Practice Update: Oncology

Q & A 34

New Data on Immunotherapy for Bladder Cancer: Part 1 Interview with Petros Grivas MD, PhD by Farzanna S Haffizulla MD, FACP, FAMWA

Dr. Grivas is a medical oncologist in Cleveland, Ohio, specializing in genitourinary cancer. He is an associate staff member in the Department of Department of Hematology/Medical Oncology of the Taussig Cancer Institute of the Cleveland Clinic Foundation.

PracticeUpdate’s Dr. Farzanna Haffizulla spoke with Dr. Petros Grivas about the recently published results of the phase II trial on atezolizumab in advanced urothelial carcinoma. Dr. Grivas is on the staff of the

Cleveland Clinic in Cleveland, Ohio. Dr. Haffizulla: I wanted to first talk about the results of a phase II study published last month in The Lancet of atezolizumab in patients with locally advanced and meta- static urothelial carcinoma who progressed following platinum-based chemotherapy. 1 Will you discuss the results of the study and its impact in treating metastatic urothelial carcinoma? Dr. Grivas: I would be happy to. This is a landmark study, a phase II trial that was launched recently. I have to say I was impressed with how quickly it enrolled patients. This was a single-arm, not ran- domized trial of the immune checkpoint inhibitor atezolizumab, which is directed against the PD-L1 immune checkpoint, one of the brakes of the immune system. The trial tried to evaluate the efficacy, activity, and safety of atezolizumab in patients who either had progressed during or after plat- inum-based chemotherapy or who were ineligible to receive cisplatin-based chemo- therapy, which seems to be the standard of care as first-line treatment for those patients with metastatic urothelial carci- noma. The primary endpoint of the study was to evaluate the overall response rate, tumor shrinkage, as we say in lay terms; and, of course, it had a variety of other end- points. The results of the study that were recently published in The Lancet were spe- cifically for cohort 2, wherein the patients had refractory disease, resistant to prior platinum chemotherapy. Cohort 1, results for whom are not published yet, are cispla- tin-ineligible patients. So, in cohort 2, there

not been any new FDA-approved agent for the management of patients with advanced metastatic urothelial carcinoma. Right now, and following the FDA approval, patients who had progression during or after plat- inum-based chemotherapy administered for metastatic disease or who progressed within 1 year after platinum-based chemo- therapy given for non-adjuvant or adjuvant therapy, can be eligible to receive atezoli- zumab as immunotherapy unless there is a clear, contrary indication. Contraindication, for example, would be active autoimmune disease, patients on immunosuppressive agents for autoimmune disease, so on and so forth; however, the majority of patients are eligible to receive that treatment with- out the need for any biomarker testing. This is what we call for all-comers, meaning all patients could be eligible for that treatment.

was a significant overall response rate with atezolizumab in patients with platinum-pre- treated metastatic urothelial carcinoma, and the response rate appeared to corre- late with expression of the target, the PD-L1 protein in the membrane of immune-infil- trating cells. These results were practice-changing. The FDA recently reviewed the data and granted approval to atezolizumab for patients with advanced urothelial carci- noma pretreated with and resistant to platinum chemotherapy, for patients who received platinum therapy given either for advanced metastatic disease or peo- ple who progressed within 12 months after receiving perioperative platinum-based chemotherapy either in the non-adjuvant or adjuvant setting. Dr. Haffizulla: I see. Now is this the same infor- mation that was presented as one of the ESMO abstracts last year? Dr. Grivas: It’s true. The data were presented initially at ESMO, the European Society of Medical Oncology, meeting in 2015, and the updates were presented recently at the ASCO GU Symposium in 2016 (January 7–9, 2016; San Francisco). The data were published online in The Lancet on March 4, 2016. Dr. Haffizulla: So, how does this change the treatment paradigm? Where does atezoli- zumab now fit in based on these results in this patient subset? Dr. Grivas: This is a very interesting topic because, over the last 30 years, there has

Dr. Haffizulla is the Assistant Dean of Community and Global Health at Nova Southeastern University’s College of Allopathic Medicine. She practices general internal medicine in

Davie, Florida, within her own internal medicine concierge practice. Reference 1. Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum- based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet . 2016;387(10031):1909-1920. www.practiceupdate.com/c/40813

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