Systemic Therapy Update on 177Lutetium-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer: ASCO Rapid Recommendation Update

An interview with Dr. Rohan Garje from Miami Cancer Institute in Miami, FL, lead author on "Systemic Therapy Update on 177Lutetium-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer: ASCO Rapid Recommendation." Dr. Garje reviews the new evidence and the latest recommendation update for the use of 177Lu-PSMA-617, a radioligand therapy in patients with PSMA-positive mCRPC, along with it's implications for clinicians and patients. For more information, visit www.asco.org/genitourinary-cancer-guidelines.   TRANSCRIPT Brittany Harvey: Hello, and welcome to the ASCO Guidelines Podcast series, brought to you by the ASCO Podcast Network; a collection of nine programs, covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one at: asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Rohan Garje from Miami Cancer Institute in Miami, Florida, lead author on, ‘Systemic Therapy Update on 177Lutetium-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer: ASCO Rapid Recommendation’. Thank you for being here, Dr. Garje. Dr. Rohan Garje: Absolutely. Thank you so much for having me, Brittany. Brittany Harvey: Great. And first, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest policy is followed for each guideline. The full Conflict of Interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Garje, do you have any relevant disclosures that are directly related to this guideline topic? Dr. Rohan Garje: Yes. I have received institutional research funding from Pfizer, Amgen, Endocyte, and AAA, who have drugs for the treatment of prostate cancer. Brittany Harvey: Excellent. Thank you for those disclosures. Then getting into the content of this guideline update, what prompted this rapid update to the ‘ASCO Guideline on Systemic Therapy in Men with Metastatic Castration-Resistant Prostate Cancer’, which was previously published in 2014? Dr. Rohan Garje: Since 2014, there are several new drugs that have been approved for prostate cancer management. And most recently in March 2022, FDA has approved 177Lutetium-PSMA-617 for patients with PSMA scan-positive metastatic castration-resistant prostate cancer. This led to the team from ASCO to develop this new rapid recommendation update. Now, this approval actually has been based on the efficacy data published in VISION clinical trials. To give you a little background about Lutetium, it is a novel β-energy-emitting radioligand therapy. In this particular study, this agent was combined with best standard of care, and compared to best standard care alone, in men with metastatic castration-resistant prostate cancer, who had a positive PSMA scan. Briefly, the study was both clinically and statistically positive, and has shown improvement in both overall survival and radiographic progression-free survival. The median overall survival was about 15.3 months with the combination therapy, compared to 11.3 months with the standard care arm. Brittany Harvey: Great. And then based off this new evidence and the new approval from the FDA for 177Lutetium-PSMA-617, what are the updated recommendations from the guideline panel? Dr. Rohan Garje: The panel recommends the use of 177Lutetium-PSMA-617 as a treatment option in patients with PSMA PET/CT positive metastatic castration-resistant prostate cancer, who have been previously treated with at least one line of androgen receptor pathway inhibitor, and at least one line of prior taxane-based chemotherapy. Brittany Harvey: Great. And then, what should clinicians know as they implement the use of this drug and this new recommendation by the guideline panel? Dr. Rohan Garje: A very good question. It is important to select patients based on a positive PSMA scan. That is, all the metastatic lesions should be positive on the PSMA scan, and there should not be any large lymph nodes or visceral organ metastatic disease that are PSMA negative. Additionally, physicians can use Gallium 68 PSMA-11, or F-18 piflufolastat as radiotracers for PSMA scan to determine eligibility. Additionally, there are several other factors that need to be considered, such as: the patient should have baseline good blood counts, as well as renal function to be eligible for this therapy, as this treatment has a potential to cause myelosuppression and impairment of renal function. The most common side effects associated with this drug are fatigue, dry mouth, dry eyes, and nausea. The treatment in general is for four to six cycles. Each cycle is for every six weeks. The fifth and sixth cycles should be considered only if patients are responding well to the therapy and have no significant toxicities. It is also important for the physicians to note that there are several additional treatment options for patients with metastatic castration-resistant prostate cancer, who had prior anti-androgen docetaxel therapy. They include; cabazitaxel, PARP inhibitors for patients who have mutations in DNA repair, gene mutations such as BRCA1 and BRCA2, and immunotherapy with pembrolizumab for patients with MSI-high status, or tumor mutation burden greater than 10. Brittany Harvey: Thank you for describing that nuance behind the recommendations. So then, in addition, how does this update impact patients with metastatic castration-resistant prostate cancer? Dr. Rohan Garje: 177Lutetium-PSMA-617 is the first radioligand therapy approved for the treatment of prostate cancer. Previously, we had Radium-223 as a radiopharmaceutical, but this particular agent is unique in the sense, it is a radioligand therapy where it is chelated to PSMA. So, it is very targeted therapy which works for both bone and visceral organ metastasis. So, this is an exciting treatment option for patients, as it has been shown to have improvement in overall survival. This adds to the current treatment choices of anti-androgens, chemotherapy, as well as targeted therapies for prostate cancer patients. Brittany Harvey: Great. It's exciting to have a new treatment option for patients. So then finally, what are the outstanding questions regarding systemic therapy for metastatic castration-resistant prostate cancer? Dr. Rohan Garje: We are at an exciting stage in the management of prostate cancer. In the last decade, we have seen several new drugs; some are specific targeted agents, some are specific immunotherapy agents. Now, we are entering into this realm of radioligand therapy, which is very exciting. There are several other novel radioligand therapies such as; actinium, thorium, lead, which are being evaluated in the treatment of prostate cancer. So, in the next several years, we will see several new drugs that have been developed. In addition, there are other agents called T-cell-engaging therapies, which are being evaluated to improve the outcomes. So, the last decade definitely has seen a lot of new improvements, but we are so excited that several new treatment choices are now available for patients, and several are in clinical evaluation. So, the future is bright for the patients with prostate cancer, where we have several new treatment choices to improve their outcomes. Brittany Harvey: It sounds like an exciting time for developments in prostate cancer. So, I want to thank you so much for your time today, Dr. Garje, and thank you for all of the work you did to update this guideline. Dr. Rohan Garje: Thank you so much. I really thank ASCO leadership and the team for giving me this opportunity, and thank you, Brittany, for hosting me on this podcast. Brittany Harvey: And thank you to all of our listeners for tuning into ASCO Guidelines Podcast series. 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