4:14 PM
Mar 13, 2018
 |  BC Extra  |  Preclinical News

Benefit of PD-1/PD-L1 treatment lasts beyond discontinuation

New research from the Dana-Farber Cancer Institute suggests that blocking the PD-1 pathway could lead to a sustained clinical benefit in patients, potentially making continuous dosing of PD-1 or PD-L1 inhibitors to treat cancer unnecessary.

Current standard of care for renal cell carcinoma (RCC) patients is to administer PD-1/PD-L1 inhibitors on a continuous basis until disease progression or development of toxicities.

In the paper, published in Cancer Immunology Research, the authors analyzed clinical outcomes of 19 patients with metastatic RCC who experienced an initial clinical response to an anti-PD-1 or PD-L1 mAb, but had to discontinue treatment due to an immune related adverse event. The researchers found that 13 patients (68.4%) maintained a clinical benefit for at least 6 months after treatment was discontinued, as measured by time to progression after date of treatment cessation.

The authors suggest that this data supports the "memory" component of the adaptive immune response to PD-1 blockade, in which activated tumor-responsive effector T cells transition to memory T cells, leading to a persistent clinical benefit of checkpoint inhibitors even after treatment discontinuation.

In the paper, the authors highlight the need for biomarkers that can predict a patient's durability of response to checkpoint inhibitors. The authors also suggest that continuous dosing of PD-1 or PD-L1 inhibitors should be investigated in clinical trials to further understand the length of their effect on tumors, as well as immunological memory.

Dana-Farber and Bristol-Myers Squibb Co. (NYSE:BMY) are evaluating the impact of Opdivo nivolumab and Yervoy ipilimumab discontinuation in a Phase II trial in patients with advanced RCC who cease treatment after a confirmed response.

In December, FDA granted Priority Review to a combination of Opdivo plus Yervoy to treat intermediate- and poor-risk patients with advanced RCC. The PDUFA date is April 16, 2018 (see BioCentury Extra, Dec. 14, 2017).

Opdivo is a human IgG4 mAb against PD-1. Yervoy is a human mAb against CTLA-4. FDA previously approved the combination to treat metastatic melanoma.

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