitabine ( N = 104) or placebo-gemcitabine ( N = 52). Gemcitabine dose was 1000 mg/m 2 QW. Primary endpoints for phases 1b and 2, respectively, were phase 2 dose and overall survival. Secondary objectives included tolerability and biomarkers. Dose-escalation suggested a 300-mg/day dose. Primary objective was met: median survival times were 8.9 and 7.1 months for galunisertib and placebo, respectively (hazard ratio [HR] = 0.79 [95% credible interval: 0.59–1.09] and posterior probability HR < 1 = 0.93). Lower baseline biomarkers macrophage inflammatory protein-1-alpha and interferon-gamma-induced protein 10 were associated with galunisertib benefit. Galunisertib–gemcitabine combination improved overall survival vs. gemcitabine in patients with unresectable pancreatic cancer, with minimal added toxicity. Future exploration of galunisertib in pancreatic cancer is ongoing in combination with durvalumab.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
TGF-β released and activated by cancer cells, stromal fibroblasts, and/or immune cells dampens anti-tumor immunity and responses to immunotherapeutics through direct and indirect mechanisms.
“An underlying and predominant rationale focuses on the ability of TGF-β released and activated by cancer cells, stromal fibroblasts and/or immune cells to dampen anti-tumor immunity and responses to immunotherapeutics through direct and indirect mechanisms21,23,71,145,353,354.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [353]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Siegel, R. L., Miller, K. D., & Jemal, A. (2016) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21332 · Cited by 16,003 · see citing works
FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer
Conroy, T., Desseigne, F., Ychou, M., Bouché, O., Guimbaud, R., Bécouarn, Y., Adenis, A., Raoul, J.-L., Gourgou-Bourgade, S., de la Fouchardière, C., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1011923 · Cited by 7,810 · see citing works
Rahib, L., Smith, B. D., Aizenberg, R., Rosenzweig, A. B., Fleshman, J. M., & Matrisian, L. M. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-0155 · Cited by 7,094 · see citing works
Increased Survival in Pancreatic Cancer with nab-Paclitaxel plus Gemcitabine
Von Hoff, D. D., Ervin, T., Arena, F. P., Chiorean, E. G., Infante, J., Moore, M., Seay, T., Tjulandin, S. A., Ma, W. W., Saleh, M. N., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1304369 · Cited by 6,712 · see citing works
Self-citationBurris, H. A., Moore, M. J., Andersen, J., Green, M. R., Rothenberg, M. L., Modiano, M., Cripps, M. C., Portenoy, R. K., Storniolo, A. M., Tarassoff, P. G., et al. (1997) · Journal of Clinical Oncology · doi:10.1200/jco.1997.15.6.2403 · Cited by 5,895 · see citing works
Massagué, J. (2008) · Cell · doi:10.1016/j.cell.2008.07.001 · Cited by 3,907 · see citing works
Genomic analyses identify molecular subtypes of pancreatic cancer
Bailey, P., Chang, D. K., Nones, K., Johns, A. L., Patch, A.-M., Gingras, M.-C., Miller, D. K., Christ, A. N., Bruxner, T. J. C., Quinn, M. C., et al. (2016) · Nature · doi:10.1038/nature16965 · Cited by 3,621 · see citing works
TGF-β Activation and Function in Immunity
Travis, M. A., & Sheppard, D. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120257 · Cited by 856 · see citing works
Lahn, M. M. F., Herbertz, S., Sawyer, J. S., Stauber, A. J., Gueorguieva, I., Driscoll, K. E., Estrem, S. T., Cleverly, A., Desaiah, D., Guba, S. C., et al. (2015) · Drug Design Development and Therapy · doi:10.2147/dddt.s86621 · Cited by 558 · see citing works
Self-citationMetastatic Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline
Sohal, D. P. S., Mangu, P. B., Khorana, A. A., Shah, M. A., Philip, P. A., O'Reilly, E. M., Uronis, H. E., Ramanathan, R. K., Crane, C. H., Engebretson, A., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.67.1412 · Cited by 331 · see citing works
Melisi, D., Ishiyama, S., Sclabas, G. M., Fleming, J. B., Xia, Q., Tortora, G., Abbruzzese, J. L., & Chiao, P. J. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-07-0337 · Cited by 324 · see citing works
Self-citationSideras, K., Braat, H., Kwekkeboom, J., van Eijck, C. H. J., Peppelenbosch, M. P., Sleijfer, S., & Bruno, M. J. (2013) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2013.11.005 · Cited by 174 · see citing works
Tamburrino, A., Piro, G., Carbone, C., Tortora, G., & Melisi, D. (2013) · Frontiers in Pharmacology · doi:10.3389/fphar.2013.00056 · Cited by 101 · see citing works
Self-citationPeixoto, R. D., Ho, M., Renouf, D. J., Lim, H. J., Gill, S., Ruan, J. Y., & Cheung, W. Y. (2015) · American Journal of Clinical Oncology · doi:10.1097/coc.0000000000000193 · Cited by 86 · see citing works
Metastatic pancreatic cancer: Is there a light at the end of the tunnel?
Vaccaro, V. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i16.4788 · Cited by 62 · see citing works
Piro, G., Simionato, F., Carbone, C., et al. (2017) · OncoImmunology · doi:10.1080/2162402x.2017.1322242 · Cited by 55 · see citing works
Pancreatic Cancer: Systemic Combination Therapies for a Heterogeneous Disease
Melisi, D., Calvetti, L., Frizziero, M., et al. (2014) · Current Pharmaceutical Design · doi:10.2174/1381612820666140826154327 · Cited by 35 · see citing works
Self-citationGiannelli, G., Faivre, S. J., Santoro, A., et al. (2014) · Journal of Hepatology · doi:10.1016/s0168-8278(14)60128-8 · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Transforming Growth Factor-β Signaling in Immunity and Cancer
Batlle, E., & Massagué, J. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.024 · Cited by 2,366 · see citing works
Mao, X., Xu, J., Wang, W., Liang, C., Hua, J., Liu, J., Zhang, B., Meng, Q., Yu, X., & Shi, S. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01428-1 · Cited by 2,290 · see citing works
TGFβ biology in cancer progression and immunotherapy
Derynck, R., Turley, S. J., & Akhurst, R. J. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0403-1 · Cited by 944 · see citing works
Novel therapies emerging in oncology to target the TGF‐β pathway
Kim, B.-G., Malek, E., Choi, S. H., Ignatz-Hoover, J. J., & Driscoll, J. J. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01053-x · Cited by 453 · see citing works
Targeting TGFβ signal transduction for cancer therapy
Liu, S., Ren, J., & ten Dijke, P. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00436-9 · Cited by 413 · see citing works
“Phase 1/2 clinical trials of this inhibitor for patients with metastatic prostate cancer/TNBC/ advanced HCC/rectal cancer/recurrent glioblastoma are ongoing.(213,215,216) A phase 2 study of this inhibitor for patients with advanced HCC showed acceptable safety and prolonged overall survival.”
BackgroundPancreatic cancer evolution and heterogeneity: integrating omics and clinical data
Connor, A. A., & Gallinger, S. (2022) · Nature Reviews Cancer · doi:10.1038/s41568-021-00418-1 · Cited by 369 · see citing works
Tumor cell plasticity in targeted therapy-induced resistance: Mechanisms and new strategies
Shi, Z.-D., Pang, K., Wu, Z.-X., Dong, Y., Hao, L., Qin, J.-X., Wang, W., Chen, Z.-S., & Han, C.-H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01383-x · Cited by 256 · see citing works
Lind, H., Gameiro, S. R., Jochems, C., Donahue, R. N., Strauss, J., Gulley, J. L., Palena, C., & Schlom, J. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2019-000433 · Cited by 247 · see citing works
Martin, C. J., Datta, A., Littlefield, C., Kalra, A., Chapron, C., Wawersik, S., Dagbay, K. B., Brueckner, C. T., Nikiforov, A., Danehy, F. T., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aay8456 · Cited by 224 · see citing works
Impairment of NKG2D-Mediated Tumor Immunity by TGF-β
Lazarova, M., & Steinle, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02689 · Cited by 149 · see citing works
Determinants and functions of CAFs secretome during cancer progression and therapy
Linares, J., Marín-Jiménez, J. A., Badia-Ramentol, J., & Calon, A. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.621070 · Cited by 110 · see citing works
Metropulos, A. E., Munshi, H. G., & Principe, D. R. (2022) · eBioMedicine · doi:10.1016/j.ebiom.2022.104380 · Cited by 81 · see citing works
- Authors
- Melisi, D., Garcia-Carbonero, R., Macarulla, T., Pezet, D., Deplanque, G., Fuchs, M., Trojan, J., Oettle, H., Kozloff, M., Cleverly, A., Smith, C., Estrem, S. T., Gueorguieva, I., Lahn, M. M. F., Blunt, A., Benhadji, K. A., & Tabernero, J.
- Affiliations
- University of Verona (IT)
- Centro de Investigación Biomédica en Red de Cáncer (ES)
- Centre Hospitalier Universitaire de Clermont-Ferrand (FR)
- Hôpital Riviera-Chablais (CH)
- München Klinik Bogenhausen (DE)
- Ingalls Memorial Hospital (US)
- Eli Lilly (United Kingdom) (GB)
- Eli Lilly (United States) (US)
- Advaxis (United States) (US)
- Universitat Autònoma de Barcelona (ES)
- Corresponding author
- Melisi, Davide
- ORCID
- Venue
- British Journal of Cancer
- Published
- 2018-10-15
- Volume
- 119
- Issue
- 10
- Pages
- 1208-1214
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC6251034
- OpenAlex
- W2896652675
- Cited by
- 294
- References
- 18
- Citations by year
- 2026: 30 · 2025: 38 · 2024: 36 · 2023: 37 · 2022: 43 · 2021: 61 · 2020: 37 · 2019: 12
- FWCI
- 10.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- British Journal of Cancer (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Funders
- Eli Lilly and Company
- Associazione Italiana per la Ricerca sul Cancro (19111)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
- Keywords
- galunisertib, gemcitabine, unresectable pancreatic cancer, pancreatic ductal adenocarcinoma, first-line chemotherapy, overall survival, biomarkers, macrophage inflammatory protein-1alpha, CXCL10, dose escalation
- MeSH terms
- Gemcitabine, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Deoxycytidine, Dose-Response Relationship, Drug, Female, Humans, Male, Middle Aged, Pancreatic Neoplasms, Placebos, Pyrazoles, Quinolines, Biomarkers, Tumor, Signal Transduction, Transforming Growth Factor beta
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
