San Diego, CA USA (UroToday.com) In this session, Dr. Harshman spoke about emerging neoadjuvant approaches to perioperative immunotherapy. In 2016, the systemic treatment armamentarium for metastatic renal cell carcinoma (mRCC) consists of 3 classes: mTor inhibitors, VEGF-targeted agents, and immunotherapy (IL-2, interferon alpha, nivolumab).
Although results from EVEREST and others are eagerly anticipated, there has been no major success using adjuvant therapies in kidney cancer to date. Therefore, Dr. Harchman argued for the next step to be moving therapy forward is in the disease process.
In the mRCC population, nivolumab demonstrated improved overall survival of 25 months versus 19.6 months compared to standard therapy (HR 0.73, p = 0.0018). Based on the results of this trial, nivolmab has been approved in the VEGF refractory mRCC space.
The argument to move PD-1 blockade earlier in the disease process is three-fold. (1) the durability of response can be long lasting; (2) continued response or disease stabilization occurs even off therapy (so-called “memory response”); and (3) the overall tolerability as monotherapy is high making it a good potential partner compound with other agents.
The question still remains, however, what the best treatment design would be. Namely, is it neoadjuvant, adjuvant (unlikely), or the “trifecta” of neoadjuvant-adjuvant surgical sandwich? A neoadjuvant approach brings about questions of duration and sufficient dosing for efficacy in addition to concerns about prolonged delays to curative resection. Further, the likelihood of needing combination therapy is high since monotherapy is rarely sufficient. Finally issues around which patients to select – high risk stages, PD-L1 positive only, inflammatory tumors, and mutation/immune/cytokine signatures – about making optimal trial design difficult.
Despite these challenges, there remains a strong rationale for presurgical priming. A group at Johns Hopkins University is exploring the safety and feasibility of 3 doses of neoadjuvant nivolumab followed by radical versus partial nephrectomy. The ECOG group is introducing EA81143. All patients in the study receive a renal mass biopsy. Patients are then randomized to surgery upfront followed by observation versus neoadjuvant nivolumab (2 doses) followed by surgery followed by 9 months of adjuvant therapy. The primary outcome measure is clear cell renal cell carcinoma recurrence-free survival. The secondary endpoint is overall survival. Other outcome measures are safety, tolerability, and quality of life.
Dr. Harshman closed with imploring the audience to accept the so-called “trifecta” of presurgical priming with PD-1 blockade, surgery, and adjuvant therapy. She again reiterated earlier remarks about a complex, dynamic interplay between the tumor and the immune system. Overall, there is great hope and promise for improving care in patients with advanced renal cell carcinoma using new immunotherapeutic approaches.
Presented By: Lauren Harshman, MD
Reported By: Benjamin T. Ristau, MD, Fox Chase Cancer Center, Philadelphia, PA. at the 2016 AUA Annual Meeting - May 6 - 10, 2016 – San Diego, California, USA
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