PD-L1 expression as a biomarker for nivolumab (NIVO) plus ipilimumab (IPI) and NIVO alone in advanced melanoma (MEL): A pooled analysis

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PD-L1 expression as a biomarker for nivolumab (NIVO) plus ipilimumab (IPI) and NIVO alone in advanced melanoma (MEL): A pooled analysis

Long GV1, Larkin J2, Ascierto PA3, Hodi FS4, Rutkowski P5, Chiarion Sileni V6, Hassel J7, Lebbe C8, Pavlick A9, Wagstaff J10, Schadendorf D11, Dummer R12, Hogg D13, Haanen J14, Corrie P15, Hoeller C16, Horak C17, Wolchok J18, Robert C19

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.


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