Abstract P1-17-08: High-dose chemotherapy and immunotherapy in premenopausal breast cancer patients with more than 10 axillary nodes (PBC+10N). Long-term follow-up of a phase II study

Abstract

Abstract Background: PBC+10N have a high risk of relapse. Experimental studies suggest that high expression of vascular endothelial growth factor (VEGF) promotes tumor progression through neoangiogenesis and that natural killer (NK) cells mediate lytic activity against cancer cell lines. In a phase I-II study, we have shown that low-dose interleukin-2 (IL-2) and 13-cis retinoic acid (RA) increased NK cells and decreased VEGF, in patients with advanced cancer and a clinical benefit from chemotherapy (Clin Cancer Res 7: 1251, 2001). We assumed that IL-2 and RA, increasing NK and decreasing VEGF, could improve disease-free survival (DFS) and overall survival (OS) in PBC+10N. Primary endpoint was the evaluation of NK cells and VEGF; secondary endpoints were DFS, OS and toxicity. Methods: 34 patients with PBC+10N, after high-dose chemotherapy and peripheral blood progenitor cell transplantation were entered into the study. They were given hormonal therapy if needed and subcutaneous IL-2, 1.8 X 106 IU and oral RA, 0.5 mg/Kg for 5 days/week, 3 weeks/month, until progression. NK cells, VEGF, response and toxicity were assessed every 4 months. Results: After a median follow-up of 120 months (range 69-209), a total of 41 courses of high-dose chemotherapy and 60 courses of immunotherapy were delivered. A statistically significant improvement of NK cells [from a mean of 302 ± 75/mm3 to a mean of 582 ± 72/mm3 (p < 0.001)] and a decrease of VEGF [from a mean of 525 ± 68 pg/mm3 to a mean of 155 ± 13 pg/mm3, (p < 0.001)], were observed. 18-years DFS and OS were 29% and 32%, respectively. A significant improvement, with respect to NCI SEER data (*), was observed in the 5-year OS rate: 55% vs. 6% No WHO grade 3 or 4 toxicity was observed, while grade 2 cutaneous toxicity and fever occurred in 20% and 13% of patients, respectively. Conclusions: Our data show that immunotherapy with IL-2/RA, may determine, with an acceptable toxicity profile, a statistically significant improvement of NK cells, a decrease of VEGF, and better 5-year survival rates with respect to NCI SEER data. Citation Format: Recchia F, Candeloro G, Rea S. High-dose chemotherapy and immunotherapy in premenopausal breast cancer patients with more than 10 axillary nodes (PBC+10N). Long-term follow-up of a phase II study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-17-08.