PD-L1 status was not an efficacy biomarker for nivolumab. Among patients with PD-L1 expression ≥1%, median OS was 21.8 months with nivolumab versus 18.8 months with everolimus. In patients with PD-L1 expression ≤1%, median OS was 27.4 and 21.2 months in the two arms, respectively. Similar outcomes were observed when using a 5% threshold for PD-L1 expression status, although only a small number of patients were evaluable by this criterion.
“The finding that overall survival was higher among patients treated with nivolumab, irrespective of PD-L1 expression, suggests that PD-L1 expression should not be used to determine which patients might respond to the therapy and whether or not offer it to them,” said Sharma.
“PD-L1 is a dynamic biomarker that changes over time as a result of evolving immune responses. So it is not surprising that PD-L1 measured in tumor samples before treatment does not capture the true expression of PD-L1 and how it may correlate to responses to treatment. I would expect that tumour samples taken while patients were on-treatment, as opposed to pretreatment, might indicate that PD-L1 expression, as well as other markers of immune response, has a correlation with response to treatment,” Sharma added.
Nivolumab was initially approved in December 2014 for patients with unresectable or metastatic melanoma following treatment with ipilimumab (Yervoy) or a BRAF inhibitor. In March 2015, the PD-1 inhibitor was approved for the treatment of patients with advanced squamous non–small cell lung cancer (NSCLC) who have progressed on or after platinum-based chemotherapy.
The FDA is currently reviewing applications for frontline nivolumab as a monotherapy and in combination with ipilimumab for patients with advanced melanoma, as well as for an indication for patients with previously treated nonsquamous NSCLC.
Sharma P, Escudier B, McDermott DF, et al. CheckMate 025: a randomised, open-label, phase III study of nivolumab (NIVO) versus everolimus (EVE) in advanced renal cell carcinoma (RCC). Presented at: 2015 European Cancer Congress; September 25-29; Vienna, Austria. Abstract LBA 3.
Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma [published online September 25, 2015]. N Engl J Med. doi:10.1056/NEJMoa1510665.
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