Doctors Discuss Targeted Treatments for Prostate Cancer Subtypes

discussion question

• Have you ever used carboplatin and cabazitaxel (Jevtana)? In what scenarios have you used it?

Mufadar Hamade, Maryland: Prostate Cancer Has Subtypes That Are Not Prostate-Specific Antigen [PSA] Carboplatin worked more aggressively against more visceral metastases, and I used carboplatin on multiple occasions. [to treat these patients]. I think it would be best for him to use carboplatin earlier in combination with cabazitaxel, and even sooner than his line 3 or 4 treatment.

Joshua Lang, MD, M.S.: As you said, there are other aggressive subtypes of prostate cancer. One is neuroendocrine prostate cancer.¹ Some doctors also use the term advanced atypical prostate cancer. Neuroendocrine is classically defined as having synaptophysin or chromogranin A expression. [CgA]If you’re doing biopsies for visceral disease, including liver, lungs, and more, often… that’s not all. [do I need to get] Sufficient tissue for next-generation sequencing [NGS]As well as synaptophysin or CgA staining to look for neuroendocrine prostate cancer signatures. This is useful to help prepare the patient.

This is a situation where platinum should be used [therapy] For example, whether it’s carboplatin, cabazitaxel, or cisplatin/etoposide, it should be done sooner rather than later. This is neuroendocrine prostate cancer or bulky lymphadenopathy >5 cm with lytic disease and a short duration of response to low PSA or a short duration of response to hormonal therapy, looking for a high-grade variant This is a very important point for

discussion question

• Do you administer cabazitaxel to patients who have not tolerated docetaxel well?

Lang: Several different PEACE-1-based treatment options are available for patients with metastatic prostate cancer at first diagnosis. [NCT01957436] or aracens [NCT02799602] On trial…we are still on docetaxel. [this] Usually used in combination with abiraterone [Zytiga] or darolutamide, but some patients omit docetaxel and undergo antigen deprivation therapy [ADT] such as abiraterone.If those patients develop castration-resistant prostate cancer [CRPC], the key question is whether docetaxel should be used first or whether cabazitaxel could have been used as well. Cabazitaxel is FDA-approved and² Addition of platinum may also be considered at that time, especially if the patient has other high-risk features such as genomics or liver metastases.

In the CRPC setting, if a patient has metastatic disease and is already receiving docetaxel, then it is easy to continue on cabazitaxel. From a payer’s perspective, I don’t think they have a hard time getting compensated for cabazitaxel compared to docetaxel.The other side is if [a patient] Had a prostatectomy or treatment for the primary prostate [tumor]After that, they only received ADT and now treat CRPC with enzalutamide and others. Should I use docetaxel together? I still tend to choose docetaxel first and cabazitaxel for rechallenge as a second line to taxane therapy. However, if you have other risk factors, such as those with baseline peripheral neuropathy, cabazitaxel should be used first instead of docetaxel.

Dr. Anastas Probatas: Has anyone considered second-line cabazitaxel in patients on prior triplet therapy, or can the data be extrapolated?

Lang: Abiraterone with or without cabazitaxel is being studied in clinical trials by the ECOG Working Group in patients receiving the dual regimen of ADT and docetaxel.³ We have started that test at our facility as well. Registration is complete. I look forward to having the data to report. [soon]. In my practice, cabazitaxel is very effective in that setting.Highly effective, well tolerated, no adverse events [AEs] Exceeds what is already expected from other clinical trials.

Christos Kyriakopoulos, MD, M.S.: There was a retrospective analysis of studies examining the role of docetaxel in hormone-sensitive diseases.^Four They found that in patients who had previously received docetaxel, rechallenging with docetaxel resulted in a worse response than in patients who had not received docetaxel. However, although technically patients who have previously received docetaxel can receive docetaxel again, I think cabazitaxel is probably the better choice.

discussion question

• How would you advise a patient who fears chemotherapy?
• What about infusion and oral options and their tolerability profiles?

Dr. Betty Siobhanu: For patients undergoing hormonal therapy, if they are already taking oral medications and have a short duration of response, they are more likely to accept chemotherapy in that scenario than if they were only offered chemotherapy in the first place. think. The question I have is how to choose between triplet therapy and cabazitaxel for patients. [with CRPC] WHO IS HIGH RISK?

Lang: Lifelong leuprolide or ADT in CRPC settings.at that point, especially if someone is progressing on abiraterone or enzalutamide [Xtandi]So I lean towards docetaxel or cabazitaxel, especially in patients with peripheral neuropathy. If the internal organs are involved, I would consider adding carboplatin with a platinum doublet to those patients, especially those with neuroendocrine disorders. As for some of the tolerability issues, my experience is that nausea and vomiting are very rare these days. I think the medications we are on before treatment and treatment management are much better than they were when I finished my fellowship, so nausea and vomiting are relatively rare.it happens [though]should be proactively addressed.

I am talking to my patients about the infection risk of neutropenia [being] My biggest concern about chemotherapy. They have our triage number. They know they will call us if we can get them treated right away. [intravenous] Antibiotics work well for everyone. This helps build a safety her net for the patient and the patient can call him 24 hours a day, 7 days a week if needed.I am from now on [use] Granulocyte colony-stimulating factor prophylaxis is also possible. Unfortunately, these days, every insurance company seems to have their own preferences as to whether or not they allow prescriptions, and this presents a challenge. In any case, I think it is very important, especially for patients, to have access to it. [if they’re on] Cabazitaxel.

Dr. Sangyu Bae: If [a patient] was hiding BRCA mutation [in their disease]are considering a PARP inhibitor, [but] My patient has progressed on enzalutamide, do you want to use it before or after chemotherapy?

Lang: One of the things I try to do in my clinical practice is to try to send biopsies whenever possible when a patient has metastatic disease. We will also send you a germline sample, BRCA1/2or other relevant mutations therein [DNA damage response and repair] clump of genes. There are new data demonstrating its use with olaparib. [Lynparza]or niraparib [Zejula] Even if you have androgen receptors, signal blockers are better, especially for people who: BRCA2 mutation.^5,6 So when I treat patients with metastatic disease, I try to find out if they have metastatic disease. BRCA1/2 For example, mutations occurred even before we started Abiraterone. If so, we will see if it gets approval for use with olaparib. If someone is already on abiraterone and has progressed, I would choose a PARP inhibitor directly over chemotherapy in that case.

^References:

^{1. Yamada Y, Bertrand H. Clinical and biological features of neuroendocrine prostate cancer. Curr Oncol Rep. 2021;23(2):15. Doi: 10.1007/s11912-020-01003-9}

^{2. Palla CJ, Antonarakis ES. Cabazitaxel: A novel second-line treatment for metastatic castration-resistant prostate cancer. Drug death devel sir. 2011; 5:117-24. Doi: 10.2147/DDDT.S13029}

^{3. Lynn J, Den RB, Greenspan J, et al. A phase I trial of weekly cabazitaxel combined with intensity-modulated radiation and androgen deprivation therapy for the treatment of high-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2020;106(5):939-947. doi:10.1016/j.ijrobp.2019.11.418}

^{4. Clark NW, Ali A, Ingleby FC, et al. Addition of docetaxel to hormone therapy in low- and high-burden metastatic hormone-sensitive prostate cancer: long-term survival results from the STAMPEDE trial. Ann Ongol. 2019;30(12):1992-2003. doi: 10.1093/annonc/mdz396}

^{5. De Bono J, Mateo J, Fizzazi K, et al. Olaparib for metastatic castration-resistant prostate cancer. N English J Med 2020;382(22):2091-2102. Doi: 10.1056/NEJMoa1911440}

^{6. Chi KN, Rathkopf D, Smith MR, et al. Magnitude Chief Researcher. Niraparib and abiraterone acetate for metastatic castration-resistant prostate cancer. J Clin Onkor. 2023;41(18):3339-3351. Doi: 10.1200/JCO.22.01649}