Real-World Survival Outcomes in mCSPC: Comparison of Apalutamide and Abiraterone
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Neal Shore, MD, FACS, discussed a study on survival outcomes in metastatic castration-sensitive prostate cancer comparing apalutamide with abiraterone acetate.
Neal Shore, MD, FACS
A higher proportion of androgen receptor signaling inhibitor (ARSI)-naive patients with metastatic castration-sensitive prostate cancer (mCSPC) survived 24 months after initiating treatment with apalutamide (Erleada) vs those who began treatment with abiraterone acetate (Zytiga).
Specifically, 85.7% of patients in the apalutamide cohort were alive at 24 months, compared with 75.9% in the abiraterone acetate cohort, yielding an unadjusted hazard ratio of 0.60 (95% CI, 0.38-0.96; P =.033). The median time on treatment was 11.4 months for the apalutamide cohort and 10.8 months for the abiraterone acetate cohort.
Data were sourced from the Flatiron Metastatic Prostate Cancer Core Registry, covering January 1, 2013, to May 31, 2023. Patients with chart-confirmed metastasis who initiated treatment with apalutamide or abiraterone on or after September 17, 2019, were analyzed. Patients were followed for up to 24 months posttreatment initiation.
Overall, apalutamide may lead to better survival rates than abiraterone in patients with mCSPC. Further studies are needed to confirm these findings and explore potential confounding variables.
In an interview with Targeted OncologyTM, Neal Shore, MD, FACS, United States chief medical officer of surgery and oncology, GenesisCare USA, and director of the Carolina Urologic Research Center, discussed the findings of this study that highlighted the survival outcomes of patients with mCSPC treated with apalutamide vs those treated with abiraterone acetate.
3D rendered medically accurate illustration of prostate cancer: © SciePro - stock.adobe.com
Targeted Oncology: Can you provide an overview of the ROMA trial?
Shore: We have known since the approval of doublet or couplet therapy for our patients with mCSPC that 2 important studies using a combination of [androgen deprivation therapy (ADT)], abiraterone acetate, and prednisone—the LATITUDE trial [NCT01715285] and the STAMPEDE trial [NCT00268476]—have shown that doublet therapy works very well, certainly much better than monotherapy ADT. This was further supported by the CHAARTED [NCT00309985] and STAMPEDE studies for ADT and docetaxel. Additionally, the TITAN study [NCT02489318] demonstrated that ADT combined with apalutamide was superior to ADT alone.
The background for the ROMA study was to evaluate what a retrospective large registry dataset could reveal. Specifically, we utilized the Flatiron dataset, which is a highly regarded US dataset primarily composed of community oncology practices with some academic institutions. We looked at patients who were indexed, allowing us to follow them from their index date starting in mid-September 2019 for at least 2 years afterward, in addition to having 12 months of data before their index date. This study is helpful for understanding, in the real world, whether there are any differences between the doublet of ADT with apalutamide vs the doublet of ADT with abiraterone acetate.
What were the key findings from the study?
Demographically, the age was balanced at around 73 years. The proportion of White vs Black patients was also balanced, approximately 57% to 60% vs 14% to 17%. The time on treatment was comparable. However, when following these patients for 24 months from their index date, about 85% of the apalutamide cohort and about 76% of the abiraterone cohort were alive, resulting in an unadjusted hazard ratio of 0.60. Essentially, we observed that more treatment-naive patients with mCSPC survived by using apalutamide compared with abiraterone.
These are unadjusted comparisons, and we recognize that additional causal analyses, including comorbidities and other crossover therapies, are important for this analysis and could be confounding factors. It is valuable to report data from a real-world registry. There are nuanced differences in how these medications are taken, including fed state versus nonfed state, prednisone vs no prednisone, and different adverse events of interest such as fluid retention, glycemic issues, and rash.
Additionally, some of the lab monitoring is clearly different in terms of the frequency for obtaining potassium levels and liver function tests. Those are some of the differences. While this is a real-world, retrospective study, it raises the question of whether we can learn more from prospective direct comparator studies, which can be challenging to accomplish. This study provides another piece of evidence for clinicians to consider during the shared decision-making process with their patients.
Would you say this study confirms the previously observed survival advantages with apalutamide in this patient population?
I think it is corroborative to some earlier studies. There are some [individuals] who feel that pathway inhibitors potentially have greater efficacy than an androgen biosynthesis ligand binding inhibitor, so that has been debated. This particular study, with its limitations, seems to support that.
Does the observed efficacy and safety of these 2 agents differ among subgroups of patients with mCSPC?
Overall, there is room for further exploration, particularly for patients who may have more issues with drug tolerability. For instance, what happens if they are not tolerating the drugs well due to fluid retention or glycemic issues? Additionally, concerns about the frequency of lab monitoring or other issues related to prednisone use could impact the durability of therapy. I believe these factors are all important components of the shared decision-making discussion.
What are the most critical areas for further research in this space?
It always seems that the real gold standard would be a prospective, double-blind controlled trial as a direct comparator study for the different androgen receptor pathway drugs or AR-targeted agents. We have a lot of acronyms for these drugs, and we often find ourselves with what is referred to as an "embarrassment of riches," including abiraterone, apalutamide, enzalutamide [Xtandi], and darolutamide [Nubeqa]. It would be wonderful to conduct a large, fully blinded study to see how these drugs would perform in a prospective manner. However, such studies are not always easy to conduct and require a significant commitment and funding to perform successfully.
