Case 3: Metastatic Castrate-Resistant Prostate Cancer
Alicia Morgans, MD, MPH, presents the case of a 67-year-old man with metastatic castration-resistant prostate cancer.
Alicia Morgans, MD, MPH: Let’s move on to our final patient case. This is another take on a case we talked about earlier but with a little twist. I’m going to review this case, and then Ulka will walk us through some data. Just to remind everyone, this is a 67-year-old gentleman who came into his primary care doctor with reduced urinary flow and some hematuria. He had pain on his left hip, and he had a past medical history that was relatively benign, just some hypertension that was quite well controlled. His PSA [prostate-specific antigen] was 7.4 ng/mL, and he had a prostate biopsy that showed Gleason score 8 and 4+4 prostate cancer and a bone scan that showed he had metastatic lesions in the left pelvis and the left lobe of the lung. He had an ECOG performance status of 0, with quite functional, well-controlled comorbidities. He started treatment with abiraterone ADT [androgen deprivation therapy] and, of course, prednisone when he was taking the abiraterone. PSA decreased to 0.2 ng/mL, so he had a nice response, but 13 months later, he started to develop a rising PSA, suggestive of a progression. PSA peaked at 5.7 ng/mL when he underwent PET [positron emission tomography]–CT, which showed enhancing lesions in the lung and the ribs. At that time, he initiated treatment with docetaxel but stopped his treatment with docetaxel after 2 cycles because of intolerance, and this was at that time grade 2 neuropathy.
Phil, I’d love to hear your thoughts. This is a patient who has metastatic disease. He has a progression of disease and was able to get a PET-CT. Perhaps that was on a clinical trial, but maybe it was for some clinical purpose. What are your thoughts? Does that change management as we talked about in terms of always having a purpose for a test as we’re ordering it?
Phillip J. Koo, MD: This is always the question that comes up over and over: why you did it, and all of a sudden you see more. What do you do then? We’d all agree that we want to follow the evidence as closely as possible. Unfortunately, or fortunately, the evidence we have is based a lot on conventional imaging. When you’re entering outside that space and making decisions based on new information you have on a PSMA PET, it might be the right decision, but you’re in a data-free zone. This is where a lot of times it’s a matter of building those teams and having those multidisciplinary discussions. That may not always give the right answer, but it’s backed by multiple perspectives that can hopefully lead to the best outcome for the patient.
Alicia Morgans, MD, MPH: As I think about patients in my clinic, and I’m trying to get prior authorizations to get some of these imaging modalities, I try to hold on to each of these until there’s a clinical reason to get this particular test, because I may only be able to get 1 or 2 in the course of this patient’s illness. Maybe I’ll be able to get more, but I don’t bank on that. Just make sure you’re judicious with the ordering of this particular modality, especially because it’s new. Hopefully in the future, we’ll be using PSMA PET scans to very easily follow disease progression and change over time, but it’s still in flux at this point. Ulka, from your perspective, how common is it for a patient to not really tolerate chemotherapy with docetaxel? Is that something you see regularly?
Ulka Vaishampayan, MD: No, but there are some odd patients who do have significant toxicity and intolerance, and a lot of it occasionally may be related to neuropathy, but frequently it’s related to systemic or cytopenias that lead to infection, hospitalization, etc.
Alicia Morgans, MD, MPH: Agreed. Thank you. If you weren’t able to use docetaxel for this patient because of intolerance and you’d already used abiraterone, Tanya, what are you thinking about in terms of treatment for this individual?
Tanya Dorff, MD: One would like to have the option of cabazitaxel given the data showing the efficacy in the CARD study, as well as the FIRSTANA trial, which we’ll look at in a moment. It can be challenging because most of the time it’s restricted to the postdocetaxel setting. When I have a patient with neuropathy or poorly controlled diabetes, and I’m thinking that cabazitaxel would be a better fit for the patient, it can be hard to get that drug for them without going through the docetaxel. That’s a challenge.
Alicia Morgans, MD, MPH: That’s absolutely true. In this case, the patient has had a couple of cycles of docetaxel. To your point, it’s important for us to understand differences that might exist between docetaxel and cabazitaxel in the adverse effect profile. The first trial does provide some insight for us. Ulka, can you run us through FIRSTANA?
Ulka Vaishampayan, MD: FIRSTANA was a study that randomized patients to receive a docetaxel standard dosage of 75 mg/m²every 3 weeks along with prednisone 10 mg per day. The patients were randomized to 2 other arms of cabazitaxel, either cabazitaxel 20 mg/m²starting dose every 3 weeks or 25 mg/m². At the time this was standard dose evaluated in the TROPIC trial, which led to the FDA approval of cabazitaxel.
The patient population was all patients with metastatic CRPC [castration-resistant prostate cancer], performance status 0 to 2 with no prior chemotherapy, no brain metastases, no immediate spinal cord compression, etc. Patients were treated until progressive disease or unacceptable toxicity. One thousand one hundred sixty-eight patients were randomized. If you look at the efficacy results, this study showed us that survival was fairly similar across each arm. The median survival, if you look at cabazitaxel 20 mg/m², is 24.5 months—25.2 months with the 25-mg cabazitaxel dose and 24.3 months with docetaxel 75 mg/m². You wouldn’t be compromising survival outcomes if you switch from docetaxel to cabazitaxel because of intolerable toxicity or certain reasons. Otherwise, progression-free survival was pretty similar, 4.4 months median, 5.1 months with cabazitaxel 25 mg, and 5.3 months with docetaxel.
The other thing that came out of this study is that cabazitaxel 20 mg/m² is a very standard, easier dose to use with the comparable efficacy and an improved toxicity profile. Looking at the response rates, PSA response rates also were fairly similar with no major differences between the 3 arms and similarly for pain progression-free survival. Also median was 8 months with cabazitaxel, 27.3 months with cabazitaxel 25 mg, and 10.1 months with docetaxel. In terms of other health-related quality-of-life markers, there was a pretty similar efficacy noted across the 3 arms and patients with pain progression, the median time to pain, as well as a pain response. There was no difference among the 3 arms. Based on this, switching from docetaxel to cabazitaxel, especially for patients who were intolerant of docetaxel, has been incorporated into the NCCN [National Comprehensive Cancer Network] Guidelines.
Alicia Morgans, MD, MPH: That makes sense if there are differences in tolerability, particularly when we use the similarly effective cabazitaxel 20 mg/m² dose.
Transcript edited for clarity.
