2019 ASCO Annual Meeting!
Session: Melanoma/Skin Cancers
Type: Oral Abstract Session
Time: Tuesday June 4, 9:45 AM to 12:45 PM
Efficacy and safety of the combination of nivolumab (NIVO) plus ipilimumab (IPI) in patients with symptomatic melanoma brain metastases (CheckMate 204).
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr 9501)
Author(s): Hussein Abdul-Hassan Tawbi, Peter A. J. Forsyth, F. Stephen Hodi, Christopher D. Lao, Stergios J. Moschos, Omid Hamid, Michael B. Atkins, Karl D. Lewis, Reena Parada Thomas, John A. Glaspy, Sekwon Jang, Alain Patrick Algazi, Nikhil I. Khushalani, Michael A. Postow, Anna C. Pavlick, Marc S. Ernstoff, David A. Reardon, Agnes Balogh, Jasmine I. Rizzo, Kim Allyson Margolin; The University of Texas MD Anderson Cancer Center, Houston, TX; H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Dana-Farber Cancer Institute, Boston, MA; University of Michigan, Ann Arbor, MI; University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; The Angeles Clinic and Research Institute, Los Angeles, CA; Georgetown Lombardi Comprehensive Cancer Center, Washington, DC; University of Colorado Comprehensive Cancer Center, Aurora, CO; Stanford University Hospital, Palo Alto, CA; Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA; Inova Schar Cancer Institute, Virginia Commonwealth University, Fairfax, VA; University of California, San Francisco, San Francisco, CA; Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY; Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY; Roswell Park Comprehensive Cancer Center, Buffalo, NY; Bristol-Myers Squibb, Princeton, NJ; City of Hope, Duarte, CA
Background: We previously reported efficacy and safety of NIVO+IPI in patients (pts) with untreated, asymptomatic, melanoma brain metastases (MBM) from the CheckMate 204 study. Here, we provide the first report of NIVO+IPI in pts with symptomatic MBM, and report updated data in pts with asymptomatic MBM. Methods: In this phase II trial, pts with ≥1 measurable, nonirradiated MBM 0.5–3.0 cm were enrolled into two cohorts: (1) those with no neurologic symptoms or steroid Rx (asymptomatic; cohort A); and (2) those with neurologic symptoms, whether or not they were receiving steroid Rx (symptomatic; cohort B). In both cohorts, pts received NIVO 1 mg/kg + IPI 3 mg/kg Q3W × 4, then NIVO 3 mg/kg Q2W until progression or toxicity. The primary endpoint was intracranial clinical benefit rate (CBR; proportion of pts with complete response [CR] + partial response [PR] + stable disease [SD] ≥6 mo). As of the clinical cutoff date on May 1, 2018, all treated pts (101 in cohort A and 18 in cohort B) had been followed for ~6 mo or longer. Results: In this updated analysis of cohort A (median follow-up of 20.6 mo), the CBR was 58.4% (Table). In cohort B, pts received a median of 1 NIVO+IPI dose and 2 of 18 pts (11%) received all 4 doses. At a median follow-up of 5.2 months in cohort B, intracranial objective response rate was 16.7% and the CBR was 22.2%. Grade 3/4 adverse events occurred in 54.5% of pts in cohort A and in 55.6% of pts in cohort B (6.9% and 16.7% in the nervous system, respectively), with one death related to treatment in cohort A (immune-related myocarditis). Conclusions: In pts with asymptomatic MBM, our updated results show a high rate of durable intracranial responses, further supporting NIVO+IPI as a first-line treatment in this population. Intracranial antitumor activity was observed with NIVO+IPI in pts with symptomatic MBM, but further study is needed to understand the biologic mechanisms of resistance to immunotherapy and to improve treatments in this challenging population. Clinical trial information: NCT02320058
(Cohort A; n = 101)
(Cohort B; n = 18)
|Best overall response, n (%)|
|CR||29 (29)||2 (11)|
|PR||26 (26)||1 (5.6)|
|SD ≥6 mo||4 (4)||1 (5.6)|
|CBR, % (95% CI)||58.4 (48.2–68.1)||22.2 (6.4–47.6)|