ASCO Denver 2024: Dr Graham Discusses Quality of Life in Prostate Cancer from the PSMAfore and EMBARK Trials
Presented by:
Laura S. Graham, MD, University of Colorado Cancer Center
Meeting:
2024 ASCO Direct™ Denver
The Bottom Line
Quality of life (QoL) is an important consideration for men receiving therapy for advanced prostate cancer, particularly as their treatment can be continued over many years. Results from two recent trials examined QoL outcomes for prostate cancer patients receiving two different kinds of therapy for their disease. For patients with advanced, castration resistant disease, QoL was prolonged with treatment, while for patients with hormone sensitive disease localized to the prostate, QoL did not deteriorate with cessation of therapy following a successful course of treatment for a biochemical recurrence (increasing PSA only).
Background
Men undergoing treatment for prostate cancer can experience both cancer-related symptoms, as well as significant side effects of treatment, including urinary and sexual dysfunction, that can cause significant impediment to their health-related quality of life (HRQoL). This is especially important to consider in relation to individual patient preferences, as often treatments can continue over several years. In some cases, treatment is given in the absence of any overtly detectable radiologic recurrence of their disease, for example, in the case of a rising prostate-specific antigen (PSA) level, which is generally regarded as an indication of disease progression in prostate cancer (often referred to as a “biochemical or PSA recurrence”).
PSMAfore
The PSMAfore Trial examined outcomes for patients with advanced, metastatic, castration-resistant prostate cancer (mCRPC) who underwent treatment with lutetium (Lu177-PSMA-617), a type of radioactive therapy for men with prostate-specific membrane antigen (PSMA)-positive mCRPC. Patients in the trial had confirmed mCRPC with at least 1 or more PSMA positive metastatic lesions, had not received a taxane-type chemotherapy (e.g., docetaxel) for their disease (“taxane-naïve”), had to have received prior treatment with at least 1 androgen receptor pathway inhibitor (ARPI) such as abiraterone or enzalutamide, and had to be eligible for a change in their ARPI. Patients in the trial received treatment with either lutetium, or a change in their ARPI, and if they had progression on ARPI, a crossover to lutetium was allowed. Most patients in the trial had bone metastases, and the median PSA level was about 15. Previously reported results from PSMAfore had indicated a significant benefit of lutetium over ARPI change, with a median radiographic progression free survival of 12.02 versus 5.59 months in the respective groups (P<0.0001). A significant benefit of lutetium over ARPI change in overall survival has not yet been observed, but the high level of crossover that was allowed in the trial, as described above, has been attributed to this result.
Quality of Life in PSMAfore
Results from PSMAfore on HRQoL reported at this year’s American Society for Clinical Oncology (ASCO) Meeting showed that there was a significantly longer time-to-worsening of HRQoL for patients receiving lutetium, as compared to the ARPI change. Time-to-worsening of other prostate specific HRQoL measures, including physical, functional, and emotional well-being as well as pain intensity, were also significantly improved with lutetium as compared to the ARPI change group. While these results are encouraging, Dr Graham also noted that at present the treatment is not yet approved in the United States for patients with mCRPC that is taxane-naïve. She further noted that HRQoL measures do not necessarily take into account all adverse events of treatment, and that patients on lutetium can experience significant side effects such as anemia, fatigue, and dry mouth.
EMBARK
Patients in the EMBARK trial had non-metastatic hormone sensitive prostate cancer (nmHSPC), with a biochemical recurrence (BCR) of their prostate cancer (i.e., a rising PSA with no radiographic evidence of recurrence) and also had high risk features, as defined in Box 1. Patients in the trial received treatment with enzalutamide (ENZ), an androgen receptor antagonist, either alone (monotherapy) or in combination with leuprolide, a gonadotropin releasing hormone (GnRH) analog type drug, or leuprolide monotherapy. Previously reported results had shown significant improvement in metastasis-free survival with the combination versus leuprolide alone in high risk, BCR, nmHSPC, and the combination therapy is now approved for use in this setting. Dr Graham noted an important aspect of the trial design, in that, regardless of treatment assignment, if by 37 weeks of treatment PSA had dropped to < 0.2 ng/ml, treatment was suspended, and was only reinstated if PSA rose to > 2.0 ng/ml (with a prior radical prostatectomy) or > 5.0 ng/ml (without a prior radical prostatectomy).
Box 1. High Risk Features for Patients with Non-Metastatic, Hormone Sensitive Prostate Cancer Having a Biochemical Recurrence After Local Therapy, As Defined in the EMBARK Trial
PSA > 1 ng/ml after radical prostatectomy
PSA > 2 ng/ml above the lowest level, following radiotherapy
PSA Doubling Time (PSADT) of < 9 months
Testosterone Level > 150 ng/ml
Quality of Life in EMBARK
Results from EMBARK reported at this year’s ASCO showed that, overall, there were no major changes or deterioration in QoL measures for patients following cessation of treatment once their BCR had been successfully treated. Dr Graham noted, however, that patients in EMBARK had asymptomatic BCR only, and did not have metastatic disease (for example, a painful bone lesion), therefore, patients would not be expected to have any significant pain or impairment of QoL to begin with; as such, it is difficult to draw any major conclusions about the impact of stopping the treatment on QoL, or a lack thereof. She further noted that the QoL measures used in the study might be more focused on prostate cancer related symptoms, and may not fully capture the impact and side effects of the treatment itself, which could also have an adverse impact on QoL for patients receiving long term therapy.
“We’re really walking this balance, especially in biochemical recurrence, of treatment before you get deterioration in cancer related symptoms, but also recognizing that people are going to be on therapy for a long time, so trying to give people some treatment breaks...”
Speaker Disclosure Information: Dr Graham reported the following disclosures for this presentation: Research funding to institution: SeaGen, Johnson & Johnson, Merck.