ASCO 2023 RECAP Patient-reported Quality of Life and Survival Outcomes: CHAARTED Trial in Prostate Cancer
By: Daniel Sentana, MD, Beth Israel Deaconess Medical Center, Boston, Massachusetts | Posted on: 25 Oct 2023
Chemohormonal therapy, meaning androgen deprivation therapy (ADT) plus docetaxel (ADT+D), showed improved overall survival (OS) compared to ADT alone in men with metastatic hormone-sensitive prostate cancer (mHSPC) in the ECOG-ACRIN Cancer Research Group E3805 study (CHAARTED [ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer]).1 Docetaxel became standard of care for patients with high volume of disease, defined as either visceral metastases or ≥4 bone lesions with ≥1 beyond the vertebral bodies and pelvis, as longer follow-up revealed that the benefit was limited to this cohort.2 Additionally, the patient-reported outcomes collected throughout the study found that patients on ADT+D had significantly higher quality of life (QOL) at 12 months than those who only received ADT, even accounting for temporarily lower QOL at 3 months.3
Understanding the prognostic value of QOL is paramount to patients and providers alike, particularly in mHSPC where multiple treatment options have been shown to be beneficial but there is often ambiguity in deciding the right sequencing and timing.4,5 Based on these findings, we wanted to retrospectively evaluate the relationship between QOL and OS in men treated with ADT+D vs ADT alone. We chose baseline QOL and 3-month time point as we felt they likely reflected peak disease burden and treatment side effects, respectively. We focused on the Functional Assessment of Cancer Therapy–Prostate (FACT-P) out of the QOL instruments used in the trial, as it assesses the global QOL specifically for prostate cancer patients.6 The study population of CHAARTED has been previously described,1 but it is worth highlighting that most patients in this trial were younger men with good performance status, who had high risk and high volume of disease, and often had first presented with metastatic cancer.
In our main analysis, we tested the association between FACT-P total score and OS. We divided the FACT-P score range by quartiles, where higher scores indicate better QOL. On univariate analysis, there appeared to be a link with survival and higher scores in both baseline and 3-month time points. However, once the analysis adjusted for treatment arm, performance status, disease volume, Gleason score, and prior local therapy (all of which are independently prognostic variables), this relationship between QOL and OS was only sustained for 3-month scores, while perhaps there was a suggestive trend for baseline scores (Table 1).
Table 1. Association Between Functional Assessment of Cancer Therapy–Prostate Total Score (Quartile) and Overall Survival
|UVA n=790||MVAk n=705|
|Baseline FACT-P total score||N||HR (95% Cl)||P value||N||HR (95% Cl)||P value|
|[108, 123]||166||0.80 (0.62, 1.02)||.07||165||0.85 (0.67, 1.10)||.22|
|[123, 134]||176||0.70 (0.55, 0.90)||.005||176||0.94 (0.73, 1.21)||.61|
|[134, 156]||177||0.70 (0.55, 0.90)||.005||177||0.80 (0.62, 1.04)||.09|
|3-mo FACT-P total score|
|[105, 121]||160||0.89 (0.69, 1.15)||.39||160||0.9 (0.69, 1.17)||.42|
|[121, 133]||163||0.81 (0.63, 1.05)||.11||163||0.86 (0.66, 1.12)||.26|
|[133, 155]||158||0.71 (0.55, 0.93)||.011||158||0.76 (0.58, 1)||.05|
|Abbreviations: CI, confidence interval; FACT-P, Functional Assessment of Cancer Therapy–Prostate; HR, hazard ratio; MVA, multivariate analysis; UVA, univariate analysis.
Adjusted for treatment arm, performance status, disease volume, Gleason score, and prior local therapy.
Bold value indicates statistical significance.
Examining the survival at the extremes of QOL (the highest and lowest quartiles) at 3 months, we saw that ADT+D patients had no difference in survival between the patients with the highest and lowest QOL. On the other hand, patients who only received ADT had a very different survival probability between the patients with the highest and lowest QOL (see Figure). When we tested the association between treatment arm and 3-month QOL within the highest and lowest quartiles, we saw that patients with the highest QOL didn’t appear to derive a benefit from docetaxel. On the other hand, patients with the poorest QOL did seem to have better survival if they received docetaxel (Table 2).
Table 2. Association Between Treatment Arm and Overall Survival Within the Best and Worst 25% of 3-month Functional Assessment of Cancer Therapy–Prostate Scores
|Best 25% 3-mo FACT-P score||Worst 25% 3-mo FACT-P score|
|MVA (n=158)||MVA (n=165)|
|Treatment arm||N||HR (95% Cl)||P value||N||HR (95% Cl)||P value|
|ADT+D||73||1.11 (0.73, 1.67)||.63||87||0.69 (0.48, 0.99)||.047|
|Abbreviations: ADT, androgen deprivation therapy; CI, confidence interval; D, docetaxel; FACT-P, Functional Assessment of Cancer Therapy–Prostate; HR, hazard ratio; MVA, multivariate analysis. Bold value indicates statistical significance.|
To sum up, our exploratory analysis revealed an association between 3-month QOL assessed by FACT-P and OS in mHSPC patients. Moreover, the patients who had the poorest QOL, or the most symptomatic, had a survival benefit with ADT+D, independent of disease volume. Conversely, patients with the highest QOL, so the least symptomatic, did not appear to benefit from docetaxel even again independent of disease volume. Naturally, this is a retrospective analysis that the original study was not powered for, as its primary objective was median OS. That said, the dedicated collection of patient-reported outcomes during the trial did provide a sufficiently large data set to test the association between QOL and survival.
We think these findings are thought provoking since medical oncologists are trying to find out how patient-reported outcomes can supplement routine clinical care.7,8 Knowing a patient’s baseline QOL and at 3 months into chemohormonal treatment could help inform whether it makes sense for patients to continue with treatment or rather may not benefit from intensification. Since the field moves faster than we can study it, future trials should prospectively evaluate whether these findings can be replicated in the triplet era of mHSPC, where chemohormonal treatment is currently being used.
- Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373(8):737-746.
- Kyriakopoulos CE, Chen YH, Carducci MA, 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):1080-1087.
- Morgans AK, Chen YH, Sweeney CJ, et al. Quality of life during treatment with chemohormonal therapy: analysis of E3805 chemohormonal androgen ablation randomized trial in prostate cancer. J Clin Oncol. 2018;36(11):1088-1095.
- Achard V, Putora PM, Omlin A, Zilli T, Fischer S. Metastatic prostate cancer: treatment options. Oncology. 2022;100(1):48-59.
- Menges D, Yebyo HG, Sivec-Muniz S, et al. Treatments for metastatic hormone-sensitive prostate cancer: systematic review, network meta-analysis, and benefit-harm assessment. Eur Urol Oncol. 2022;5(6):605-616.
- Sentana Lledo D, Chu X, Jarrard DF, et al. Patient reported quality of life (QOL) and survival outcomes: analysis of ECOG-ACRIN E3805 chemohormonal androgen ablation randomized trial (CHAARTED) in prostate cancer (PCa). J Clin Oncol. 2023;41(16 Suppl):5014.
- Basch E, Schrag D, Henson S, et al. Effect of electronic symptom monitoring on patient-reported outcomes among patients with metastatic cancer: a randomized clinical trial. JAMA. 2022;327(24):2413-2422.
- Rocque GB, Dent DN, Ingram SA, et al. Adaptation of remote symptom monitoring using electronic patient-reported outcomes for implementation in real-world settings. JCO Oncol Pract. 2022;18(12):e1943-e1952.