Nivolumab shown to be effective in patients with non-clear cell RCC

By Liz Meszaros, MDLinx
Published December 13, 2017

Key Takeaways

In patients with non-clear cell renal cell carcinoma (non-ccRCC), nivolumab monotherapy provided substantial anti-tumor effects, and was relatively well tolerated by patients, according to research presented at the Sixteenth International Kidney Cancer Symposium, in Miami, FL.

Non-ccRCC represents a heterogeneous group of tumors that account for 15% to 20% of all renal malignancies, but studies in these patients are few.

“The most common histology in renal cell carcinoma is clear-cell histology, and most of the trial data are based on those patients,” began lead researcher Vadim S. Koshkin, MD, hematology/oncology fellow, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH. “And most of the treatment patterns in non-ccRCC patients are extrapolated from data that is generated in clear-cell patients. However, the biology of these histologies is really quite different, and certainly, there’s evidence that certain treatments do not work as well."

Nivolumab is approved for the treatment of mRCC, but has only been studied in patients with clear cell histology. Dr. Koshkin and colleagues, therefore, conducted this study to assess the clinical activity of nivolumab in patients with non-ccRCC.

For their retrospective analysis, they included 41 mRCC patients (mean age: 58 years; 71% male; 68% Caucasian) with a non-clear cell histology treated with nivolumab between December 2015 and June 2017, from six institutions: the Cleveland Clinic, Duke, Georgetown, Comprehensive Cancer Centers of Nevada, City of Hope, and the University of Pittsburgh Medical Center.

All patients had histologically-confirmed non-ccRCC with measurable metastases and had received at least one dose of nivolumab administered as monotherapy. To be eligible for response assessment, patients must have had at least one imaging assessment or clinical progression as assessed by the treating physician following initiation of nivolumab therapy.

Most patients had ECOG PS 1 (47%), followed by ECOG PS 0 (40%). Histology was papillary in 39%, followed by unclassified in 34%, chromophobe in 12%, collecting duct in 10%, translocation in 2%, and mucinous tubular and spindle cell carcinoma (MTSCC) in 2%.

Patients were followed for a mean of 8.5 months, the median duration of nivolumab was 3 months, and the median number of doses was seven.

According to classification via MSKCC Criteria, 64% of patients were at intermediate risk, and 62% were at intermediate risk according to IMDC Criteria. Seventy-three percent of patients had undergone previous nephrectomy, and most (62%) had had one prior systemic therapy.

Dr. Koshkin and colleagues evaluated 35 patients for best response to nivolumab—via RECIST v1.1 criteria—and found an objective response rate (ORR) of 20%, a complete response (CR) of 0%, partial response (PR) of 20%, stable disease (SD) in 29%, and progressive disease (PD) in 51%.

When they grouped the best response by histology subtype, Dr. Koshkin and colleagues found that patients with an unclassified history had the highest PR rate (36%), followed by those with collecting duct histology (25%), and those with papillary histology (14%).

PD was seen in 100% of patients with translocation histology, and in 64% of those with papillary histology.
Treatment related adverse events (TRAEs) occurred in 37% of patients, and lead to treatment discontinuation in 34%, hospitalization in 12%. No deaths occurred due to TREAEs.

In all, 81% of patients discontinued nivolumab due to disease progression, while 19% discontinued due to treatment intolerance.

“Based on our results, the objective response rates and progression-free survival were comparable in this non-ccRCC population to previously reported numbers in clear-cell patients. Many of the responses were durable as well. Additionally, nivolumab was fairly well tolerated,” said Dr. Koshkin.

“In non-ccRCC patients, nivolumab is a treatment option in the second-line setting,” he concluded.

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