Cabazitaxel for the Treatment of mCRPC

Transcript:Nicholas Vogelzang, MD: One of the underlying themes of prostate cancer has been maintaining quality of life. There are a lot of patients who are very afraid of getting chemotherapy. I mentioned that figure of 4.8% getting chemotherapy in the hormone-sensitive phase. Even overall during the entire course of prostate cancer, many patients refuse chemotherapy, and perhaps less than 50% even of all patients get chemotherapy. Is it really a quality-of-life issue, or is it just a fear factor that we haven’t figured out yet?

Daniel Petrylak, MD: It’s a fear factor because of the prevailing wisdom what people see on television and what they may see from their friends who may receive completely different forms of chemotherapy than what we’re administering. One of the key things to emphasize is that talking about adverse effects early, communicating with your doctor, communicating with the nurse practitioner who works with you is crucial in managing the adverse effects. If we catch a fever early, if we catch fatigue early, we may be able to do some things to fix those so that the patient can tolerate chemotherapy better.

What I’ve seen over the years is improvements in bone pain, which people don’t really capture. Performance status in somebody who is doing poorly to begin with actually can improve. And it’s very difficult to select that patient out beforehand, but I’ve seen dramatic improvements in quality of life as time has gone on. The crucial thing is a good relationship between the patient and the physician, carefully explaining what to expect, carefully explaining what adverse effects to expect, and also emphasizing the positive that you may have an improvement in quality of life as you treat it.

Nicholas Vogelzang, MD: My impression is that docetaxel still is rough on patients.

Daniel Petrylak, MD: Yeah.

Nicholas Vogelzang, MD: There’s still hair loss. There’s still neuropathy. Do you see any difference in the cabazitaxel? What about the dose of cabazitaxel? And what about the issue of the CARD trial, where cabazitaxel and the second-generation hormones were impaired?

Daniel Petrylak, MD: Well, as much as I hate to say it, I think cabazitaxel is a better drug than docetaxel. Cabazitaxel is easier tolerated.

Nicholas Vogelzang, MD: Particularly at the lower dose.

Daniel Petrylak, MD: Patients don’t have the same degree of asthenia and fatigue that they do with docetaxel. Also, neuropathy is an issue. I recently took care of a patient who was a violinist, and we gave him cabazitaxel up front because I was afraid he was going to lose his sensation playing his instrument.

Nicholas Vogelzang, MD: And you got the insurance to cover it.

Daniel Petrylak, MD: The insurance covered it. They actually accepted the rationale behind it. I think it’s a better drug from that standpoint. It’s better tolerated than docetaxel is. Some patients, you’re absolutely right, can get pretty beaten up by docetaxel, particularly as you go further down the line. The CARD trial had some interesting observations. Karim Fizazi has presented some data looking at the quality of life of abiraterone or enzalutamide versus cabazitaxel in that particular study. Didn’t see much of a difference between those, so that tells us the activity of the drug may actually be helping overcome some of the adverse effects. And you get the same result with ABI [abiraterone] or ENZA [enzalutamide] as you do with cabazitaxel. The fatigue with enzalutamide is significant in some patients, and that has to be watched very carefully.

Nicholas Vogelzang, MD: The other drugs we use that are easily tolerated include sipuleucel-T and radium 223 dichloride. Is starting with sipuleucel-T and radium sort of a first-grade look at quality of life? Does this help the patients get ready?

Daniel Petrylak, MD: Yeah, it helps the patients get ready, and there are different situations that we can use this in to help patients maintain a good quality of life. I do see PSA [prostate-specific antigen] declines with radium. I’ve seen that. It’s actually very nice when you see it because your patients don’t expect that at that particular point. With sipuleucel-T we potentially can delay patients going on other treatments afterward. I’ve seen patients’ PSA flatten out over time, although you may not see declines. The drug does have a role in this disease. It’s about transitioning to more aggressive treatments later on, you’re absolutely right about that.

The disappointing thing about the studies with radium is that there was that observation that there was a higher fracture rate when you combine that with abiraterone. We know that adding bone anti-resorptive agents may abrogate that particular observation. I would love to try to move radium up front more by combining it with novel anti-androgens.

Nicholas Vogelzang, MD: Well, my practice has been to move radium as early as I can. It’s always a challenge to know whether to give sipuleucel-T first or radium first. And the whole integration of second-generation AR [androgen receptor] agents has been disappointing that it didn’t show a survival advantage.

Daniel Petrylak, MD: Very good point.

Nicholas Vogelzang, MD: But you still have to give the drugs because they’re life prolonging. Even though they may not be synergistic in prolonging life, they certainly independently prolong life.

Daniel Petrylak, MD: My goal in treating patients is to make sure they receive every class of drug that we have available to them, whether that is immune therapy, next-generation anti-androgens, DNA-damaging agents like radium, the PARP inhibitors, and the chemotherapeutic agents as well. If we can do that, then I feel that I’ve accomplished the best-possible care for my patients in this situation.

Nicholas Vogelzang, MD: In the long run their quality of life is maintained for longer periods of time.

Daniel Petrylak, MD: Exactly. And the quality of life as well. I was thinking last night. I was out with Maha Hussain and Tia Higano, good friends from SWOG, and we were talking about all the interesting people we’ve run across in this business. And I think back to that review about chemotherapy in prostate cancer and the survivals being only 12 months at that time. Look how far we’ve come—3 years, 4 years these patients are living, as opposed to where we were at that time. We’ve made a huge amount of progress in this disease, and it’s from using these drugs and integrating them properly.

Nicholas Vogelzang, MD: It seems to me that we still need better education. I still have patients who are refusing chemotherapy. I still have patients who aren’t getting all the optimal therapies, so we still need to do a better job not only educating the patients but also all medical oncologists.

Daniel Petrylak, MD: Also, embracing populations that may not have had the opportunity to get these treatments before. There was a very telling statistic that was published in JCO [Journal of Clinical Oncology] in a letter a couple of years ago that the number of African Americans participating in clinical trials is about half of what you would expect from the projected data of the number of patients having castrate-resistant disease. That’s our fault. We need to educate patients better. We need to embrace them and embrace people in the community and make sure that they understand what’s out there.

Nicholas Vogelzang, MD: Also, we have data suggesting that docetaxel in African American patients is actually more effective than you would expect. And now we have this preliminary data on sipuleucel-T suggesting again that the African American population has an altered immune response and longer benefit to sipuleucel-T. We really need to communicate better with our doctors who treat these patients but also with the patient populations.

Daniel Petrylak, MD: The question is how do we best do that, and there are a number of answers to that. It’s exposing people to media, to other types of venues. I often say that in an era when we have more tools for communicating with one another, we communicate less than we ever did. It’s incumbent on us to communicate with our patients, as well as our colleagues, and let them know what’s happening.

Nicholas Vogelzang, MD: Thanks, Dan. I appreciate that.

Transcript Edited for Clarity