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Programmed death-1 blockade in mismatch repair deficient colorectal cancer.

2016; Lippincott Williams & Wilkins; Volume: 34; Issue: 15_suppl Linguagem: Inglês

10.1200/jco.2016.34.15_suppl.103

1527-7755

Dung T. Le, Jennifer N. Uram, Hao Wang, Bjarne R. Bartlett, Holly Kemberling, Aleksandra Eyring, Nilofer S. Azad, Dan Laheru, Ross C. Donehower, Todd S. Crocenzi, Richard M. Goldberg, George A. Fisher, James J. Lee, Tim F. Greten, Minori Koshiji, Soonmo Peter Kang, Robert A. Anders, James R. Eshleman, Bert Vogelstein, Luis A. Díaz,

Colorectal Cancer Treatments and Studies

103 Background: Mismatch repair deficient (dMMR) colon cancers are densely infiltrated with CD8+T cells and regress when treated with anti-programmed death-1 (PD-1) antibodies. This anti-tumor response is thought to be potentiated by the thousands of somatic mutations that when expressed as proteins result in hundreds of potentially immunogenic neo-antigens that can be recognized by the patient's immune system. Methods: We previously reported a phase 2 study to evaluate the activity of pembrolizumab (pembro), a PD-1 antibody in treatment refractory dMMR colon cancers (NEJM 2015). We are reporting the expanded trial and updated data for the mismatch repair deficient CRC (dMMR, cohort A) and mismatch repair proficient CRC (pMMR, cohort B) cohorts. Pembro was administered at 10 mg/kg every 14 days in patients with 2 or more prior therapies. The co-primary endpoints were response and progression-free survival rate at 20 weeks. Secondary endpoints included disease control rate (DCR = CR + PR + SD), progression free survival (PFS), overall survival (OS) and safety. Results: A total of 53 patients (Cohort A: n = 28, Cohort B: n = 25) were treated. Median follow up time is 8.7 months. RR and DCR were 50% (14/28, 95% confidence interval (CI): 31-69%) and 89% (25/28) for dMMR CRC and 0% (0/25, 95% CI: 0-14%) and 16% (4/25) for pMMR CRC, respectively. Twenty-one of 28 dMMR CRC patients remain on study. Median PFS was not reached (NR) for dMMR CRC and 2.4 months for pMMR CRC (HR = 0.135; 95% CI 0.043 to 0.191; p=<0.0001). Median OS was NR for dMMR vs. 6 months for pMMR (HR = 0.247; 95% CI 0.117 to 0.589; p=0.001). For dMMR CRC, the PFS rates was 61% at 24 months and the OS rate was 66% at 24 months. Among patients with an objective response (n=14), only 1 has developed secondary resistance to pembro with a solitary brain metastasis after 4.6 months of therapy. Conclusions: Patients with dMMR CRC receive durable clinical benefit with pembrolizumab. Clinical trial information: NCT01876511.