ASCO Adds New Combos for Metastatic Noncastrate Prostate Cancer

Oncology Live®, Vol. 19/No. 15, Volume 19, Issue 15

Use of androgen deprivation therapy in combination with docetaxel or abiraterone in newly diagnosed cases of metastatic noncastrate prostate cancer is recommended in recently updated ASCO guidelines.

Use of androgen deprivation therapy (ADT) in combination with docetaxel (Taxotere) or abiraterone (Zytiga) in newly diagnosed cases of metastatic noncastrate prostate cancer (mNCPC) is recommended in recently updated American Society of Clinical Oncology (ASCO) guidelines. Historically, mNCPC has been treated with ADT alone until progression; ASCO noted a survival benefit from adding docetaxel or abiraterone, based on a review of several trials.1

However, the new guidelines indicate that patients with mNCPC should not receive docetaxel or abiraterone either in combination or in a series because no data from randomized clinical trials compare these 2 agents directly when added to ADT, and it is not known if one regimen offers a superior survival benefit.

An ASCO expert panel looked at GETUG-AFU 15, STAMPEDE, and CHAARTED, which examined overall survival (OS) from adding docetaxel to ADT. STAMPEDE and CHAARTED favored docetaxel, and GETUG-AFU 15 was negative for additional benefit.

In CHAARTED, after a median follow-up of 28.9 months, OS was 13.6 months longer with ADT plus docetaxel versus ADT alone: 57.6 versus 44.0 months (HR, 0.61; 95% CI, 0.47-0.80; P <.001).2 STAMPEDE demonstrated a median OS of 81 months with docetaxel plus ADT versus 71 months with ADT alone (HR, 0.78; 95% CI, 0.66-0.93; i = .006).3

At a median follow-up of 83.9 months, GETUG-15 did not demonstrate a statistically significant difference in OS, but the results trended in favor of ADT plus docetaxel. The median OS was 48.6 months with ADT alone versus 62.1 months with ADT plus docetaxel (HR, 0.88; 95% CI, 0.68-1.14; P = .3).4

Table. Treatment Recommendations for De Novo Noncastrate Disease

The new guidelines strongly recommend that patients with mNCPC and high-volume disease who are candidates for treatment with chemotherapy be offered docetaxel in addition to ADT. The definition of high-volume disease in this patient population is based on the CHAARTED trial, which defined highvolume as the presence of any visceral disease or ≥4 bone metastases, with 1 or more outside the spine or pelvis.2 For patients with low-volume disease (according to CHAARTED) who are candidates for chemotherapy, the guidelines moderately recommend offering docetaxel (Table).The dosage of docetaxel alone or with prednisone is now listed as 6 doses at 75 mg/m2 administered every 3 weeks under a strong recommendation, based on both CHAARTED and STAMPEDE.1

LATITUDE and STAMPEDE each found OS improvement from adding abiraterone (with prednisone or prednisolone) to ADT. Results from LATITUDE showed a 38% reduction in the risk of death, with a median OS of 34.7 months in the ADT arm. Median survival was not reached in the combination arm (HR, 0.62; 95% CI, 0.51-0.76; P <.001).

The median radiographic progression-free survival with ADT plus abiraterone was 33.0 months versus 14.8 months for ADT alone, representing a 53% reduction in the risk of progression or death (HR, 0.47; 95% CI, 0.39-0.55; P <.001). The OS rate at 3 years was 66% in the abiraterone group versus 49% with ADT alone.5 Based on these results, in February 2018, the FDA approved abiraterone with prednisone for patients with metastatic, high-risk, castration-sensitive prostate cancer.6

Based on the LATITUDE study, it was strongly recommended that patients with high-risk de novo mNCPC be offered abiraterone and prednisone with ADT. High-risk disease is based on the LATITUDE criteria and includes a Gleason score ≥8, at least 3 bone lesions, and the presence of measurable visceral metastasis.5

Results of STAMPEDE showed a reduced risk of death of 37% for the overall study population (HR, 0.63; 95% CI, 0.52-0.76; P = .001) and 39% in the population with M1 disease (HR, 0.61; 95% CI, 0.49- 0.75; P <.05). The 3-year OS rate was 83% in the abiraterone group versus 76% in the ADT group.7 Based on STAMPEDE, it is moderately recommended that patients with lower-risk de novo mNCPC be offered abiraterone in combination with ADT.

The guidelines note that without randomized data comparing docetaxel with aberaterone, variables such as comorbidities, toxicity, quality of life, drug availability, and cost will need to be considered when choosing either treatment for a patient.

References

  1. Morris MJ, Rumble RB, Basch E, et al. Optimizing anticancer therapy in metastatic non-castrate prostate cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2018;36(15):1521-1539. doi: 10.1200/JCO.2018.78.0619.
  2. 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. doi: 10.1056/NEJMoa1503747.
  3. James ND, Sydes MR, Clarke NW, et al; STAMPEDE investigators. 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.
  4. Gravis G, Boher JM, Joly F, et al. Androgen deprivation therapy (ADT) plus docetaxel versus ADT alone in metastatic non castrate prostate cancer: impact of metastatic burden and long-term survival analysis of the randomized phase 3 GETUG-AFU15 trial. Eur Urol. 2016;70(2):256-262. doi: 10.1016/j.eururo.2015.11.005.
  5. Fizazi K, Tran N, Fein L, et al; LATITUDE investigators. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017;377(4):352-360. doi: 10.1056/NEJMoa1704174.
  6. Zytiga® (abiraterone acetate) plus prednisone approved for treatment of earlier form of metastatic prostate cancer [press release]. Horsham, PA: Janssen Pharmaceutical Companies; February 8, 2018. janssen. com/zytiga-abiraterone-acetate-plus-prednisone-approved-treatment- earlier-form-metastatic-prostate. Accessed June 28, 2018.
  7. James ND, DeBono JS, Spears MR, et al. Adding abiraterone for men with high-risk prostate cancer (PCa) starting long-term androgen deprivation therapy (ADT): survival results from STAMPEDE (NCT00268476). J Clin Oncol. 2017;35 (suppl; abstr LBA5003). doi: 10.1200/JCO.2017.35.18_suppl.LBA5003.