Therapeutic vaccines in non-small cell lung cancer

Francisco Socola,1 Naomi Scherfenberg,2 Luis E Raez3 1Division of Hematology/Oncology, Sylvester Comprehensive Cancer Center, University of Miami Leonard M Miller School of Medicine, Miami, Florida, USA; 2University of Miami Leonard M Miller School of Medicine, Miami, Florida, USA; 3Thoracic Oncology Program, Memorial Cancer Institute, Memorial Health Care System, Pembroke Pines, Florida, USA Abstract: Non-small cell lung cancer (NSCLC) unfortunately carries a very poor prognosis. Patients usually do not become symptomatic, and therefore do not seek treatment, until the cancer is advanced and it is too late to employ curative treatment options. New therapeutic options are urgently needed for NSCLC, because even current targeted therapies cure very few patients. Active immunotherapy is an option that is gaining more attention. A delicate and complex interplay exists between the tumor and the immune system. Solid tumors utilize a variety of mechanisms to evade immune detection. However, if the immune system can be stimulated to recognize the tumor as foreign, tumor cells can be specifically eliminated with little systemic toxicity. A number of vaccines designed to boost immunity against NSCLC are currently undergoing investigation in phase III clinical trials. Belagenpumatucel-L, an allogeneic cell vaccine that decreases transforming growth factor (TGF-β) in the tumor microenvironment, releases the immune suppression caused by the tumor and it has shown efficacy in a wide array of patients with advanced NSCLC. Melanoma-associated antigen A3 (MAGE-A3), an antigen-based vaccine, has shown promising results in MAGE-A3+ NSCLC patients who have undergone complete surgical resection. L-BLP25 and TG4010 are both antigenic vaccines that target the Mucin 1 protein (MUC-1), a proto-oncogene that is commonly mutated in solid tumors. CIMAVax is a recombinant human epidermal growth factor (EGF) vaccine that induces anti-EGF antibody production and prevents EGF from binding to its receptor. These vaccines may significantly improve survival and quality of life for patients with an otherwise dismal NSCLC prognosis. This review is intended to give an overview of the current data and the most promising studies of active immunotherapy for NSCLC. Keywords: immunotherapy, non-small cell lung cancer, Belagenpumatucel-L, melanoma-associated antigen A3 (MAGE-A3), L-BLP25, TG4010, CIMAVa

707PSAFETY AND EFFICACY OF NEOADJUVANT FOLFIRINOX IN PATIENTS (PTS) WITH LOCALLY ADVANCED PANCREATIC ADENOCARCINOMA (LAPC)

Abstract Aim: In a retrospective study of 18 pts with unresectable (UR) or borderline resectable (BR) LAPC, neoadjuvant therapy with FOLFIRINOX with or without subsequent chemoradiation (CCRT) resulted in an R0 resection rate (RR) of 44% (Hosein et al, BMC Cancer 2012). The reported 1-year progression-free survival (PFS) was 83 % and the 1-year overall survival (OS) was 100 %. Toxicity profile was tolerable. In order to confirm these preliminary results, we analyzed a large cohort of pts treated in a similar fashion with mature follow-up. Methods: Between 2008 and 2013, 51 treatment-naïve pts with LAPC were treated with first-line FOLFIRINOX with neoadjuvant intent. Pts were categorized as BR or UR using the NCCN criteria. Pts received FOLFIRINOX chemotherapy (at the full dose as described in the ACCORD-11 trial) until maximum response or tolerability, and then underwent surgery if their imaging suggested resectability. Pts then received CCRT if they were still UR or BR after FOLFIRINOX. The end points of this retrospective analysis were OS, PFS, R0 RR and toxicity profile. Results: A total of 429 cycles were given with a median of 8 (range 2-29); 27 (53%) went on to receive CCRT. After a median follow-up of 17 mo (range 2-56), the Kaplan-Meier median OS was 35 mo (95% CI 26-45), the 3-yr OS rate was 42% and the median PFS was 14 mo (95% CI 11 – 16). By imaging criteria, 13 (26%) were converted to resectability and 10 (4 BR and 6 UR) of these had successful R0 resections. Pts who had R0 resections had a significantly longer survival than pts who did not (3-yr OS rate 67% vs 21%, log rank p = 0.042). Grade 1&2/3&4 chemotherapy-related toxicities were neutropenia (39%/20%), neutropenic fever (0%/12%), thrombocytopenia (53%/16%), anemia (63%/10%), fatigue (76%/6%), nausea (57%/4%) vomiting (22%/4%), neuropathy (53%/4%) and diarrhea (37%/10%). Conclusions: FOLFIRINOX followed by chemoradiotherapy is feasible as neoadjuvant therapy in patients with unresectable LAPC. Although the resection rate was only 20%, the median OS of almost 3 years is appreciably longer than historical survival rates for this population. Prospective controlled trials testing this algorithm in LAPC are ongoing. Disclosure: All authors have declared no conflicts of interest