IGF-1 axis changes with ADT and docetaxel in metastatic prostate cancer

in Endocrine-Related Cancer
Authors:
Praful Ravi Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

Search for other papers by Praful Ravi in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0002-7466-4702
,
Victoria Wang Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

Search for other papers by Victoria Wang in
Current site
Google Scholar
PubMed
Close
,
Raina N Fichorova Department of Obstetrics, Gynecology and Reproductive Biology, Brigham & Women’s Hospital, Boston, Massachusetts, USA

Search for other papers by Raina N Fichorova in
Current site
Google Scholar
PubMed
Close
,
Bradley McGregor Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

Search for other papers by Bradley McGregor in
Current site
Google Scholar
PubMed
Close
,
Xiao X Wei Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

Search for other papers by Xiao X Wei in
Current site
Google Scholar
PubMed
Close
,
Shehzad Basaria Division of Endocrinology, Diabetes and Hypertension, Brigham & Women’s Hospital, Boston, Massachusetts, USA

Search for other papers by Shehzad Basaria in
Current site
Google Scholar
PubMed
Close
, and
Christopher J Sweeney South Australian Immunogenomics Cancer Institute, University of Adelaide, Adelaide, Australia

Search for other papers by Christopher J Sweeney in
Current site
Google Scholar
PubMed
Close

Correspondence should be addressed to P Ravi: praful_ravi@dfci.harvard.edu
Restricted access
Rent on DeepDyve

Sign up for journal news

Androgen deprivation therapy (ADT) forms the cornerstone of treatment in locally advanced and metastatic prostate cancer (PCa). Since the growth hormone–insulin-like growth factor (GH–IGF-1) axis has been implicated in prostate tumorigenesis, we aimed to evaluate the association between IGF-1 and its binding proteins on outcomes in men with metastatic PCa treated with ADT, with or without docetaxel (D). We analyzed serum samples for IGF-1 and its family proteins from baseline, 6 months post-randomization, and at the time of progression in men enrolled to receive ADT +/− D in the phase 3 CHAARTED trial. The key outcomes were time to the development of castrate-resistant prostate cancer and overall survival (OS). About 560 patients had samples available for analysis. At 6 months, significant increases in IGF-BP1 (mean Δ+27.4%, P = 0.033), IGF-BP3 (mean Δ+10.3%, P < 0.001), and IGF-BP4 (mean Δ+31.1%, P < 0.001) were seen in the ADT + D group, while the ADT group showed an increase in IGF-BP3 (mean Δ+5.5%, P = 0.015). A higher IGF-1:IGF-BP1 ratio at baseline and after 6 months was associated with improved OS in both the ADT (baseline: hazard ratio (HR) = 0.77, P = 0.026; 6 months: HR = 0.83, P = 0.036) and ADT + D groups (baseline: HR = 0.78, P = 0.04; 6 months: HR = 0.81, P = 0.018). Patients with a log10IGF-1:IGF-BP1 ratio >1.3 at baseline had improved OS when meta-analyzed with data from a prior cohort (HR = 0.71). A higher baseline and 6-month IGF-1:IGF-BP1 ratio was associated with better OS. Further exploration of the IGF-1 axis will be important to assess its role as a predictive biomarker and to target this axis in therapeutic trials.

Supplementary Materials

 

  • Collapse
  • Expand
  • Barata P, Cooney M, Tyler A, Wright J, Dreicer R & & Garcia JA 2018 A phase 2 study of OSI-906 (linsitinib, an insulin-like growth factor receptor-1 inhibitor) in patients with asymptomatic or mildly symptomatic (non-opioid requiring) metastatic castrate resistant prostate cancer (CRPC). Investigational New Drugs 36 451457. (https://doi.org/10.1007/s10637-018-0574-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, Coskinas X, Frydenberg M, Hague WE, Horvath LG, et al.2019 Enzalutamide with standard first-line therapy in metastatic prostate cancer. New England Journal of Medicine 381 121131. (https://doi.org/10.1056/NEJMoa1903835)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • DiGiovanni J, Kiguchi K, Frijhoff A, Wilker E, Bol DK, Beltran L, Moats S, Ramirez A, Jorcano J & & Conti C 2000 Deregulated expression of insulin-like growth factor 1 in prostate epithelium leads to neoplasia in transgenic mice. Proceedings of the National Academy of Sciences of the United States of America 97 34553460. (https://doi.org/10.1073/pnas.97.7.3455)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Durai R, Davies M, Yang W, Yang SY, Seifalian A, Goldspink G & & Winslet M 2006 Biology of insulin-like growth factor binding protein-4 and its role in cancer (review). International Journal of Oncology 28 13171325. (https://doi.org/10.3892/ijo.28.6.1317)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fizazi K, Foulon S, Carles J, Roubaud G, Mcdermott R, Flechon A, Tombal B, Supiot S, Berthold D, Ronchin P, et al.2022 Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 x 2 factorial design. Lancet 399 16951707. (https://doi.org/10.1016/S0140-6736(2200367-1)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Harshman LC, Chen YH, Liu G, Carducci MA, Jarrard D, Dreicer R, Hahn N, Garcia JA, Hussain M, Shevrin D, et al.2018 Seven-month prostate-specific antigen is prognostic in metastatic hormone-sensitive prostate cancer treated with androgen deprivation with or without docetaxel. Journal of Clinical Oncology 36 376382. (https://doi.org/10.1200/JCO.2017.75.3921)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Inman BA, Harel F, Audet JF, Meyer F, Douville P, Fradet Y & & Lacombe L 2005 Insulin-like growth factor binding protein 2: an androgen-dependent predictor of prostate cancer survival. European Urology 47 695702. (https://doi.org/10.1016/j.eururo.2004.12.015)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • James ND, De Bono JS, Spears MR, Clarke NW, Mason MD, Dearnaley DP, Ritchie AWS, Amos CL, Gilson C, Jones RJ, et al.2017 Abiraterone for prostate cancer not previously treated with hormone therapy. New England Journal of Medicine 377 338351. (https://doi.org/10.1056/NEJMoa1702900)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kyriakopoulos CE, Chen YH, Carducci MA, Liu G, Jarrard DF, Hahn NM, Shevrin DH, Dreicer R, Hussain M, Eisenberger M, et al.2018 Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized Phase III E3805 CHAARTED trial. Journal of Clinical Oncology 36 10801087. (https://doi.org/10.1200/JCO.2017.75.3657)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Matsubara N, Chi KN, Ozguroglu M, Rodriguez-Antolin A, Feyerabend S, Fein L, Alekseev BY, Sulur G, Protheroe A, Li S, et al.2020 Correlation of prostate-specific antigen kinetics with overall survival and radiological progression-free survival in metastatic castration-sensitive prostate cancer treated with abiraterone acetate plus prednisone or placebos added to androgen deprivation therapy: post hoc analysis of Phase 3 LATITUDE study. European Urology 77 494500. (https://doi.org/10.1016/j.eururo.2019.11.021)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pollak M 2012 The insulin and insulin-like growth factor receptor family in neoplasia: an update. Nature Reviews. Cancer 12 159169. (https://doi.org/10.1038/nrc3215)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Qian F & & Huo D 2020 Circulating insulin-like growth Factor-1 and risk of total and 19 site-specific cancers: cohort study analyses from the UK Biobank. Cancer Epidemiology, Biomarkers and Prevention 29 23322342. (https://doi.org/10.1158/1055-9965.EPI-20-0743)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Riaz IB, Naqvi SAA, He H, Asghar N, Siddiqi R, Liu H, Singh P, Childs DS, Ravi P, Hussain SA, et al.2023 First-line systemic treatment options for metastatic castration-sensitive prostate cancer: a living systematic review and network meta-analysis. JAMA Oncology 9. (https://doi.org/10.1001/jamaoncol.2022.7762)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sharma J, Gray KP, Evan C, Nakabayashi M, Fichorova R, Rider J, Mucci L, Kantoff PW & & Sweeney CJ 2014a Elevated insulin-like growth factor binding protein-1 (IGFBP-1) in men with metastatic prostate cancer starting androgen deprivation therapy (ADT) is associated with shorter time to castration resistance and overall survival. Prostate 74 225234. (https://doi.org/10.1002/pros.22744)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sharma J, Gray KP, Harshman LC, Evan C, Nakabayashi M, Fichorova R, Rider J, Mucci L, Kantoff PW & & Sweeney CJ 2014b Elevated IL-8, TNF-alpha, and MCP-1 in men with metastatic prostate cancer starting androgen-deprivation therapy (ADT) are associated with shorter time to castration-resistance and overall survival. Prostate 74 820828. (https://doi.org/10.1002/pros.22788)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Smith MR, Hussain M, Saad F, Fizazi K, Sternberg CN, Crawford ED, Kopyltsov E, Park CH, Alekseev B, Montesa-Pino Á, et al.2022 Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. New England Journal of Medicine 386 11321142. (https://doi.org/10.1056/NEJMoa2119115)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, Wong YN, Hahn N, Kohli M, Cooney MM, et al.2015 Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. New England Journal of Medicine 373 737746. (https://doi.org/10.1056/NEJMoa1503747)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Watts EL, Goldacre R, Key TJ, Allen NE, Travis RC & & Perez-Cornago A 2020 Hormone-related diseases and prostate cancer: an English national record linkage study. International Journal of Cancer 147 803810. (https://doi.org/10.1002/ijc.32808)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wu JD, Haugk K, Woodke L, Nelson P, Coleman I & & Plymate SR 2006 Interaction of IGF signaling and the androgen receptor in prostate cancer progression. Journal of Cellular Biochemistry 99 392401. (https://doi.org/10.1002/jcb.20929)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yu EY, Li H, Higano CS, Agarwal N, Pal SK, Alva A, Heath EI, Lam ET, Gupta S, Lilly MB, et al.2015 SWOG S0925: a randomized Phase II study of androgen deprivation combined with cixutumumab versus androgen deprivation alone in patients with new metastatic hormone-sensitive prostate cancer. Journal of Clinical Oncology 33 16011608. (https://doi.org/10.1200/JCO.2014.59.4127)

    • PubMed
    • Search Google Scholar
    • Export Citation