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.
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Data availability
We obtained the data from CHAARTED through the National Clinical Trials Network (NCT00309985-D3 and NCT00309985-D4). Data were originally collected from clinical trial NCT00309985. The data are publicly available through the NCTN.
References
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7–34.
National Cancer Institute. Cancer Stat Facts: Prostate Cancer. National Cancer Institute Surveillance, Epidemiology, and End Results Program. Published n.d. Accessed 30 April 2020. https://seer.cancer.gov/statfacts/html/prost.html
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. https://doi.org/10.1002/cncr.32630
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;387:1163–77.
Sweeney CJ, Chen Y-H, Carducci M, Liu G, Jarrard DF, Eisenberger M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373:737–46.
Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017;377:352–60.
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. N Engl J Med. 2017;377:338–51.
Chi KN, Agarwal N, Bjartell A, Chung BH, Gomes AJP, de S, et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019;381:13–24.
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. 2019;37:2974–86.
Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, et al. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019;381:121–31.
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. 2019;37:2961–7.
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;20:494–502.
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 Suppl 15:e23020–e23020.
Hurria A, Gupta S, Zauderer M, Zuckerman EL, Cohen HJ, Muss H, et al. Developing a cancer-specific geriatric assessment. Cancer. 2005;104:1998–2005.
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;36:2326–47.
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;6:1.
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;34:2366–71.
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:JCO.2017.75.365. https://doi.org/10.1200/jco.2017.75.3657
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:e12392.
Tsao PA, Caram MEV. Factors to guide treatment selection for hormone-sensitive metastatic prostate cancer. Cancer J. 2020;26:76–82.
Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N. Engl J Med. 2004;351:1502–12.
Scott JM, Stene G, Edvardsen E, Jones LW Performance status in cancer: not broken, but time for an upgrade? J Clin Oncol. Published online 2020:JCO2000721. https://doi.org/10.1200/jco.20.00721
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. https://doi.org/10.1002/cncr.30269
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 Suppl 15:10009. https://doi.org/10.1200/jco.2017.35.15_suppl.10009
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NIH T32 CA092203 (DEL).
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We made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data. All were involved in drafting the article or revising it critically for important intellectual content. All provided final approval of the manuscript and agree to be accountable for all aspects of the work.
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RJL reports consulting role for Bayer, Janssen, Astellas, and Dendreon. JAG reports research funding from Gaido Health/BCG Digital Ventures, NCCN/AstraZeneca (Inst); royalties from Springer (Humana Press); consulting role for Concerto HealthAI. JST reports research funding from Astra Zeneca and Pfizer. CJS reports consulting role for Sanofi, Janssen, Astellas Pharma, Bayer, Genentech, AstraZeneca, Pfizer, Lilly; research funding from Janssen Biotech (Inst), Astellas Pharma (Inst), Sanofi (Inst), Bayer (Inst), Sotio (Inst), Dendreon (Inst); patents/royalties from Pathenolide (Indiana University), dimethylaminoparthenolide (Leuchemix), Exelixis: Abiraterone plus cabozantinib combination; stock ownership in Leuchemix. No other conflicts of interest were identified.
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Lage, D.E., Michaelson, M.D., Lee, R.J. et al. Outcomes of older men receiving docetaxel for metastatic hormone-sensitive prostate cancer. Prostate Cancer Prostatic Dis 24, 1181–1188 (2021). https://doi.org/10.1038/s41391-021-00389-2
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DOI: https://doi.org/10.1038/s41391-021-00389-2
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