Abstract P6-16-06: Maintenance immunotherapy in estrogen receptor negative (ER-) locally advanced (LA) and/or metastatic breast cancer (MBC). Long-term follow-up of a phase II study
Authors: Recchia F , Candeloro G , Rea S 
Published: March 2017

Abstract
Background: Cancer immunotherapy is revolutionizing treatment today. While MBC with estrogen receptor positive (ER+) tumors, responding or stabilizing after first line chemotherapy, may have a benefit from a maintenance endocrine therapy combined with the monoclonal antibody bevacizumab, no option exists for ER- patients. In the past, we have shown, that a combination of 13-cis retinoic acid (RA) and interleukin-2 (IL-2) was able to improve the immune function [enhancing lymphocyte and natural killer cell (NK) counts, and CD4+/CD8+ ratio] of cancer patients who had had a clinical benefit from chemotherapy (Clin Cancer Res 2001;7:1251). With the aim of improving the immune function which eventually would lead to improvement of progression free survival (PFS) and overall survival (OS), patients with ER- LA or MBC, with a clinical benefit from chemotherapy, were treated with a combination of IL-2 and RA. Methods: Eligible patients with ER-, LA or MBC, and no evidence of progression after induction chemotherapy received the following immunotherapy: IL-2, (1.8 M UI ), and oral RA (0.5 mg/kg), 5 days/week, 3 weeks/month for 1 year. Therapy was continued, with intermittent schedule until progression. Primary endpoints were the differences in lymphocyte , natural killer cell (NK) counts, and CD4+/CD8+ ratio, secondary end points were progression free survival (PFS), overall survival (OS) and toxicity. Results: From 12/1996 to 04/2009, 74 patients with ER-, LA (49%) or MBC (51%) were entered into the study. Median age was 55 years (range 31-75), 31% of patients were pre-menopausal. Each patient had received a median of 11 courses of first line and salvage chemotherapy regimens (total 850 courses). In addition, 31 patients had received high-dose chemotherapy with peripheral blood progenitor cell transplantation. Disease sites were as follows: soft tissue 54%, viscera 28%, bones 18%. After a median follow-up of 118 months (range 84-232), a total of 374 courses of immunotherapy were delivered. No WHO grade 3 or 4 toxicity was observed; grade 2 cutaneous toxicity and autoimmune reactions occurred in 19% and 16% of patients, respectively. A Statistically significant improvement with respect to baseline values was observed in the number of lymphocytes (p&lt;0.001), NKs (p&lt;0.001), and the CD4+/CD8+ ratio (p&lt;0.01). Median PFS and OS were 44.9 months and 104.8 months, respectively. Conclusions: Maintenance immunotherapy with IL-2 and RA in ER- LA or MBC patients who do not progress after induction chemotherapy is well tolerated, improves lymphocyte, NK, CD4+/CD8+ ratios, and seems to delay disease recurrence.
Citation Format: Recchia F, Candeloro G, Rea S. Maintenance immunotherapy in estrogen receptor negative (ER-) locally advanced (LA) and/or metastatic breast cancer (MBC). Long-term follow-up of a phase II study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-16-06.