Washington, DC (UroToday.com): Dr. Hans Hammers presented today about the changing landscape in treatment of metastatic Renal Cell Carcinoma with immunotherapy.
PD1/PDL1 pathway and CTLA4 inhibitors are both explored for immunotherapy. PD1, expressed in T cells, inhibits anti-tumor immune response via interaction with PDL1, as expressed on tumor cells. CTLA4 inhibitors also negatively regulate immune response.
Dr. Hammers shows a case study of patient who was a poor-risk per MSKCC criteria and progressed after receiving sunitinib, temsirolimus, sorafenib, and pazopanib. The patient was placed on Nivolumab, PD1 antibody, and disease responded and the patient is still alive 5 years later.
Dr. Hammers than reviewed the recent CheckMate 025, which led to FDA approval for Nivolumab in metastatic RCC patients. The study randomized previously treated metastatic RCC patients to Nivolumab versus Everolimus and assessed for progression-free survival, overall survival, and side-effect profile. 72% of patients received 1 VEGF therapy and 28% received 2 VEGF therapies.
Median progression free survival was no different between both regimens. However, the tail end of the PFS curve seems to show a separation. This illustrates that a proportion of patient may have a durable response. Overall Survival was significant favoring Nivolumab (HR 0.73 [0.57-0.93, p = 0.0018). All subgroups favored Nivolumab with respect to overall survival. There was a marginal survival response in age > 75 which Dr. Hammers believes is not necessarily true clinically as he sees several patients in that age group in his clinic who clearly benefits.
PDL1 expression on the tumor specimen did not predict overall survival. Objective response rate was 25% in Nivolumab versus 5% in Everolimus. The safety profile showed 19% treatment related Grade 3/4 adverse side-effect on Nivolumab compared to 37% on Everolimus. Most patients tolerated the treatment well. Most common side-effect include fatigue and nausea. A clinically meaningful QoL was seen favoring Nivolumab.
Dr. Hammers then discussed other phase I trials using combinations of checkpoint inhibitors as well as combinations of VEGF pathway with PD1/PDL1 pathways. Response rate with combination checkpoint inhibitors (Nivolumab/Iplimumab) is excellent. However, adverse effects are also increased. The main adverse events include hepatitis and colitis.
Ongoing Phase III trials that may transform 1st therapy are planned. These include Nivolumab/Iplimumab versus Sunitinib, Atezolizumab/Bev vs Sunitinib, Avelumab/Axitinib vs Sunitinib.
In conclusion, current landscape in treating metastatic RCC is changing with immunotherapy.
Hans J Hammers, MD
Johns Hopkins University
Mohammed Haseebuddin, MD from the Society of Urologic Oncology Meeting - December 2 - 4, 2015 – Washington, DC.
Fox Chase Cancer Center, Philadelphia, PA.