Abstract P4-13-01: A pilot study of pre-operative (Pre-op), single-dose ipilimumab (Ipi) and/or cryoablation (Cryo) in women (pts) with early stage/resectable breast cancer (ESBC)
Authors: Diab A , Solomon SB , Comstock C , Maybody M , Sacchini V , Durack J , Blum B , Yuan J , Patil S , Neville D , Sung J , Kotin A , Morris E , Brogi E , Morrow M , Wolchok J , Allison J , Hudis C , Norton L , McArthur H 
Published: August 2014

Abstract
Background: Intratumoral cryo combined with immune modulation generates a potent systemic anti-tumor immune response that might improve recurrence free survival in ESBC. In this study, we evaluate the safety of pre-op cryo and/or ipi (10mg/kg) in pts with ESBC. Radiographic correlates and intratumoral/serologic immune responses are also explored.
Methods: Eligible pts are ≥18y of age with operable ≥1.5 cm invasive ESBC, no history of autoimmune disease and planned mastectomy. Pts are sequentially assigned to receive pre-op: cryo alone (group-A), ipi alone (B), or ipi with cryo (C). Cryo is performed 7-10d prior to surgery. Ipi is administered 8-15d prior to surgery (1-5d prior to cryo). If at least 5/6 pts in each group proceed with surgery without delay, the regimen will be considered safe/tolerable. Toxicity evaluation continues for 12 wks after ipi administration for groups B and C. Cytokine levels are measured from peripheral blood samples at multiple time points [baseline, at biopsy/cryo (post ipi), at mastectomy, and 30 days post surgery] using MSD® cytokine assay.
Results: As of May 30, 2013, 7/7 pts were enrolled to group A (expanded after a possible technical failure in 1 pt) and 6/6 pts were enrolled to group B. The median age was 45y (range 39-69y). All 13 pts in groups A and B underwent mastectomy without delay. Group C is now accruing with 1/6 patients enrolled and surgery completed without delay. Toxicity and safety: 6/7 pts in group A and 0/6 in group B had ischemic tumor necrosis/infarction in the mastectomy tissue. Overall, pre-op cryo or ipi alone have been well tolerated with no study related grade ¾ adverse events (AE) reported (Table1). Exploratory studies are ongoing for pts who successfully complete the planned intervention. Currently, immune response data is available for 10 pts: 5 from each of groups A and B. Both groups have detectable IL-8 levels which are increased from baseline, interestingly and only in group-B (ipi alone) several pts have preferential increase of IFN-γ and TNF-α (TH1 cytokines) compared to IL-5 and IL-10 (TH2 cytokines). One group B pt who had pre-treatment peri-tumoral lymphocytic infiltrate had prolonged and significantly higher levels of IFN-γ and TNF-α only.
Conclusion: To date, pre-op cryo or ipi is safe and tolerable in pts with ESBC. Preliminary exploratory analyses from groups A and B demonstrated elevated IFN-γ and TNF-α levels in the ipi-treated group. A Phase II study of pre-op ipi and cryo in ESBC is planned.
Table 1All AEsGrade 1Grade 2Grade 3/4Any event130Immune-related AE(Groups B&C)Pruritus/ Rash110GI: Diarrhea/ Colitis010Hepatic000Endocrine000Other (all groups)Local Skin reaction (flap dehiscence)01 *0Fever /Chills000Arthralgias/ Myalgias000Fatigue /Headache000GI/Hepatic000*Cryoablation alone
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-13-01.