Apalutamide Outperforms Enzalutamide in mCSPC Survival
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In an interview with Targeted Oncology, Neal Shore, MD, FACS, discussed the background, findings, and implications of a real-world study of enzalutamide and apalutamide in patients with metastatic castration-sensitive prostate cancer.
Neal Shore, MD, FACS
Findings from a real-world analysis of patients with metastatic castration-sensitive prostate cancer (mCSPC) revealed that treatment with apalutamide (Erleada) is associated with improved survival at 24 months compared with enzalutamide (Xtandi).
A higher proportion of patients in the apalutamide cohort survived by 24 months following treatment initiation, with survival rates of 85.4% for apalutamide vs 73.9% for enzalutamide. An unadjusted hazard ratio of 0.59 (95% CI, 0.39, 0.95; P =.030) indicates a significant difference in outcomes, underscoring the need for further studies that adjust for potential confounding variables to better inform clinical treatment decisions for patients with mCSPC.
The ROME study analyzed data from 234 patients treated with apalutamide. The mean age of patients was 73.2 years, 59.8% of patients were White, and 13.7% of patients were Black. Additionally, 527 patients were treated with enzalutamide. Among these patients, the mean age was 73.9 years, 55.2% of patients were White, and 13.1% were Black. The median time on treatment for the apalutamide group was 10.9 months, observed over a median period of 13.3 months. For the enzalutamide group, the median time on treatment was slightly longer at 11.1 months, with a median observation period of 14.8 months.
This retrospective longitudinal cohort study utilized clinical data from the Flatiron Metastatic Prostate Cancer Core Registry Electronic DataMart covering the period from January 1, 2013, to May 31, 2023.
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 background, findings, and implications of this study in the real-world setting.
Two prostate cancer cells in the final stage of cell division: ©PRB ARTS - stock.adobe.com
Targeted Oncology: Why is it important to compare these drugs in a real-world setting?
Shore: Sometimes, randomized controlled trials are hard to accomplish there. We always like to do those, especially prospectively. But given the fact that these are both approved and highly effective drugs, I think it is interesting from a clinician standpoint, whether you are in the community or academic, to see what our real-world experience is and what do the data and registry large sets tell us?
Can you provide an overview of the ROME study and what was evaluated in it?
This was a retrospective, longitudinal cohort of patients, largely coming from the Flatiron registry, which is an electronic dataset and patient charts interrogated from January 1, 2013, through May 31, 2023. Patients had to have had a chart confirm metastasis without any castration resistance findings. We had 2 cohorts based on the earliest initiation of either apalutamide or enzalutamide on or after the index date of December 2019. Patients had to have had greater 12 months of clinical data prior to the index and were followed from the index date until the earliest of 24 months post the index and the end of clinical activity or the end of data availability.
When we looked at important data metrics such as the date of death, their Social Security death index, and other confirmed sources, we took an analysis called an intention-to-treat approach. A Kaplan-Meier analysis used to describe the proportion of patients surviving 2 years, 24 months, postindex. We also used an unadjusted Cox proportional hazards model to describe any differences in survival rates between patients who are either initiated with apalutamide or enzalutamide.
There was a trend towards improved overall survival among those who received apalutamide. While it was not statistically significant, how do you interpret this finding?
We had over 230 patients in the apalutamide arm and a little over 520 patients in the enzalutamide arm. The demographics were nicely balanced between White and Black patients, with a mean age of about 73 in both groups. Approximately 13% of patients were non-White [Black] in both arms. We observed that the median time on treatment was about 11 months, with a median observation period of just over a year for the apalutamide arm. For the enzalutamide group, the median time on treatment was also about 11 months, with a median observation period of about 15 months. By 2 years, a higher proportion of patients in the apalutamide cohort survived compared [with] the enzalutamide cohort, with an unadjusted hazard ratio of 0.59. The survival rates were 85.4% for the apalutamide group vs 73.9% for the enzalutamide group. While this study reports unadjusted analyses, we believe it is important for future studies to assess potential confounding variables.
Were any of these findings particularly notable?
It is always something where people ask, “How do you pick one drug over another?” We know that, for patients, monotherapy [androgen deprivation therapy (ADT)] is no longer the standard of care. This was an attempt to see, in real-world terms, if we are seeing any differences between 2 strong [androgen receptor (AR)] pathway inhibitor drugs: apalutamide and enzalutamide. We demonstrated that, in this particular set of patients—largely community-based, about 75% in the community—these are the data revealed to us.
Are there any specific patient factors that would impact your choice on treatment?
We can look at these real-world efficacy data, but there are some nuanced differences regarding safety and tolerability issues, which are important for the shared decision-making process. These 2 AR pathway drugs have contraindications for patients with seizures, and there are always concerns about fatigue. Additionally, there may be cognitive effects and issues related to rash, as well as cardiovascular impacts such as hypertension and a very low risk of arrhythmia. These are some of the factors that our colleagues need to consider.
What are the considerations that might influence one's choice between each drug in real-world practice?
It is always a valuable opportunity in the community to have a shared decision-making moment, provided that accessibility is not an issue. This includes considerations such as starting with samples, costs, and reimbursement. When looking at the dosing regimens, both drugs can be taken once a day, with or without food, and they can be administered in either 4 pills or 2 capsules. It is important to consider the specific patient in front of you and what matters to them. You can certainly review the hazard ratios from the data, such as in ARCHES [NCT02677896] and TITAN [NCT02489318] studies, along with the different safety profiles, to help the patient make an informed decision, assuming they have the ability to choose either option.
What are the next steps for this research?
It is important to think about doing a prospective study. If we could do that, if someone wants to put the resources behind it, then there are other datasets as well and other registries, not just in the US, but outside the US that one can certainly interrogate retrospectively.
