PracticeUpdate: Oncology - Winter 2018

MultipleMyeloma at ASCO 2018 Interview with Rafael D Fonseca MD by Farzanna S Haffizulla MD, FACP, FAMWA Dr. Haffizulla : Can you highlight for us some of the most important studies in the multiple myeloma arena this year? Dr. Fonseca: Well it’s no surprise of course, we’re getting updates with regards to the CAR T-cell work and those are very, very important studies that continue to show the benefit of this approach for patients with relapsed and refractory myeloma, particularly for those who have exhausted all therapies. There were some practical studies like this, administration of carfil- zomib once versus twice per week, and also an important study looking at the combination of pomalidomide, borte- zomib, dexamethasone; so that versus bortezomib and dexamethasone, and this just builds on the body of knowledge that we have that truly allows us to engage in better treatment for our patients. Dr. Haffizulla: Are any of these studies yet practice changing or ready to translate into clinical practice? Dr. Fonseca: I think the most pressing one is the one related to the CAR T-cell ther- apy. The CAR T-cell results that were presented here from the Bluebird clinical trial were really impressive, is a word that should be used because of the patients who are responders, pretty much they all attained an MRD negativity, which is absolutely something that we have not seen in the past. These treatments are moving from the fairly advanced patient, but the question now would be at what point are we going to start thinking about this type of interventions? Earlier, perhaps, even as frontline therapy for someonewhomight have high-risk dis- ease. I tell my patients that we’re treating now that we diagnose, you knowwe want to get the time right now with the treat- ments that we have available so we “iron the wrinkles” of CAR T-cell therapy, the management of CRS, etc. But I think this is something that has already changed prac- tice when it comes down to other B-cell neoplasms, but myeloma is knocking on that door. www.practiceupdate.com/c/69173 CONFERENCE COVERAGE 26

ASCO 2018: Updates on PARP Inhibitors in Prostate Cancer Interview with Neeraj Agarwal MD by Sumanta Kumar Pal MD

Dr. Agarwal, a specialist in genitourinary cancer, is Associate Professor in the Department of Internal Medicine (Medical Oncology) at Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.

Dr. Pal: Neeraj, I wanted to pick your brain a little bit on prostate. We’re seeing a lot of data here at this meeting related to PARP inhibition, genomics, etcetera. Tell us about the status of PARP inhibitors in prostate cancer now. Dr. Agarwal: I think the whole interest about PARP inhibitors came from the findings reported over the last 2 years that many of these advanced prostate cancer patients harbor mutations in their DNA repair genes, either in germline or in their tumors. And just to give a brief background of DNA repair genes, tumors which harbor these mutations really cannot repair double- strand breaks. It does make them highly dependent on the single strand break repair pathways, which are regulated by the enzyme, PARP, poly (ADP-ribose) polymerase. And there we have a potential target for drug devel- opment because there are many PARP inhibitors, which are already developed and approved in ovarian cancer [and], one approved in breast cancer. Again, they’ll be utilized in these patients who are harboring these mutations or tumors. And that pro- vides the rationale for the study I have the privilege of leading with Dr. Karim Fizazi. This is a phase III global registration trial, which is going to accrue patients with newly diagnosed castrate-resistant metastatic prostate cancer and which harbor muta- tions in DNA repair genes, and their tumors are in their germline. There we randomized the standard of care enzalutamide versus enzalutamide plus talazoparib and just a " If you see any patients with metastatic castration- resistant disease that’s newly evolved, it sounds

little background on talazoparib. This is a PARP inhibitor like any other PARP inhibitor, but there is another unique mechanism of action of PARP trapping; trapping the PARP on the DNA. At least based on in vitro data, talazoparib may be more efficacious…clini- cal speaking it may bemore efficacious than other PARP inhibitors. The primary endpoint is overall survival and progression-free sur- vival. So we’re really looking forward to positive results on this trial. Dr. Pal: That’s really exciting and [it] gives us a little sense of the eligibility for this study. Do patients have to have mutations in DNA repair genes? Can they have [had] prior therapy for instance? Dr. Agarwal: Yes, patients have to have DNA repair gene ablated mutations either in the germline or in the tumors. And that’s why I don’t wait for them to become castrate-re- sistant. I screen them for these mutations when I actually see them for the first time, so that I’m ready for these interventions when they actually develop castrate-resist- ant disease. Dr. Pal: What about prior chemotherapy? Can they have [had] abiraterone, etc.? What are some of the eligibility there? Dr. Agarwal: These patients much have a newly diagnosed castrate-resistant disease. So they must have progressed on the first-line therapy. They cannot have any lines of therapy in the setting of castrate- resistant prostate cancer. Dr. Pal: Well, that’s really, helpful. If you see any patients with metastatic castration-re- sistant disease that’s newly evolved, it sounds like this is a fantastic trial for your patients provided that they have DNA repair alterations.

Dr. Pal is Associate Professor in the Department of Medical Oncology & Therapeutics Research, and Co-Director of the Kidney Cancer Program, City of Hope, Duarte, California.

like this is a fantastic trial for your patients provided that they have DNA repair alterations. "

www.practiceupdate.com/c/69247

PRACTICEUPDATE ONCOLOGY