A. Oliver Sartor, MD

During a Targeted Oncology Case-Based Roundtable event, A. Oliver Sartor, MD, C. E. & Bernadine Laborde professor of Cancer Research, medical director, Tulane Cancer Center, and assistant dean for Oncology at Tulane University School of Medical, discussed the results of cabazitaxel (Jevtana) as a later-line treatment for patients with metastatic castration-resistant prostate cancer (CRPC).

: What are the initial options for treatment for this patient population?

: The NCCN [National Comprehensive Cancer Network] guidelines give you plenty of options. You have category 1, but it is based on older data prior to the use of the abiraterone [Zytiga] and enzalutamide.

 I cannot imagine using mitoxantrone in this circumstance, to be honest. The fine-particle abiraterone is just a variation on abiraterone, and other secondary hormones I wouldn’t utilize.

One of the tactics that we use for cost-effectiveness sometimes is using the abiraterone with food instead of fasting and using a little lower dose. Sometimes we encounter co-pay problems; the drug costs are high. Using the abiraterone with food is something that we do on occasion.

Please describe the rationale and design for the trial that looked at the use of cabazitaxel.

This is the [phase 4] CARD trial [NCT02485691] where patients had metastatic CRPC [castration-resistant prostate cancer]. Patients progressed after less than 12 months on a prior alternative novel hormone—in this case, it’s one of the newer androgen receptor [AR]–targeted agents, such as abiraterone and enzalutamide. They enrolled 255 patients, randomized 1:1 between cabazitaxel and either abiraterone or enzalutamide. The primary end points were radiographic progression- free survival [rPFS], with key secondary end points of overall survival [OS], progression-free survival [PFS], PSA, etc.

[This was] not a young population, [aged] about 70 to 71 years, which I think is typical from our practice. The vast majority had an ECOG performance status 0 to 1 and visceral metastases [were] relatively well balanced in both groups. The type of progression at the time of study entry was often [when the patient was experiencing] pain, and that’s interesting because I think we’ve gotten accustomed to looking at a lot of these studies where it’s PSA-only progression, but a lot of these patients had pain progression.

Most patients also had Gleason score 8 to 10 and a substantial number, but certainly not the majority, had M1 disease at diagnosis. Patients received docetaxel [Taxotere] or abiraterone only in a minority for metastatic hormone-sensitive or castration-sensitive cancer. The prior alternative AR-targeted agent was abiraterone or enzalutamide, and this was relatively well balanced. They received it either before or after docetaxel in an equal fashion. The median duration of the alternative AR-targeted agent, the abiraterone and enzalutamide that proceeded the randomization, was about 7.6 to 8 months.

What were the efficacy outcomes of this study?

The primary end point of rPFS had a very strong hazard ratio of 0.54 [95% CI, 0.40-0.73; P < .0001]. Median rPFS was 8 months versus 3.7 months in [the cabazitaxel and hormone therapy arms, respectively].3 This was not a particularly good performance from the hormones therapy with a P value less than .001, so quite strong data [for cabazitaxel]. All the subgroups seemed to benefit from the cabazitaxel, and there was no subset identified where the hormonal agent was better.

The trial was not powered for OS, but it was positive anyway. The hazard ratio was 0.64 [95% CI, 0.46-0.89; 

 = .0078] and it had a relatively modest median of 13.6 months to 11 months [in the cabazitaxel and abiraterone or enzalutamide arms, respectively]. For PFS, which would include not just the rPFS but the symptomatic progression, there was benefit. The hazard ratio for PFS was 0.52 [95% CI, 0.40-0.68; 

 < .0001], so again, PSA responses were also statistically significant [

 = .0002], objective tumor response was statistically significant [

 = .004], and pain response was also statistically significant [

 < .0001], with everything favoring the cabazitaxel arm. There was also a strong trend in time to SSE [symptomatic skeletal events] even with the median SSE not reached [

What were the adverse events (AEs) associated with these data?

AEs are going to happen, but serious AEs were balanced, 38.9% to 38.7% [in the cabazitaxel and abiraterone or enzalutamide arms, respectively].4 The grade 3 or higher AEs [were more in the cabazitaxel arm], 56.3% to 52.4%. AEs leading to discontinuation were 19.8% [in the cabazitaxel arm, which was] acceptable. AEs leading to death, however, were higher in the abiraterone or enzalutamide arm.

[The probability of deterioration at 3 months] performed well and adjusted mean changes from baseline on the pain scales, well-being scales, and a pain benefit with a P value of less than .001.5 Clearly, a better pain-related subscale on the quality-of-life scores.

How do these data affect your practice and treatment decisions?

I was one of the coinvestigators on [a trial] published way back in 2010 with cabazitaxel. I’ve had a fair amount of experience in terms of using it. It’s a dose-related phenomenon; I tend to use the 20 mg/m

 to get going, but it’s an effective agent. I don’t think there’s any doubt about cabazitaxel being able to be active in the docetaxel-progressing patients. This setting was where docetaxel was discontinued because of toxicity and clearly cabazitaxel is available there. So these are good data.

1. NCCN. Clinical Practice Guidelines in Oncology. Prostate cancer, version 2.2020. Accessed May 3, 2021. https://bit.ly/3tgVTBo

2. de Wit R, de Bono J, Sternberg CN, et al; CARD Investigators. Cabazitaxel versus abiraterone or enzalutamide in metastatic prostate cancer. 

. 2019;381(26):2506-2518. doi:10.1056/NEJMoa1911206

3. Fizazi K, et al. Pain response and health-related quality of life (HRQL) analysis in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving cabazitaxel (CBZ) versus abiraterone or enzalutamide in the CARD study. 

. 2020;38(suppl 6):16. doi:10.1200/JCO.2020.38.6_suppl.16

4. de Wit R, Kramer G, Eymard JC, et al. CARD: randomized, open-label study of cabazitaxel (CBZ) vs abiraterone (ABI) or enzalutamide (ENZ) in metastatic castration-resistant prostate cancer (mCRPC). 

. 2019;30(suppl 5):v851- v934. doi:10.1093/annonc/mdz394

5. Fizazi K, Kramer G, Eymard JC, et al. Quality of life in patients with metastatic prostate cancer following treatment with cabazitaxel versus abiraterone or enzalutamide (CARD): an analysis of a randomised, multicentre, open-label, phase 4 study. 

. 2020;21(11):1513-1525. doi:10.1016/S1470-2045(20)30449-6

Articles

During a Targeted Oncology Case-Based Roundtable event, A. Oliver Sartor, MD, discussed the results of cabazitaxel as a later-line treatment for patients with metastatic castration-resistant prostate cancer.

Cabazitaxel Advances Later-Line Treatment in Metastatic CRPC Setting

A. Oliver Sartor, MD, professor of Medicine, medical director of Tulane Cancer Center, and C. E. and Bernadine Laborde Professor of Cancer Research at Tulane University, discusses the design for an observational study (NCT02141438) of disease characteristics and outcome of patients with metastatic castration-resistant prostate cancer (mCRPC) who received 177Lu-PSMA after receiving radium-223.

According to the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program, the outcome was that grade 3/4 hematologic adverse events after treatment with radium-223 were low and treatment with subsequent 177Lu-PSMA seems feasible.

Sartor says that there is a fair group of investigators that have been involved with looking at longer-term follow-up of the use of radium-223 in these patients. There is an extensive database that investigators can use to understand what the ultimate outcomes may be for patients with mCRPC who were treated in selected center involved with a prospective registry.

In addition to outcomes such as secondary cancers and survival, the investigators also collected data for this study in regard to subsequent therapies, according to Sartor. They don’t understand yet if the subsequent therapies were effective or not, but they did look at whether they were used and for how long to get durations of survival. He says the substrate for the study was patients who were on radium-223 at selected practices participating in a prospective registry and were also reporting on subsequent use of 177Lu-PSMA in patients.

<< View more resources and information regarding prostate cancer

Videos

A. Oliver Sartor, MD, discusses the design for an observational study of disease characteristics and outcome of patients with metastatic castration-resistant prostate cancer who received 177Lu-PSMA after receiving radium-223. 

Exploring the Design for Longer Follow-Up of Radium-223 in mCRPC

A. Oliver Sartor, MD, professor of medicine, medical director, Tulane Cancer Center, C. E. and Bernadine Laborde Professor of Cancer Research, discusses the current treatment options for patients with nonmetastatic castration-resistant prostate cancer (CRPC) and what physicians should consider when selecting treatment for their patients.

Three agents are approved for the treatment of nonmetastatic CRPC, which include apalutamide (Erleada), enzalutamide (Xtandi), and darolutamide (Nubeqa). All 3 drugs were tested in clinical trials, which resulted in positive findings that the FDA based their approvals on, says Sartor.

Between these 3 agents, there are some differences in terms of toxicities. However, there are no head-to-head trials to compare these. Sartor recommends considering the cost of the therapy, as well as potential implications for subsequent therapies when selecting 1 of these 3 agents to treat patients with nonmetastatic CRPC. He says we don&rsquo;t know how patients who have been previously treated with these agents should be treated, so further data and analysis are necessary.

A. Oliver Sartor, MD, discusses the current treatment options for patients with nonmetastatic castration-resistant prostate cancer (CRPC) and what physicians should consider when selecting treatment for their patients.

Exploring FDA-Approved Therapies for Nonmetastatic Castration-Resistant Prostate Cancer

A. Oliver Sartor, MD, professor of medicine, medical director, Tulane Cancer Center, C. E. and Bernadine Laborde Professor of Cancer Research, discusses a discrepancy found between conventional imaging and PSMA PET/CT scanning for prostate cancer.&nbsp;

Following FDA approvals for apalutamide (Erleada), enzalutamide (Xtandi), and darolutamide (Nubeqa), further investigation was done to understand what percentage of these patients&nbsp;who received these agents&nbsp;may have PSMA PET/CT scan positivity, says Sartor.&nbsp;

Utilizing patient characteristics from a trial of enzalutamide, this analysis showed that 98% of patients were PET positive, explains Sartor. Moreover, 55%&nbsp;of patients&nbsp;were classified&nbsp;as having metastatic disease,&nbsp;despite being deemed nonmetastatic by conventional imaging.&nbsp;

These findings do not change the metastasis-free survival benefit demonstrated with apalutamide, enzalutamide, and darolutamide, says Sartor. The drugs were investigated using&nbsp;conventional imaging and showed a prostate-specific antigen doubling time of 10 months.

A. Oliver Sartor, MD, discusses a discrepancy found between conventional imaging and PSMA PET/CT scanning for prostate cancer.&nbsp;

Conventional Imaging Versus PSMA PET/CT Scanning in Prostate Cancer

A. Oliver Sartor, MD, Director of the Tulane Cancer Center, discusses the recent progress for the treatment of prostate cancer.

At the 2013 American Society of Clinical Oncology (ASCO) Meeting, Sartor says, there was not much clinical progress in prostate cancer presented, as there was no new positive phase III data.

There was, however, progress on the molecular front. Molecular scientists are getting better at analyzing RNAs, DNAs, and mutations and it is now possible to genomically analyze cancer cells at a single cell level from the bloodstream. This finding is truly remarkable, Sartor says.

In a recent study, it was demonstrated that one cancer cell in a patient and another are not necessarily the same: Heterogeneity extends down to the cellular level. There is still a lot to learn, Sartor insists, as the approach to developing targeted therapies is more difficult than previously thought.

Radium-223 is unique in this regard, in that it can overcome heterogeneity and kill all mutations.

There has been recent progress on the molecular front for the treatment of prostate cancer

It is now possible to genomically analyze single cancer cells

Cancer heterogeneity extends to the cellular level

A. Oliver Sartor, MD | Authors

Articles

Cabazitaxel Advances Later-Line Treatment in Metastatic CRPC Setting

Exploring the Design for Longer Follow-Up of Radium-223 in mCRPC

Exploring FDA-Approved Therapies for Nonmetastatic Castration-Resistant Prostate Cancer

Conventional Imaging Versus PSMA PET/CT Scanning in Prostate Cancer

Recent Progress on the Molecular Front for the Treatment of Prostate Cancer