There are a number of important questions surround the use of immune therapy agents. For instance, how do we assess response to treatment? How long do we treat for? Can we achieve long-term durable response rates? What is the role of radiation therapy (RT) in combination with immune therapy? A very recently published study in Lancet Oncology  reported guidelines for assessing response criteria for use in trials testing immunotherapeutics (iRECIST). In the guidelines, any progressive disease event is considered unconfirmed and requires a confirmatory CT scan at 4-8 weeks. In phase II studies for nivolumab, despite a median OS of 23.4 months (95%CI 17.7-26.9), 29% of patients are alive at 48 months, suggesting that for a subset of patients there is a possibility of durable response and should continue therapy. Two phase II studies are evaluating the role of combination therapy with stereotactic body radiation therapy (SBRT) and immune therapy as a “sensitizing agent.”
Dr. Albiges also discussed strategies for rescuing nivolumab primary/acquired resistance, outlining the TITAN study which will treat all mRCC patients with nivolumab upfront, and for those that have stable or progressive disease, adding additional nivolumab with ipilimumab. Immune therapy is also challenging sunitinib in the first line setting by randomizing patients to nivolumab + ipilimumab vs sunitinib in an ongoing phase III trial (Checkmate214). This also highlights combination therapy utilizing a PD-1 inhibitor (nivolumab) and a CTLA-4 inhibitor (ipilimumab). Furthermore, there are four ongoing trials in the first line setting randomizing various immune therapy agents + VEGF inhibitors vs sunitinib.
In the adjuvant setting, Dr. Albiges notes that we are looking for complete and durable responses, particularly with the favorable safety profile of immune therapy agents. The addition of biomarkers after metastatic lesion biopsy will also assist with targeting/personalizing systemic therapy. The BIONIKK phase II trial is ongoing and designed to determine the molecular subgroup of patient’s metastatic lesions and then appropriately assign nivolumab, ipilimumab or VEGFR TKI. Dr. Albiges concludes that challenges upcoming include delineating the sequence of giving immune therapy agents, targeting specific tumors for appropriate personalized treatment, and building a strong translation program for biomarker research. Novel, exciting trials lie ahead.
1. Seymour L, Bogaerts J, Perrone A, et al. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol 2017;18(3):e143-e152.
Speaker: Laurence Albiges, Institut de Cancerologie Gustave Roussy, Villejuif, France
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto
at the #EAU17 - March 24-28, 2017- London, England