Preoperative immune checkpoint inhibitor (ICI) therapy is associated with high response rates in patients with metastatic renal cell carcinoma (RCC), according to results presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

While surgical options such as cytoreductive nephrectomy and/or metastasectomy are considered to play an important role in the treatment of patients with metastatic RCC, the role of ICI-based neoadjuvant therapy has not previously been explored in this setting.

In this randomized, open-label phase 1 study ( Identifier: NCT02210117), 104 patients with biopsy-confirmed metastatic RCC and measurable disease who were eligible for cytoreductive nephrectomy, metastasectomy, or posttreatment biopsy were randomly assigned in a 2:3:2 ratio to receive preoperative therapy with nivolumab alone (N; every 2 weeks for 3 cycles) or in combination with either bevacizumab (N + B; every 2 weeks for 3 cycles) or ipilimumab (N + I; every 3 weeks for 2 cycles) followed by cytoreductive surgery or posttreatment biopsy and then maintenance nivolumab for 2 years.

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The primary end point of the study was safety, with secondary outcome measures including immunological changes in tumor and examination of peripheral blood to assess for potential biomarkers of clinical response and resistance to therapy, best overall response (BOR; ie, optimal response of overall response followed by surgery as assessed at 12 weeks), progression-free survival (PFS), and overall survival (OS).

Importantly, however, the study presenter Jianjun Gao, MD, PhD, department of genitourinary medical oncology, University of Texas MD Anderson Cancer Center, Houston, noted that “this trial was not designed to compare clinical outcomes between arms. Instead, it was designed as a biomarker study.”

Regarding safety for the overall group, the respective rates of grade 3 or higher adverse events were 28%, 38% (including 18% of these patients experiencing grade 3 or higher hypertension), and 43% for those receiving N, N + B, and N + I.

Overall rates of BOR were 59%, 44%, and 43% for those receiving N, N + B, and N + I. For those patients who underwent cytoreductive surgery (44 individuals), BOR rates were 86% (N), 82% (N + B), and 69% (N + I), with surgical resection of target lesions in 4 (N), 4 (N + B), and 3 (N + I) patients contributing to these increased rates. Respective BOR rates for those patients not undergoing surgery (59 individuals) were 33% (N), 21% (N + B), and 24% (N + I).

At a median follow-up of more than 2 years, median OS has not been reached in the surgical group, with a 2-year OS rate of 84%. In contrast, median OS was 19.6 months in the nonsurgical group, with a 2-year OS rate of 46%.

Laboratory correlates of clinical response included interferon-related gene expression in pretreatment tumor tissues, as well as the level of tumor infiltrating CD8 T-cells in pre- and posttreatment tumor specimens.

In his concluding remarks, Dr Gao stated that their “data suggest that immune checkpoint therapy plus cytoreductive therapy improved clinical outcomes for patients with metastatic RCC, and this strategy should be tested in a larger randomized clinical trial.”


Gao J, Karam JA, Tannir NM, et al. A pilot randomized study evaluating nivolumab (nivo) or nivo + bevacizumab (bev) or nivo + ipilimumab (ipi) in patients with metastatic renal cell carcinoma (MRCC) eligible for cytoreductive nephrectomy, metastasectomy or post-treatment biopsy (Bx). Presented at: 2019 American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 4501.

This article originally appeared on Cancer Therapy Advisor