Optimal Targeting of the PD-1/PDL-1 Pathway in Metastatic Renal Cancer

摘要

Recent clinical trials of monoclonal antibodies that target the PD- 1/PDL-1 pathway in renal cancer have demonstrated promising clinical efficacy with benefit persisting off therapy in a subset of patients. In a phase I trial of the anti-PD-1 blocking antibody nivolumab (Bristol-Myers Squibb), 10 out of 34 patients with renal cancer experienced major tumor responses, and nine others had stable disease lasting at least 24 weeks. In the 16 patients treated at the lOmg/kg dose level, almost 70% were progression-free at 6 months, and four patients have yet to progress despite being off therapy for more than 16 weeks (Fig. 1). Another anti-PD-1 antibody, lambrolizumab (Merck and Co., Inc.), showed similar efficacy to nivolumab in patients with melanoma and patients with lung cancer, and is now being studied in other cancers, including renal.5 In this phase I study reported by Cho et al., the PDL-1 antibody MPDL3280A (Genentech) was administered to 53 patients with metastatic renal cancer resulting in a 13% incidence of drug-related grade 3/4 adverse event, a response rate of 13%, and 50% of patients progression-free at 6 months. Although the early results seen with PD-1/PDL-1-blocking antibodies in solid tumors, including renal cancer, have been encouraging, more work is needed to optimize the use of PD-1-based immunotherapy.