Poster Presentation Joint 2016 COSA and ANZBCTG Annual Scientific Meeting

Safety profile of nivolumab (NIVO) and ipilimumab (IPI) combination therapy in patients with advanced melanoma (MEL) (#216)

Mario Sznol 1 , Pier Ferrucci 2 , David Hogg 3 , Michael Atkins 4 , Pascal Wolter 5 , Massimo Guidoboni 6 , Celeste Lebbe 7 , John Kirkwood 8 , Jacob Schachter 9 , Gregory Daniels 10 , Jessica Hassel 11 , Jonathan Cebon 12 , Winald Gerritsen 13 , Victoria Atkinson 14 , Luc Thomas 15 , John Mccaffrey 16 , Derek Power 17 , Joel Jiang 18 , Stephen Hodi 19 , Jedd Wolchok 20
  1. Yale Cancer Center, New Haven, CT, USA
  2. Istituto Europeo Di Oncologia, Milan, Italy
  3. Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada
  4. Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC, USA
  5. Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium
  6. Immunotherapy and Somatic Cell Therapy Unit, IRCCS IRST , Meldola, Italy
  7. Hôpital Saint-Louis, Paris, France
  8. Hillman Cancer Center, Pittsburgh, PA, USA
  9. Ella Lemelbaum Institute of Melanoma, Sheba Medical Center , Ramat Gan, Israel
  10. University of California, San Diego, Moores Cancer Center, La Jolla, CA, USA
  11. Department of Dermatology, University Hospital Heidelberg, Heidelberg, Germany
  12. Cancer Immunobiology, Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia
  13. Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands
  14. Gallipoli Medical Research Foundation and Princess Alexandra Hospital, Woolloongabba, QLD, Australia
  15. Department of Dermatology, Centre Hospitalier Lyon Sud, Pierre-Bénite Cedex, France
  16. Irish Clinical Oncology Research Group, Dublin, Ireland
  17. Irish Clinical Onoclogy Reserach Group, Cork, Ireland
  18. Bristol-Myers Squibb, Princeton, NJ, USA
  19. Dana-Farber Cancer Institute, Boston, MA, USA
  20. Memorial Sloan-Kettering Cancer Centre, New York, NY, USA

Aims: Cumulative data indicate greater tumor response from the combination of NIVO+IPI in patients with MEL, but with higher frequency of adverse events (AEs) compared with either agent alone. This pooled analysis of 3 studies describes the safety profile of NIVO+IPI utilizing established guidelines for AE management.

Methods: A retrospective safety review was conducted for phase 1–3 trials in which patients received ≥1 dose of the standard regimen, NIVO 1 mg/kg + IPI 3 mg/kg Q3W x 4, then NIVO 3 mg/kg Q2W until progression or unacceptable toxicity. Analyses included AEs, select (immune-related) AEs, time to onset and resolution, use of immune-modulating agents (IMs) for toxicity management, and effect of IMs on outcome.

Results: Among 448 patients, median age was 61 years, and 25% had ECOG PS >0. Median duration of follow-up was 13.2 months. Treatment-related grade 3/4 AEs occurred in 55% of patients and led to discontinuation in 28%. The most frequent treatment-related select AEs of any grade were skin (64%) and gastrointestinal (47%), and of grade 3/4 were hepatic (17%) and gastrointestinal (16%); 30% developed a grade 2–4 select AE in >1 organ category. Median time to onset of grade 3/4 select AEs ranged from 3.1 (skin) to 16.3 weeks (renal). Excluding endocrine AEs, median time to resolution and resolution rates of grade 3/4 select AEs were 1.1 (renal) to 7.3 weeks (pulmonary) and 79–100%, respectively, using IMs. Four (<1%) deaths were attributed to therapy.

Conclusions: The frequency of grade 3/4 treatment-related AEs was higher with NIVO+IPI, and time to onset of select AEs occurred earlier than with either agent alone. Resolution rates of select AEs were similar to those previously reported with IPI monotherapy.