Metastatic CRPC: Selecting Patients for Cabazitaxel or Radiotherapy

Comprehensive insight on factors that may influence the selection of cabazitaxel or radiotherapy for patients with metastatic castration-resistant prostate cancer.

Tanya Dorff, MD
: With the recent approval of lutetium-177-PSMA-617 [prostate-specific membrane antigen or PSMA], I feel a similar scenario is playing out because of the access issues. But—

Elisabeth Heath, MD, FACP: Yes.

Tanya Dorff, MD: If we can step back from the access issues and take those out of the equation, we do have this other option. In some patients, we might use cabazitaxel, or we could use lutetium PSMA. How are you making that decision?

Elisabeth Heath, MD, FACP: We can go over the studies, but the big driver here is, patients. We’ve been talking about lutetium-177 and felt as if, “We’re going to get it; it’s going to happen. You can fly to Europe and do whatever is needed and then come back.” In the discussions that patients have had among themselves...there’s a push for wanting to get the new drug. The therapy trial tried to ask the question “Is it lutetium or [cabazitaxel]? What’s the final verdict?” But I don’t think we have the final verdict yet. We want to know which has the better overall survival rate and that [information is] not ready yet. You may be wondering which one will yield a better response because you’re worried about tumor burden or the patients are currently being treated with 2 other things. The PSMA, the lutetium arm, had a higher PSA [prostate specific antigen] response compared with the cabazitaxel arm, approximately 66% vs 37%. The hazard ratio was approximately 0.6 or 0.63. So, the trend is that the lutetium arm might be slightly more active, but we’ve got to delve into that a little more. We’re in the third line now. We now have some wonderful tools to help patients fare better, but still, the completion of treatment, or at least the intended treatment, is not easy. With the lutetium compound, you would want to complete at least 6 cycles to ensure [the patient received] it all. And in that trial, only 46% of patients got all 6 treatments. The cabazi [cabazitaxel] arm had 10 treatments for completion, which is a little more, but only 36% of patients completed 10 treatments. So it’s not a true comparison—“this compared to that.” It’s more of a broad stroke—“Well, this is helpful, at least it’s been put in trial.” There is more that we have to learn and we know there are probably other factors at play, when we look deeper, that might indicate one group is better than the other. But I’m not sure how you’re incorporating that data into your practice.

Tanya Dorff, MD: Yes, therapy was helpful. Because cabazitaxel, as we’ve been discussing, is really an active comparator. Whereas in the VISION trial [NCT03511664], the control arm was not getting much and we think it’s very helpful. Some of the patients in the VISION trial had both abi [abiraterone]and enza [enzalutamide].

Elisabeth Heath, MD, FACP: Yes.

Tanya Dorff, MD: On the control arm, patients are getting another AR [androgen receptor]-targeted agent, but we know that’s not going to be successful. Some of it was second.

Elisabeth Heath, MD, FACP: Yes, supportive care.

Tanya Dorff, MD: Right. The fact that VISION was positive is so meaningful. But the therapy trial is what made me believe the lutetium PSMA was effective. Even though it was a smaller trial, just the proof of principle [was encouraging], that head-to-head with cabazitaxel, we got similar survival rates. And we know cabazitaxel impacts survival. To me, that was meaningful. When you look at the fact that the response rates were higher, you must remember that researchers held the patients to a higher standard on their PSMA PET [positron emission tomography] scans to get into the trial, compared to [the requirements for] VISION. For VISION, a patient had to have 1 lesion, be PSMA positive, and have no dominant-negative soft-tissue lesions—a lesion that was above liver background, which typically is SUV [standardized uptake value] in the low single digits, perhaps 3 or 4, or even 2. But on the therapy trial, they had to have at least 1 lesion with an SUV max of 20. Given the way we’re using lutetium PSMA, we may not see those response rates, and they might look more like the ones from the VISION trial. The conclusion I drew from the 2 trials is, it’s great that we have another tool that extends survival and works by a different mechanism, but we [continue to] have both tools and there may be some patients where we feel more comfortable using one over the other, although hopefully, we’ll use both. The goal is for patients to access as many life-extending treatments as possible, so if they are given cabazitaxel first, they can still get the lutetium PSMA and [vice versa]. Looking at the PSMA PETs is going to be a big learning curve. Things like visceral metastases, liver mets [metastases]—are they going to do better with chemotherapy? Maybe a more aggressive variant would do better with cabazi carbo [cabazitaxel plus carboplatin] than with the lutetium PSMA. I think there are still some unanswered questions.

Elisabeth Heath, MD, FACP: At our tumor board, the number of PSMA PET scans that are discussed now are astronomical. Since the approval several months ago, we’re like this [gesture indicating an incline] in terms of the trajectory of the number of scans, and yet each one has a different read. “For that one, the SUV is 12, but it’s 9 mm on that lymph node, what are we going to do with that? Wow, that’s really hot.” Or, “Now there are 15 bone areas that would’ve never lit up because they’re so tiny, but they’re positive at an SUV of 4.” Now we’re seeing all these weird permutations; [it makes us question,] is it real or not real? It’s hard to not see it, but we need to get better information on the tests that lead us to this treatment, whereas with the cabazitaxel, [that information isn’t available yet]. You and I might say, “Gee, I want the PTEN loss and the TP53 and RB1,” even though that’s not necessary.There’s a practicality with chemotherapy that is a good thing, at least in terms of making treatments available for patients. That notwithstanding, there is the resource issue: we still probably don’t have the best idea of who should get lutetium-177. [But the good news is, there will be] more studies, a more in-depth look at who should get what. We didn’t even talk about what to do with the genomics when you’re thinking about the lutetium; do we throw the whole thing out or do we try to put it in before or after? [We] don’t know; we don’t have that data.

Tanya Dorff, MD: We need so much more data. We do know that PSMA PET scans seem to be a tool that can help us select patients, narrowing down the criteria we will look at and be able to say, “This patient will do better with the radiopharmaceutical, but this other patient may not do as well and we should [consider] chemotherapy as the first line of treatment.” The sooner we use an effective therapy, the better we are at not letting the cancer get too far ahead of us. We want to be able to differentiate the patients who might be able to benefit from one vs the other.

Transcript edited for clarity.

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Evan Y. Yu, MD, professor, medical oncology, assistant fellowship director, University of Washington School of Medicine, professor, Clinical Research Division, clinical research director, Genitourinary Medical Oncology, Fred Hutchinson Cancer Center, medical director, clinical research support, Fred Hutchinson Cancer Research Consortium
Michael A. Carducci, MD, professor of oncology, AEGON Professor of Prostate Cancer Research, Johns Hopkins Medicine
Michael S. Cookson, MD, MMHC, professor, chairman of urology, University of Oklahoma College of Medicine, chief, Urology, Stephenson Cancer Center
Andrei H. Iagaru, MD, professor of Radiology - Nuclear Medicine, chief, Division of Nuclear Medicine and Molecular Imaging, Stanford University Medical Center
Jeremie Calais, MD, MSc, assistant professor of nuclear medicine and theranostics, David Geffen School of Medicine, University of California, Los Angeles (UCLA), UCLA Health,
Tanya Dorff, MD, medical oncologist, associate clinical professor, Department of Medical Oncology & Therapeutics Research, City of Hope
Matthew Rettig, MD, chief, hematology-oncology, VA Medical Center, professor of medicine and urology, David Geffen School of Medicine, University of California, Los Angeles (UCLA) Health
Tian Zhang, MD, MHS
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