TY - JOUR
T1 - A pilot study of preoperative single-dose ipilimumab and/or cryoablation in women with early-stage breast cancer with comprehensive immune profiling
AU - McArthur, Heather L.
AU - Diab, Adi
AU - Page, David B.
AU - Yuan, Jianda
AU - Solomon, Stephen B.
AU - Sacchini, Virgilio
AU - Comstock, Christopher
AU - Durack, Jeremy C.
AU - Maybody, Majid
AU - Sung, Janice
AU - Ginsberg, Arielle
AU - Wong, Phillip
AU - Barlas, Afsar
AU - Dong, Zhiwan
AU - Zhao, Chunjun
AU - Blum, Brian
AU - Patil, Sujata
AU - Neville, Deirdre
AU - Comen, Elizabeth A.
AU - Morris, Elizabeth A.
AU - Kotin, Alan
AU - Brogi, Edi
AU - Wen, Y. Hannah
AU - Morrow, Monica
AU - Lacouture, Mario E.
AU - Sharma, Padmanee
AU - Allison, James P.
AU - Hudis, Clifford A.
AU - Wolchok, Jedd D.
AU - Norton, Larry
N1 - Publisher Copyright:
© 2016 American Association for Cancer Research.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Purpose: To assess the safety and tolerability of preoperative cryoablation-mediated tumor antigen presentation and/or ipilimumab- mediated immune modulation in women with operable breast cancer. Experimental Design: In this pilot study, 19 women with breast cancer for whom mastectomy was planned were treated with preoperative tumor cryoablation (n = 7), single-dose ipilimumab at 10 mg/kg (n = 6), or both (n = 6). The primary outcome for this pilot study was safety/tolerability as defined as freedom from delays in pre-planned, curative-intent mastectomy. Exploratory studies of immune activationwere performed on peripheral blood and tumor. Results: Preoperative cryoablation and/or ipilimumab were safe and tolerable, with no delays in pre-planned surgery. Grade III toxicity was seen in 1 of 19 (unrelated rash after ipilimumab). Combination therapy was associated with sustained peripheral elevations in: Th1-type cytokines, activated (ICOS+) and proliferating (Ki67+) CD4+ and CD8+ T cells, and posttreatment proliferative T-effector cells relative to T-regulatory cells within tumor. Conclusions: Preoperative cryoablation and single-dose ipilimumab are safe alone or in combination with no surgical delays incurred. Potentially favorable intratumoral and systemic immunologic effects were observed with the combination, suggesting the possibility for induced and synergistic antitumor immunity with this strategy.
AB - Purpose: To assess the safety and tolerability of preoperative cryoablation-mediated tumor antigen presentation and/or ipilimumab- mediated immune modulation in women with operable breast cancer. Experimental Design: In this pilot study, 19 women with breast cancer for whom mastectomy was planned were treated with preoperative tumor cryoablation (n = 7), single-dose ipilimumab at 10 mg/kg (n = 6), or both (n = 6). The primary outcome for this pilot study was safety/tolerability as defined as freedom from delays in pre-planned, curative-intent mastectomy. Exploratory studies of immune activationwere performed on peripheral blood and tumor. Results: Preoperative cryoablation and/or ipilimumab were safe and tolerable, with no delays in pre-planned surgery. Grade III toxicity was seen in 1 of 19 (unrelated rash after ipilimumab). Combination therapy was associated with sustained peripheral elevations in: Th1-type cytokines, activated (ICOS+) and proliferating (Ki67+) CD4+ and CD8+ T cells, and posttreatment proliferative T-effector cells relative to T-regulatory cells within tumor. Conclusions: Preoperative cryoablation and single-dose ipilimumab are safe alone or in combination with no surgical delays incurred. Potentially favorable intratumoral and systemic immunologic effects were observed with the combination, suggesting the possibility for induced and synergistic antitumor immunity with this strategy.
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U2 - 10.1158/1078-0432.CCR-16-0190
DO - 10.1158/1078-0432.CCR-16-0190
M3 - Article
C2 - 27566765
AN - SCOPUS:85006325446
SN - 1078-0432
VL - 22
SP - 5729
EP - 5737
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 23
ER -