1Melanoma Institute Australia, The University of Sydney, and Royal North Shore and Mater Hospitals, Australia; 2Royal Marsden Hospital, UK; 3Istituto Nazionale Tumori Fondazione Italy; 4Dana-Farber Cancer Institute, MA, USA; 5Maria Sklodowska-Curie Memorial Cancer Center, Poland; 6Istituto Oncologico Veneto, Italy; 7University Hospital Heidelberg, Germany; 8Hôpital Saint-Louis, France; 9New York University, USA; 10South West Wales Cancer Institute and Swansea University College of Medicine, Wales; 11University Hospital Essen, Germany; 12Universitaets Spital, Zurich, Switzerland; 13Princess Margaret Cancer Centre, ON, Canada; 14The Netherlands Cancer Institute, Amsterdam; 15Addenbrooke’s Hospital, UK; 16Medical University of Vienna, Austria; 17Bristol-Myers Squibb, USA; 18Ludwig Center at Memorial Sloan Kettering Cancer Center, USA; 19Gustave Roussy and Paris-Sud University, Villejuif Paris-Sud, France
Background: NIVO+IPI and NIVO showed superior clinical activity vs IPI in a phase 3 trial of MEL patients (pts), irrespective of PD-L1 tumor expression. Among pts with high PD-L1 expression (≥5%), median progression-free survival (mPFS) was similar between NIVO+IPI and NIVO, but overall response rate (ORR) was higher with NIVO+IPI. We describe PD-L1 as a biomarker for NIVO+IPI and NIVO efficacy across phase 2 (CheckMate 069) and phase 3 (CheckMate 066 and 067) trials. Methods: Treatment-naïve pts (N=832) with MEL received NIVO 1 mg/kg + IPI 3 mg/kg Q3W × 4 or NIVO 3 mg/kg Q2W, followed by NIVO 3 mg/kg Q2W until progression or unacceptable toxicity. Tumor tissue from primary or metastatic sites, obtained at screening, was assessed for PD-L1 expression using a validated Dako immunohistochemistry assay. Minimum pt follow-up was 18 months (mos). Survival data remain immature. Results: The proportion of pts with PD-L1 expression ≥5% was 26% (92/358) for NIVO+IPI and 29% (139/474) for NIVO. Pt characteristics were similar between PD-L1 subgroups, although fewer pts had LDH>ULN in the PD-L1 ≥5% subgroup. Among pts with PD-L1 expression ≥5%, mPFS of NIVO+IPI was not reached (NR) and was 22.0 mos for NIVO alone (hazard ratio [HR]: 0.99, 95% CI: 0.66─1.46). For pts with low to no PD-L1 (<5%), mPFS was 11.1 mos for NIVO+IPI and 4.9 mos for NIVO (HR: 0.70, 95% CI: 0.57─0.87). ORR was higher with NIVO+IPI vs NIVO in pts with ≥5% (68.5% vs 59.0%) and <5% (54.9% vs 39.7%) PD-L1 expression. Median duration of response was NR in both PD-L1 subgroups for NIVO+IPI, and 20.8 and 22.3 mos in NIVO ≥5% and <5% PD-L1 subgroups, respectively. The frequency and types of treatment-related grade 3-4 adverse events were consistent with earlier reports (NIVO+IPI: 56.5%, NIVO: 18.2%) and did not differ by PD-L1 expression.
Conclusions: While pts with ≥5% PD-L1 tumor expression have better efficacy outcomes, those with <5% PD-L1 expression still benefit from NIVO+IPI or NIVO. Among pts with high PD-L1, mPFS of NIVO+IPI and NIVO were similar, but the ORR of NIVO+IPI was numerically higher across PD-L1 subgroups. As OS data have not yet matured, caution is advised when applying these results to assess the relative benefit of NIVO+IPI vs NIVO.
Acknowledgements: This study was funded by Bristol-Myers Squibb. Professional medical writing and editorial assistance were provided by Stephan Lindsey, PhD, and Cara Hunsberger at StemScientific, funded by Bristol-Myers Squibb.
Originally presented at the European Society for Medical Oncology Congress, 7-11 October 2016, Copenhagen, Denmark. Abstract: 3381.
Credits: None available.
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