Abstract 480: Maintenance immunotherapy following carboplatin (CBDCA) - pemetrexed (PEM) chemotherapy in advanced adenocarcinoma (ADK) of the lung: A phase II study.
Authors: Recchia Francesco , Candeloro Giampiero , Cesta Alisia , Di Blasio Anna , Recchia Cornelia O.C. , Necozione Stefano , Desideri Giovambattista , Rea Silvio 
Published: August 2014

Background: Continuation maintenance therapy with PEM vs. placebo has been shown to improve progression-free survival (PFS) and overall survival (OS), in patients with advanced non squamous non small cell lung cancer, at the price of a substantial toxicity. Nevertheless, in these patients the observed lymphocytopenia induced by chemotherapy, is a negative independent prognostic factor. Bacterial extracts (OM-85) have been shown to enhance the activation of both IgM memory B lymphocytes (CD24+/CD27+ cells) and inteleukin-2 receptor-expressing lymphocytes (CD25+ cells) (Int J Immunopathol Pharmacol. 2006;19:551). In addition, we have demonstrated that 13-cis retinoic acid (RA) restored the chemotherapy-depressed immune function (Clin Cancer Res 2001;7:1251). With this rationale, we designed a phase II study of maintenance immunotherapy after first line CBDCA-PEM chemotherapy in order to maintain an achieved response, or at least stable disease, for as long as possible, with acceptable side effects.

Methods: Histologically/cytologically confirmed patients with stage IIIB or IV non operable ADK of the lung with measurable disease, ECOG PS 0-2, age 18-75 years and adequate bone marrow, renal and liver function were eligible for the study. Treatment consisted of 6 courses of PEM 500 mg/m2 and CBDCA, AUC=5, on day 1 every 3 weeks. Patients with a clinical benefit were treated with OM-85, 7 mg/day, 10 days/month and RA 0.5 mg/kg, 5 days/week, 3 weeks/month, both given until progression.

Results: From September 2007 to March 2012, 54 patients, with a median age of 65 years (range 33-75), 50% stage IIIB and 50% stage IV, were entered into the study. At a median follow up of 22 months, clinical benefit was observed in 41 patients (75%); Complete response 8 (14%), partial response 21 (39%), stable disease 12 (22%), progressive disease 13 (25%). One-year OS rate was 69%. After immunotherapy, a statistically significant (P&lt;0.001) increase in lymphocyte number was observed in responders. Median PFS was 10.2 months, while median OS was 27.6 months. Four patients, rendered operable with treatment, underwent a radical surgical procedure. Grade 4 renal toxicity was observed in 1 patient, while grade 3-4 hematologic toxicity occurred in 9 patients (17%).

Conclusion: This study shows that maintenance immunotherapy with the combination of OM-85 and RA, administered after chemotherapy in advanced ADK of the lung, is feasible and induces a statistically significant raise in lymphocyte number. In addition a favorable impact on PFS and OS was observed. Future randomized studies to investigate the role of maintenance immunotherapy strategies, are in program

Citation Format: Francesco Recchia, Giampiero Candeloro, Alisia Cesta, Anna Di Blasio, Cornelia O.C. Recchia, Stefano Necozione, Giovambattista Desideri, Silvio Rea. Maintenance immunotherapy following carboplatin (CBDCA) - pemetrexed (PEM) chemotherapy in advanced adenocarcinoma (ADK) of the lung: A phase II study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 480. doi:10.1158/1538-7445.AM2013-480