• linkedin
  • Increase Font
  • Sharebar

    Combination immunotherapy may raise response rate in mRCC


    “Immune checkpoint inhibitors have revolutionized cancer therapy, but the clinical response rate is still quite low, about 20%, when these agents are used as monotherapy. The data from our study show that combination therapy may offer a much higher response rate with manageable side effects. Thus, it may benefit an even higher proportion of patients with mRCC,” said first author Jianjun Gao, MD, PhD.

    “Longer follow-up in a larger study is needed to determine if the combinations may also improve the durability of responses compared with nivolumab monotherapy,” added Dr. Gao.

    Senior author Padmanee Sharma, MD, PhD, commented on the importance of the studies characterizing the immune and molecular markers. She told Urology Times, “Detailed laboratory studies of tumor samples from patients are needed to understand the molecular and immunologic mechanisms of response and resistance to therapy. This information will be important for guiding our next steps in developing future combination treatment strategies.”

    At the time of data cutoff, the number of available tumor samples was too small to have sufficient power for finding any statistically significant differences in gene expression between treatment arms.

    Nivolumab is approved for treatment of advanced RCC; bevacizumab used with interferon alfa is approved for treatment of mRCC. The rationale for combining ipilimumab with nivolumab is that the two checkpoint inhibitors act on different T cell signaling pathways, the CTLA-4 inhibitory pathway and PD-1 inhibitory pathway, respectively.

    Read - Prostate Ca: Immunotherapy consensus statement published

    “We were also interested in testing this combination because it is approved for treatment of metastatic melanoma based on demonstration of improved anti-tumor T cell responses and clinical responses,” said Dr. Gao.

    “Bevacizumab is an anti-VEGF agent that affects angiogenesis and potentially immune responses, and so we hypothesized that its combination with nivolumab may also lead to enhanced anti-tumor T cell responses.”

    The two nivolumab-based combination regimens are the subject of further investigation. Expansion of the phase I trial with the addition of 45 more patients is planned.

    “We expect the data that are generated will enable development of a larger study investigating nivolumab plus bevacizumab,” said Dr. Sharma.

    Ipilimumab + nivolumab is being compared with sunitinib (Sutent) in a phase III trial of patients with previously untreated advanced RCC or mRCC. Patient accrual is complete in this study sponsored by Bristol-Myers Squibb.

    Dr. Sharma is an unpaid consultant to Bristol-Myers Squibb. The study was funded by the National Institutes of Health and Bristol-Myers Squibb.

    More on Targeted Therapy:

    PCa immunotherapy: Response better when given before ADT

    High-grade bladder Ca: New data improve risk stratification

    RCC: Multiple pathways provide therapeutic targets

    To get weekly news from the leading news source for urologists, subscribe to the Urology Times eNews.


    You must be signed in to leave a comment. Registering is fast and free!

    All comments must follow the ModernMedicine Network community rules and terms of use, and will be moderated. ModernMedicine reserves the right to use the comments we receive, in whole or in part,in any medium. See also the Terms of Use, Privacy Policy and Community FAQ.

    • No comments available