Dr. Rathkopf began with a discussion of the evolving therapeutic landscape for metastatic prostate cancer in 2020. She highlighted the multiple options at diagnosis, trials moving systemic therapy to earlier disease settings, and radiotherapy moving into later disease settings as complicating factors.
This complicated therapeutic landscape raises significant questions in selecting therapy for men with mHSPC. Should we consider molecular status when choosing between chemotherapy and androgen receptor (AR) targeted therapies? How do we integrate radiation in this setting (to the primary and/or oligometastatic disease)? How does prior therapy and/or presentation (de novo versus metachronous, high versus low volume disease) affect outcomes? The two abstracts that Dr. Rathkopf discussed addressed drug selection for the treatment of patients with mHSPC.
Dr. Neeraj Agarwal presented data on time to PFS2 in patients from TITAN with mCSPC by first subsequent therapy. PFS2 favored ADT plus apalutamide over ADT plus placebo in men who received either hormone therapy or taxane chemotherapy as next treatment. Dr. Rathkopf noted that only approximately 20% of patients in both subsequent therapy arms met criteria for PFS2 given the short follow-up. This analysis therefore is limited to the patients with poor responses to both first- and second-line therapy and may not be representative of the overall study population. Further follow-up is therefore needed to determine PFS2 by first subsequent therapy in the broader patient population with mCSPC treated with apalutamide.
Dr. Anis Hamid presented data on PAM50-Decipher genomic expression-based biomarkers for predicting docetaxel benefit in men with newly diagnosed mHSPC. In summary, patients with Basal subtype had significantly better overall survival (OS) when treated with ADT alone (47.1 months) than those with Luminal B subtype (29.8 months). In contrast, only patients with Luminal B subtype benefited from the addition of docetaxel to ADT (OS = 52.1 months). Docetaxel had no OS benefit (48.2 months) in patients with Basal subtype.
Dr. Rathkopf commented that although Luminal B subtype is associated with a good response to ADT in prostate cancer cell line models, it is also associated with a relatively poor prognosis and high proliferation rate; thus, it may be that the Luminal B response to ADT was good, but not good enough given the underlying aggressive biology of this subtype. The addition of docetaxel to ADT resulted in similar OS between patients with Luminal B and Basal subtypes. This suggests that patients with Luminal B may benefit more from docetaxel than those with Basal subtypes. Dr. Rathkopf cautioned that further validation is needed before we move this into clinical practice, but highlighted that exploration of basal-luminal clinical outcomes and validation of response to treatment in mHSPC is ongoing.
Presented by: Dana Rathkopf, MD, Medical Oncologist at Memorial Sloan Kettering Cancer Center
Written by: Jacob Berchuck, MD, Medical Oncology Fellow at the Dana-Farber Cancer Institute (Twitter: @jberchuck) at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California