ASCO GU 2020: Luminal B Subtype as a Predictive Biomarker of Docetaxel Benefit for Newly Diagnosed Metastatic Hormone Sensitive Prostate Cancer: A Correlative Study of E3805 CHAARTED

San Francisco, CA (UroToday.com) The phase III CHAARTED study evaluated docetaxel for treating metastatic hormone-sensitive prostate cancer.1 In all, 790 patients were randomly assigned to receive androgen-deprivation therapy (ADT) plus >6 docetaxel cycles (75 mg/m2), or ADT alone.



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After a median follow up of 53.7 months, median overall survival (OS) was 57.6 months for chemohormonal therapy vs. 47.2 months for ADT alone. Patients were classified as having high-volume or low-volume disease based on the presence of visceral metastases or ≥4 bone metastases, including >1 metastasis outside the vertebral column and pelvis. For patients with high-volume disease, median OS was 51.2 months with chemohormonal therapy vs. 34.4 months with ADT alone. No OS benefit was observed for patients with low-volume disease.

It is unknown if there other predictive factors might help guide patient selection. This study provides molecular subtyping analyses by using the PAM50 classifier to assess tumor luminal and basal status. Initially used to molecularly categorize breast cancers, PAM50 has been shown to predict ADT response in prostate cancer.2 In a study of 1,567 retrospectively collected and 2,215 prospectively collected tumor specimens, the PAM50 classifier consistently subtyped prostate tumor specimens as luminal A, luminal B, or basal. Post-operative ADT demonstrated greater antitumor activity in luminal B vs. non-luminal B tumors.

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The current study evaluates whether these same molecular subgroups predict docetaxel response in patients with metastatic hormone-sensitive prostate cancer.

Summary

Gene expression profiling data were completed for 160 patients. Most tumors were classified as luminal B (50%) or basal (48%), with only 2% classified as luminal A. The percentage of patients with luminal B or basal tumors did not significantly vary based on disease volume.


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Among patients with luminal B subtype prostate cancer, those who received docetaxel had a much longer OS and time to onset of castration resistance compared with those who did not. 


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Among patients with basal subtype prostate cancer, docetaxel did not significantly affect OS, but its use did prolong time to castration resistance.


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Conclusions

These data suggest that docetaxel may not benefit all patients in the metastatic hormone-sensitive setting. If additional data validate these findings, clinicians might consider submitting tumor specimens for molecular subtyping to help select patients for chemotherapy. As there are numerous treatments now available for metastatic hormone-sensitive prostate cancer, it would be interesting to study whether this relationship holds true only for taxane-based chemotherapy or is prognostic or predictive for outcomes with other treatments.

Presented by: Anis Hamid, MBBS, Research Fellow, Dana-Farber Cancer Institute

Written by: Jason Zhu, MD. Medical Oncologist, Division of Genitourinary Cancers, Levine Cancer Institute Twitter: @TheRealJasonZhu at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California

References:

  1. Kyriakopoulos CE, Chen Y-H, Carducci MA, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial. Journal of Clinical Oncology 2018;36:1080.
  2. Zhao SG, Chang SL, Erho N, et al. Associations of luminal and basal subtyping of prostate cancer with prognosis and response to androgen deprivation therapy. JAMA oncology 2017;3:1663-72.
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