Poster Presentation Joint 2016 COSA and ANZBCTG Annual Scientific Meeting

PD-L1 expression as a biomarker for nivolumab (NIVO) plus ipilimumab (IPI) and NIVO alone in advanced melanoma (MEL): A pooled analysis (#240)

Georgina Long 1 , James Larkin 2 , Paolo Ascierto 3 , Stephen Hodi 4 , Piotr Rutkowski 5 , Vanna Chiarion-Selini 6 , Jessica Hassel 7 , Celeste Lebbe 8 , Anna Pavlick 9 , John Wagstaff 10 , Dirk Schadendorf 11 , Reinhard Dummer 12 , David Hogg 13 , John Haanen 14 , Pippa Corrie 15 , Christopher Hoeller 16 , Christine Horak 17 , Jedd Wolchok 18 , Caroline Robert 19 20
  1. Melanoma Institute Australia, University of Sydney and Royal North Shore and Mater Hospitals, Sydney, NSW, Australia
  2. Royal Marsden Hospital, London, United Kingdom
  3. Istituto Nazionale Tumori Fondazione Pascale , Naples, Italy
  4. Dana-Farber Cancer Institute, Boston, MA, USA
  5. Centrum Onkologii - Instytut Im. Marii Sklodowskiej-Curie, Warsaw, Poland
  6. Instituto Oncologico , Veneto, Padova, Italy
  7. Department of Dermatology, University Hospital Heidelberg, Heidelberg, Germany
  8. Hôpital Saint-Louis, Paris, France
  9. New York University, New York, NY , USA
  10. South West Wales Cancer Institute and Swansea University College of Medicine, Swansea, Wales
  11. Department of Dermatology, University of Essen, Essen, Germany
  12. Universitäts Spital, Zurich, Switzerland
  13. Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada
  14. The Netherlands Cancer Institute, Amsterdam, Netherlands
  15. Addenbrooke's Hospital, Cambridge, UK
  16. Department of Dermatology, Medical University of Vienna, Vienna, Austria
  17. Bristol-Myers Squibb, Princeton, NJ, USA
  18. Memorial Sloan-Kettering Cancer Centre, New York, NY, USA
  19. Cancer Institute Gustave Roussy, Villejuif, France
  20. Paris-Sud University, Villejuif-Paris-Sud, France

Aims: NIVO+IPI and NIVO have superior clinical activity vs IPI in MEL patients, irrespective of PD-L1 tumor expression. We describe PD-L1 as a biomarker for NIVO+IPI and NIVO efficacy across phase 2 (CheckMate 069) and phase 3 (CheckMate 066/067) trials.

Methods: Patients (N=832) 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 was assessed for PD-L1 expression using Dako immunohistochemistry. Minimum follow-up was 18 months.

Results: Among patients with PD-L1 expression ≥5%, median progression-free survival (mPFS) of NIVO+IPI was not reached (NR) and was 22.0 months for NIVO alone (hazard ratio [HR]: 0.99, 95% CI: 0.66-1.46). For patients with low to no PD-L1 (<5%), mPFS was 11.1 months for NIVO+IPI and 4.9 months for NIVO (HR: 0.70, 95% CI: 0.57-0.87). Objective response rate (ORR) was higher with NIVO+IPI vs NIVO in patients 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 months in NIVO ≥5% and <5% PD-L1 subgroups, respectively. 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 patients with ≥5% PD-L1 tumor expression have better efficacy outcomes, those with <5% PD-L1 expression still benefit from NIVO+IPI or NIVO. Among patients with high PD-L1 expression, mPFS of NIVO+IPI and NIVO was similar, but the ORR of NIVO+IPI was numerically higher across PD-L1 subgroups. As survival data have not yet matured, caution is advised when applying these results to assess the relative benefit of NIVO+IPI vs NIVO.