TY - JOUR
T1 - Durable cancer regression off-treatment and effective reinduction therapy with an anti-PD-1 antibody
AU - Lipson, Evan J.
AU - Sharfman, William H.
AU - Drake, Charles G.
AU - Wollner, Ira
AU - Taube, Janis M.
AU - Anders, Robert A.
AU - Xu, Haiying
AU - Yao, Sheng
AU - Pons, Alice
AU - Chen, Lieping
AU - Pardoll, Drew M.
AU - Brahmer, Julie R.
AU - Topalian, Suzanne L.
PY - 2013/1/15
Y1 - 2013/1/15
N2 - Purpose: Results from the first-in-human phase I trial of the anti-programmed death-1 (PD-1) antibody BMS-936558 in patients with treatment-refractory solid tumors, including safety, tolerability, pharmacodynamics, and immunologic correlates, have been previously reported. Here, we provide long-term followup on three patients from that trial who sustained objective tumor regressions off therapy, and test the hypothesis that reinduction therapy for late tumor recurrence can be effective. Experimental Design: Three patients with colorectal cancer, renal cell cancer, and melanoma achieved objective responses on an intermittent dosing regimen of BMS-936558. Following cessation of therapy, patients were followed for more than 3 years. A patient with melanoma who experienced a prolonged partial regression followed by tumor recurrence received reinduction therapy. Results: A patient with colorectal cancer experienced a complete response, which is ongoing after 3 years. A patient with renal cell cancer experienced a partial response lasting 3 years off therapy, which converted to a complete response, which is ongoing at 12 months. A patient with melanoma achieved a partial response that was stable for 16 months off therapy; recurrent disease was successfully treated with reinduction anti- PD-1 therapy. Conclusion: These data represent the most prolonged observation to date of patients with solid tumors responding to anti-PD-1 immunotherapy and the first report of successful reinduction therapy following delayed tumor progression. They underscore the potential for immune checkpoint blockade with anti-PD-1 to reset the equilibrium between tumor and the host immune system.
AB - Purpose: Results from the first-in-human phase I trial of the anti-programmed death-1 (PD-1) antibody BMS-936558 in patients with treatment-refractory solid tumors, including safety, tolerability, pharmacodynamics, and immunologic correlates, have been previously reported. Here, we provide long-term followup on three patients from that trial who sustained objective tumor regressions off therapy, and test the hypothesis that reinduction therapy for late tumor recurrence can be effective. Experimental Design: Three patients with colorectal cancer, renal cell cancer, and melanoma achieved objective responses on an intermittent dosing regimen of BMS-936558. Following cessation of therapy, patients were followed for more than 3 years. A patient with melanoma who experienced a prolonged partial regression followed by tumor recurrence received reinduction therapy. Results: A patient with colorectal cancer experienced a complete response, which is ongoing after 3 years. A patient with renal cell cancer experienced a partial response lasting 3 years off therapy, which converted to a complete response, which is ongoing at 12 months. A patient with melanoma achieved a partial response that was stable for 16 months off therapy; recurrent disease was successfully treated with reinduction anti- PD-1 therapy. Conclusion: These data represent the most prolonged observation to date of patients with solid tumors responding to anti-PD-1 immunotherapy and the first report of successful reinduction therapy following delayed tumor progression. They underscore the potential for immune checkpoint blockade with anti-PD-1 to reset the equilibrium between tumor and the host immune system.
UR - http://www.scopus.com/inward/record.url?scp=84872514622&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84872514622&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-12-2625
DO - 10.1158/1078-0432.CCR-12-2625
M3 - Article
C2 - 23169436
AN - SCOPUS:84872514622
SN - 1078-0432
VL - 19
SP - 462
EP - 468
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 2
ER -