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Management of gastrointestinal (GI) toxicity associated with nivolumab (NIVO) plus ipilimumab (IPI) or IPI alone in phase II and III trials in advanced melanoma (MEL).
Journal article

Management of gastrointestinal (GI) toxicity associated with nivolumab (NIVO) plus ipilimumab (IPI) or IPI alone in phase II and III trials in advanced melanoma (MEL).

  • Weber, Jeffrey S. Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY;
  • Larkin, James M. G. Royal Marsden Hospital, London, United Kingdom;
  • Schadendorf, Dirk University Hospital Essen, Essen, Germany;
  • Wolchok, Jedd D. Memorial Sloan Kettering Cancer Center, New York, NY;
  • Wagstaff, John Singleton Hospital, South West Wales Cancer Institute and Swansea University College of Medicine, Swansea, United Kingdom;
  • Dummer, Reinhard Universitat Zurich, Dermatologische Klinik, Zürich, Switzerland;
  • Hogg, David Princess Margaret Hospital, Toronto, ON, Canada;
  • Guidoboni, Massimo Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy;
  • Sosman, Jeffrey Alan Northwestern University Medical Center, Chicago, IL;
  • Chmielowski, Bartosz University of California Los Angeles, Hematology-Oncology Outpatient Clinic, Los Angeles, CA;
  • Gerritsen, Winald Radboud University Medical Center, Nijmegen, Netherlands;
  • Bhore, Rafia Bristol-Myers Squibb, Princeton, NJ;
  • Walker, Dana Bristol-Myers Squibb, Princeton, NJ;
  • Gonzalez, Rene University of Colorado Comprehensive Cancer Center, Denver, CO;
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Published in:
  • Journal of Clinical Oncology. - American Society of Clinical Oncology (ASCO). - 2017, vol. 35, no. 15_suppl, p. 9523-9523
Cancer Research
Oncology
English 9523 Background: NIVO and IPI are approved as monotherapy and in combination for treatment of MEL. These treatments are associated with select (potentially immune-related) adverse events (AEs) of the GI tract, most commonly diarrhea and colitis. We describe the management of GI toxicity in patients (pts) treated with NIVO+IPI or IPI from phase II (CheckMate 069) and III (CheckMate 067) trials. Methods: Pts received NIVO 1 mg/kg + IPI 3 mg/kg Q3W x 4, followed by NIVO 3 mg/kg Q2W until progression or unacceptable toxicity, or IPI 3 mg/kg Q3W x 4, followed by placebo. Minimum follow-up was 2 yrs for CheckMate 069 and 18 months for CheckMate 067. Results: Of 407 pts treated with NIVO+IPI, 195 (48%) experienced any grade select GI AEs, and of 357 pts treated with IPI, 132 (37%) experienced any grade select GI AEs. Grade 3/4 select GI AEs were reported in 67 (16%) pts treated with NIVO+IPI and in 41 (11%) pts treated with IPI; median time to onset was 7.1 weeks (range 0.9-48.9) with NIVO+IPI and 7.3 weeks (range 0.6-14.9) with IPI. To manage these AEs, immune-modulating medications (IMM) were used in 61/67 (91%) pts in the NIVO+IPI group and in 41/41 (100%) in the IPI group. Corticosteroids (CS) were used in 61/67 (91%) and 41/41 (100%) pts, and infliximab (IFX) was used in 21/67 (31%) and 14/41 (34%) pts in the NIVO+IPI and IPI groups, respectively. In the NIVO+IPI group, the resolution rate of grade 3/4 select GI AEs was 96%, 97%, and 95% with a median time to resolution of 3.3, 3.0, and 3.9 weeks in all treated pts, CS, and CS+IFX managed pts, respectively; 88%, 92%, and 79% resolved with a median time to resolution of 3.9, 2.4, and 7.8 weeks in the IPI group, respectively. Objective response rates (ORR) were unchanged in the presence of any grade select GI AEs, or by using CS or CS+IFX (Table). Conclusions: NIVO+IPI or IPI alone is associated with a high incidence of GI select AEs, but most are effectively managed by IMMs, which do not appear to inhibit tumor response. Clinical trial information: NCT01844505; NCT01927419. [Table: see text]
Language
  • English
Open access status
closed
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Persistent URL
https://sonar.ch/global/documents/22834
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