Outcomes of older men receiving docetaxel for metastatic hormone-sensitive prostate cancer

Daniel E Lage, M Dror Michaelson, Richard J Lee, Joseph A Greer, Jennifer S Temel, Christopher J Sweeney, Daniel E Lage, M Dror Michaelson, Richard J Lee, Joseph A Greer, Jennifer S Temel, Christopher J Sweeney

Abstract

Background: Most men who die of prostate cancer are older than 70 years. The ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) randomized men of all ages with metastatic hormone-sensitive prostate cancer (mHSPC) to receive androgen deprivation therapy (ADT) with or without docetaxel demonstrating an overall survival (OS) benefit for docetaxel.

Methods: In a post-hoc analysis of this trial, we assessed patient characteristics and OS in patients ≥70 years ("older men") versus <70 years ("younger men") with Cox proportional hazards models. In addition, we compared adverse events, therapy completion rate, and subsequent treatment patterns between these two groups using Chi-squared tests.

Results: 177 (22.4%) patients were ≥70 years. Docetaxel + ADT resulted in improved OS in both older and younger men (Hazard Ratio [HR] 0.45, 95%CI: 0.25-0.80 for older men; HR 0.71, 95%CI: 0.53-0.95 for younger men). This treatment benefit was seen for subgroups of older men with high volume disease (HR 0.43, 95%CI 0.23-0.79) and de novo metastatic disease (HR 0.36, 95%CI 0.19-0.69). A similar proportion of older and younger men completed six cycles of docetaxel (82.6% vs. 87.1%, p = 0.28). Rates of grade 3-5 adverse events were similar between older and younger men (36.8% vs. 26.8%, respectively, p = 0.069). The rate of any Grades 4-5 adverse events did not differ significantly between older and younger men (14.9% vs. 11.9%, respectively, p = 0.46). In the control arm, a smaller proportion of older men received subsequent cancer treatments (34.4% vs. 51.5%, p = 0.017) or subsequent docetaxel (25.6% vs. 37.6%, p = 0.035) compared to younger men.

Conclusions: Older men with mHSPC had similar OS benefit and clinical outcomes compared to younger men when receiving docetaxel + ADT. Oncologists should consider docetaxel chemotherapy as a favorable treatment option for older men with mHSPC who are fit for chemotherapy.

Trial registration: ClinicalTrials.gov NCT00309985.

© 2021. The Author(s), under exclusive licence to Springer Nature Limited.

Figures

Figure 1:
Figure 1:
Overall Survival, by Age (Age

Figure 2:

Overall Survival, by Age (Age…

Figure 2:

Overall Survival, by Age (Age >= 70)

Figure 2:
Overall Survival, by Age (Age >= 70)

Figure 3:

Overall Survival, by Age and…

Figure 3:

Overall Survival, by Age and Other Clinical Features

Figure 3:
Overall Survival, by Age and Other Clinical Features
Figure 2:
Figure 2:
Overall Survival, by Age (Age >= 70)
Figure 3:
Figure 3:
Overall Survival, by Age and Other Clinical Features

References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. Ca Cancer J Clin. 2019;69(1):7–34. doi:10.3322/caac.21551
    1. National Cancer Institute. Cancer Stat Facts: Prostate Cancer. National Cancer Institute Surveillance, Epidemiology, and End Results Program. Published n.d. Accessed April 30, 2020.
    1. Bernard B, Burnett C, Sweeney CJ, Rider JR, Sridhar SS. Impact of age at diagnosis of de novo metastatic prostate cancer on survival. Cancer. Published online 2019. doi:10.1002/cncr.32630
    1. James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Spears MR, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387(10024):1163–1177. doi:10.1016/s0140-6736(15)01037-5
    1. Sweeney CJ, Chen Y-H, Carducci M, Liu G, Jarrard DF, Eisenberger M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. New Engl J Medicine. 2015;373(8):737–746. doi:10.1056/nejmoa1503747
    1. Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. New Engl J Medicine. 2017;377(4):352–360. doi:10.1056/nejmoa1704174
    1. James ND, Bono JS de, Spears MR, Clarke NW, Mason MD, Dearnaley DP, et al. Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. New Engl J Medicine. 2017;377(4):338–351. doi:10.1056/nejmoa1702900
    1. Chi KN, Agarwal N, Bjartell A, Chung BH, Gomes AJP de S, Given R, et al. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. New Engl J Med. 2019;381(1):13–24. doi:10.1056/nejmoa1903307
    1. Armstrong AJ, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Azad A, et al. ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol Official J Am Soc Clin Oncol. 2019;37(32):2974–2986. doi:10.1200/jco.19.00799
    1. Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, et al. Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. New Engl J Med. 2019;381(2):121–131. doi:10.1056/nejmoa1903835
    1. VanderWeele DJ, Antonarakis ES, Carducci MA, Dreicer R, Fizazi K, Gillessen S, et al. Metastatic Hormone-Sensitive Prostate Cancer: Clinical Decision Making in a Rapidly Evolving Landscape of Life-Prolonging Therapy. J Clin Oncol Official J Am Soc Clin Oncol. 2019;37(32):2961–2967. doi:10.1200/jco.19.01595
    1. Repetto L, Fratino L, Audisio RA, Venturino A, Gianni W, Vercelli M, et al. Comprehensive geriatric assessment adds information to Eastern Cooperative Oncology Group performance status in elderly cancer patients: an Italian Group for Geriatric Oncology Study. J Clin Oncol. 2002;20(2):494–502. doi:10.1200/jco.2002.20.2.494
    1. DuMontier C, Loh KP, Bain PA, Silliman RA, Abel GA, Djulbegovic B, et al. Defining undertreatment and overtreatment in older patients with cancer: A scoping review of the literature. J Clin Oncol. 2019;37(15_suppl):e23020–e23020. doi:10.1200/jco.2019.37.15_suppl.e23020
    1. Hurria A, Gupta S, Zauderer M, Zuckerman EL, Cohen HJ, Muss H, et al. Developing a cancer-specific geriatric assessment. Cancer. 2005;104(9):1998–2005. doi:10.1002/cncr.21422
    1. Mohile SG, Dale W, Somerfield MR, Schonberg MA, Boyd CM, Burhenn PS, et al. Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy: ASCO Guideline for Geriatric Oncology. J Clin Oncol. 2018;36(22):2326–2347. doi:10.1200/jco.2018.78.8687
    1. Mohile SG, Epstein RM, Hurria A, Heckler CE, Canin B, Culakova E, et al. Communication With Older Patients With Cancer Using Geriatric Assessment. Jama Oncol. 2020;6(2):1. doi:10.1001/jamaoncol.2019.4728
    1. Hurria A, Mohile S, Gajra A, Klepin H, Muss H, Chapman A, et al. Validation of a Prediction Tool for Chemotherapy Toxicity in Older Adults With Cancer. J Clin Oncol. 2016;34(20):2366–2371. doi:10.1200/jco.2015.65.4327
    1. Kyriakopoulos CE, Chen Y-H, Carducci MA, Liu G, Jarrard DF, Hahn NM, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial. J Clin Oncol. 2018;36(11):JCO.2017.75.365. doi:10.1200/jco.2017.75.3657
    1. Gordon LG, Walker SM, Mervin MC, Lowe A, Smith DP, Gardiner RA, et al. Financial toxicity: a potential side effect of prostate cancer treatment among Australian men. Eur J Cancer Care. 2017;26(1):e12392. doi:10.1111/ecc.12392
    1. Tsao PA, Caram MEV. Factors to Guide Treatment Selection for Hormone-Sensitive Metastatic Prostate Cancer. Cancer J. 2020;26(1):76–82. doi:10.1097/ppo.0000000000000423
    1. Tannock IF, Wit R de, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus Prednisone or Mitoxantrone plus Prednisone for Advanced Prostate Cancer. New Engl J Med. 2004;351(15):1502–1512. doi:10.1056/nejmoa040720
    1. Scott JM, Stene G, Edvardsen E, Jones LW. Performance Status in Cancer: Not Broken, But Time for an Upgrade? J Clin Oncol Official J Am Soc Clin Oncol. Published online 2020:JCO2000721. doi:10.1200/jco.20.00721
    1. Cohen HJ, Smith D, Sun C-L, Tew W, Mohile SG, Owusu C, et al. Frailty as determined by a comprehensive geriatric assessment-derived deficit-accumulation index in older patients with cancer who receive chemotherapy. Cancer. 2016;122(24). doi:10.1002/cncr.30269
    1. Singh H, Kanapuru B, Smith C, Fashoyin-Aje LA, Myers A, Kim G, et al. FDA analysis of enrollment of older adults in clinical trials for cancer drug registration: A 10-year experience by the U.S. Food and Drug Administration. J Clin Oncol. 2017;35(15_suppl):10009–10009. doi:10.1200/jco.2017.35.15_suppl.10009

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다