Abstract 5568: Neoadjuvant immunotherapy for solid tumors

Abstract

Abstract Background Cancer surgery remains the most effective single treatment modality for curing patients with solid tumors. However, only half of all cancer patients undergo curative resection. Of those, a significant number will eventually relapse from occult metastases. Administration of therapy prior to surgery, known as neoadjuvant therapy, has revolutionized cancer surgery. It not only decreases overall tumor burden, rendering previously inoperable disease operable, but also improves survival by providing systemic disease control in patients at high risk of having microscopic distant metastases at the time of surgery. While traditional neoadjuvant therapy using conventional chemotherapy and radiation therapy has improved patient outcomes across a spectrum of solid tumors, the potential of neoadjuvant immunotherapy is currently unknown. Various immune modulating agents have achieved significant clinical success in the management of metastatic and treatment resistant cancers, yet their utility in the neoadjuvant setting remains unclear. In theory, neoadjuvant immunotherapy is particularly interesting because it utilizes the primary tumor as a rich source of antigens for T cell priming. As a result, it may be successful in eliciting an immune response where adjuvant immunotherapy treatment has failed. Here we designed a preclinical study utilizing neoadjuvant immunotherapy and demonstrate the efficacy of employing immune stimulating agents synergistically with surgical resection. Methods We used two different murine models of solid tumors – a metastatic triple negative breast carcinoma and a colorectal carcinoma to compare neoadjuvant immunotherapy, resection alone, or immunotherapy alone treatments on local and systemic disease control, and survival. We found that neoadjuvant immunotherapy offered the best survival as well as the best locoregional and metastatic disease control when compared to the other groups. In fact, in the highly aggressive and spontaneously metastatic breast carcinoma model the neoadjuvant treatment group was the only group in which a long-term surviving cohort of mice was cured. When these long-term survivors were rechallenged with the same tumor, they were immune, confirming that the treatment successfully conferred immunological memory. When exposed to a new tumor type, however, they remained susceptible, confirming the specificity of this immunologic memory. Disease control was found to be T cell dependent as depletion of either both CD4+ and CD8+, or CD8+ only T cells resulted in loss of therapeutic benefit in mice treated with neoadjuvant immunotherapy. Conclusion We found that neoadjuvant immunotherapy successfully initiated cell mediated antitumor activity both locally and systemically at an anatomically distant disease site. This resulted in improved survival in the neoadjuvant group when compared to groups receiving resection alone or immunotherapy alone. As increased options to incorporate immunotherapy in the clinic become available to clinicians, this study explores the timely and clinically important question of how immunotherapy may optimally be combined with surgical resection. The results of the study are readily translatable and may be utilized to inform establishment of neoadjuvant immunotherapy regimens for patients with early stage and locally advanced solid tumors. Citation Format: Wan Xing Hong, Idit Sagiv-Barfi, Debra Czerwinski, Ronald Levy. Neoadjuvant immunotherapy for solid tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5568.