The phase 3 NRG Oncology/RTOG (Radiation Therapy Oncology Group) 0521 trial aimed to evaluate if there was any benefit to adding docetaxel chemotherapy (CT) to standard treatment with long-term androgen suppression (AS) plus radiotherapy (RT) in men with prostate cancer considered to have high-risk disease without evidence of metastasis.1 Docetaxel had been routinely used in men with metastatic castration-sensitive prostate cancer with improvements in overall survival (OS), therefore, there was interest to study its impact in a different subgroup of men with prostate cancer.1
This initial study led by Rosenthal and colleagues found that docetaxel improved OS from 89% to 93% (hazard ratio (HR); 0.69; 90% CI, 0.49 to 0.97; one-sided P = .034). There was also a decrease in the 6-year rate of distant metastasis (DM) in the docetaxel group (9.1%) compared with the AS + RT-only group (14%; HR, 0.60; 95% CI, 0.37-0.99; two-sided P =.044). Finally, the docetaxel group had a higher 6-year disease-free survival (DFS) rate of 65% compared with 55% in AS + RT (HR, 0.76; 95% CI, 0.58-0.99; two-sided P =.043). This study had a median follow-up of 5.7 years. Recently, new longer-term data from the same study with a median follow-up among survivors of 10.4 years was published by Sandler and colleagues.2
The data reported in this abstract noted that of the 612 patients accrued, 563 were eligible for data analysis. Ten-year OS rates were higher in the docetaxel CT + AS + RT group (69%, 95% CI: 63% to 75%) compared to AS + RT alone (64%, 95% CI: 58% to 70%), although the findings were not statistically significant (HR = 0.89, 90% CI: 0.7-1.13, 1-sided p = 0.22). This led the authors to perform a Grambsch-Therneau test, which showed that there was evidence of non-proportional hazards (p =0.016). The authors subsequently re-evaluated OS using the restricted mean survival time (RMST) which showed a small statistical improvement in the OS of the CT + AS + RT group of 0.42 years (90% CI: 0.07-0.77, 2-sided p = 0.048).
Similarly, the cumulative incidence of distant metastasis (DM) was lower in the docetaxel CT + AS + CT group at 20% (95% CI, 15% to 25%) compared with the AS + RT only group at 22% (95% CI, 17% to 27%), although this again was not statistically significant (2-sided log-rank, P =.29). There was no statistical difference in the number of patient deaths between the 2 groups, and no new treatment-related grade 5 toxicities were reported.
Based on this updated long-term data, it appears that most of the benefit of adding docetaxel to AS + RT in men with high-risk prostate cancer is modest and observed earlier in the treatment course, as shown in the initial study.
The safety data included in this abstract was limited, but it does not appear that any new toxicities developed. The authors mentioned that a future pooled analysis may be conducted in order to expand the number of total patients that have received docetaxel in the same clinical setting.
Aside from this study, there have been several other studies evaluating docetaxel in a similar patient population including GETUG-12 (Groupe d’étude des Tumeurs Urogénitales), SPCG-12 (Scandinavian Prostate Cancer Group) and SPCG-13.1 Future studies can also aim to find new biomarkers that could help determine the best candidates for adding docetaxel to their regimen.
When evaluating these data, especially with the modest improvements shown, it is important to note the details of adding docetaxel to a patient’s regimen. For the patients receiving docetaxel, the protocol called for 6 cycles of docetaxel 75 mg/m2 intravenously (IV) over 1 hour every 21 days and prednisone 10 mg by mouth daily until 21 days after the last cycle of docetaxel. Depending on the patient, this could be a challenging regimen to follow in the real-world setting. Although docetaxel appeared to be relatively well tolerated in the initial study, the associated toxicities need to be thoroughly reviewed with the patient. It will be important to collect patient-reported outcomes from patients treated with docetaxel in order to further guide a treatment decision.
- Rosenthal SA, Hu C, Sartor O, et al. Effect of chemotherapy with docetaxel with androgen suppression and radiotherapy for localized high-risk prostate cancer: The randomized phase 3 NRG Oncology RTOG 0521 Trial. J Clin Oncol. 2019;37(14):1159-1168.
- Sandler HM, Karrison T, Sartor AO, et al. Adjuvant docetaxel for high-risk localized prostate cancer: Update of NRG Oncology/RTOG 0521. J Clin Oncol. 2020;38(6_suppl):333-333. Abstract 333.