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Long term Survival with CTLA-4 blockade Using Tremelimumab #MMPMID26364516
Eroglu Z; Kim DW; Wang X; Camacho LH; Chmielowski B; Seja E; Villanueva A; Ruchalski K; Glaspy JA; Kim KB; Hwu WJ; Ribas A
Eur J Cancer 2015[Nov]; 51 (17): 2689-97 PMID26364516show ga
Purpose: One of the hallmarks of cancer immunotherapy is the long duration of responses, evident with cytokines like interleukin-2 or a variety of cancer vaccines. However, there is limited information available on very long term outcomes of patients treated with anti-CTLA-4 antibodies. Tremelimumab is an anti-CTLA-4 antibody of Ig G2 istoype initially tested in patients with advanced melanoma over 12 years ago. Methods: We reviewed the outcomes of patients with advanced melanoma enrolled in four phase 1 and 2 tremelimumab trials at two sites to determine response rates and long-term survival. Results: A total of 143 patients were enrolled at two institutions from 2002 to 2008. Tremelimumab administration varied between a single dose of 0.01 mg/kg and 15 mg/kg every 3 months. Median overall survival was 13 months (95% CI, 10?16.6), ranging from less than a month to 12+ years. An objective response rate of 15.6% was observed, with median duration of response of 6.5 years, range of 3 to 136+ months. The Kaplan-Meier estimated 5 year survival rate was 20% (95% CI, 13?26%), with 10 and 12.5 year survival rates of 16% (95% CI, 9?23%). Conclusions: CTLA-4 blockade with tremelimumab can lead to very long duration of objective anti-tumor responses beyond 12 years.