In this abstract, the authors provide an update on the safety and efficacy of durvalamab in patients (pts) with locally advanced/metastatic UC from a multicenter, phase 1/2 open-label study. The original study1 of durvalamab in this population focused on 61 patients, but in this planned update, the number enrolled had increased to 191 patients. All patients had histologically confirmed advanced or metastatic urothelial carcinoma and were ECOG status 0-1. They could be treatment-naïve, have had prior treatment and progressed, or have refused/been ineligible for prior treatments.
Pts received durvalumab 10 mg/kg every 2 weeks (Q2W) for up to 12 months (mo) or until unacceptable toxicity, progression, or starting another anticancer therapy. As this was a phase 1/2 study, the primary endpoints were safety and confirmed objective response rate (ORR) by blinded independent central review according to RECIST criteria. Duration of response (DoR), progression-free survival (PFS) and overall survival (OS) were established secondary endpoints. As with all the other ICI studies, tumor PD-L1 expression was assessed: PD-L1 “high” was defined as = ≥25% PD-L1 expression on tumor or immune cells.
Median follow-up for the cohort was 5.78 months (range 0.4-25.9 month). All patients included had Stage IV disease – locally advanced or metastatic UC (92.7% had visceral metastases, 42.9% had liver metastases, and 7.3% had lymph node only disease). This cohort was primarily made up of patients post-chemotherapy treatment: 99.5% had prior anticancer therapy (95.3% post-platinum). 98 patients were PD-L1 high and 79 were PD-L1 low.
- ORR was 17.8% (34/191), including 7 complete responses
- Responses observed regardless of PD-L1 status
- However, ORR was 27.4% in PD-L1 high patients and 4.1% in PD-L1 low patients
- Responses occurred early (median time to response, 1.41 mo), consistent with other ICI trials.
- Responses were durable (median DoR not reached [NR])
- Median PFS and OS were 1.5 mo (95% CI, 1.4, 1.9) and 18.2 mo (95% CI, 8.1, not estimable [NE]), respectively
- The 1-year OS rate was 55.0% (95% CI, 43.9%, 64.7%)
- Grade 3/4 treatment-related AEs occurred in 6.8% of pts; grade 3/4 immune-mediated AEs occurred in 4 pts; 2 pts discontinued due to immune mediated AEs (acute kidney injury and autoimmune hepatitis). 2 immune mediated treatment related adverse events lead to death.
Limitations / Discussion Points:
1. The percentage of patients with high PD-L1 expression was much higher (>50% of the cohort) than in prior studies. While this is likely due to their specific test, it does present an interesting contrast.
Presented By: Noah M. Hahn
Co-Authors: Thomas Powles, Christophe Massard, Hendrik-Tobias Arkenau, Terence W. Friedlander, Christopher J. Hoimes, Jae-Lyun Lee, Michael Ong, Srikala S. Sridhar, Nicholas J. Vogelzang, Mayer N. Fishman, Jingsong Zhang, Sandy Srinivas, Jigar Parikh, Joyce Antal, Xiaoping Jin, Yong Ben, Ashok Kumar Gupta, Peter H. O'Donnell
Institution(s): Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Barts Cancer Institute, London, United Kingdom; Institut Gustave Roussy Cancer Centre, Villejuif, France; Sarah Cannon Research Institute, University College London Cancer Centre, London, United Kingdom; University of California, San Francisco Medical Center, San Francisco, CA; Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; The Ottawa Hospital Cancer Centre, Ottawa, ON, Canada; Princess Margaret Cancer Centre, Toronto, ON, Canada; Comprehensive Cancer Centers of Nevada, Las Vegas, NV; Moffitt Cancer Center, Tampa, FL; Stanford University, Stanford, CA; Augusta University, Augusta, GA; MedImmune, Gaithersburg, MD; AstraZeneca, Gaithersburg, MD; University of Chicago Comprehensive Cancer Center, Chicago, IL
Written By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Princess Margaret Cancer Centre
at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 – Chicago, Illinois, USA
1. Massard C, Gordon MS, Sharma S, Rafii S, et al. Safety and Efficacy of Durvalumab (MEDI4736), an Anti-Programmed Cell Death Ligand-1 Immune Checkpoint Inhibitor, in Patients With Advanced Urothelial Bladder Cancer. J Clin Oncol. 2016 Sep 10;34(26):3119-25. doi: 10.1200/JCO.2016.67.9761. Epub 2016 Jun 6.