A phase III study of belagenpumatucel-L, an allogeneic tumour cell vaccine, as maintenance therapy for non-small cell lung cancer

Abstract

Although the overall trial did not meet its survival endpoint, improved survival for belagenpumatucel-L is suggested in patients who were randomised within 12weeks of completion of chemotherapy and in those who had received prior radiation. Further studies of belagenpumatucel-L in NSCLC are warranted.

Targeting TGF-β Signaling for Therapeutic Gain

“…However, a phase III trial to examine benefit as a NSCLC maintenance therapy following primary treatment (270 Lucanix-treated vs. 262 placebo-treated NSCLC patients) did not meet its primary endpoint criterion of increased overall survival (OS) (Giaccone et al 2015). Stratification of the data revealed a marginal but significant therapeutic benefit for NSCLC patients who started Lucanix within 12 weeks of their initial chemotherapy (166 drug-treated vs. 149 control NSCLC patients), and in those receiving prior radiation therapy (RT), which might boost tumor antigenicity (median survival 28.4 mo for RT with belagenpumatucel-L treatment vs. 16.0 mo for RT plus placebo; HR 0.61, p ¼ 0.032) (Giaccone et al 2015). Nevertheless, the drug is currently not under further clinical development.…”

Adjuvant immunotherapy in resected early non-small cell lung cancer—battle lost, hopefully not the war!

“…Patients were eligible for randomisation between one and four months from the end of induction CHT. Here as well, no difference in either overall survival or progression-free survival was observed between the two treatment groups (22).…”

“…No difference in overall survival was seen in this study accompanied with similar toxicity profile (21). In another vaccination study (22), in advanced (stage III/IV) NSCLC, patients who did not progress after platinum-based CHT were randomised to receive maintenance whole tumor cell vaccine belagenpumatucel-L or placebo. Patients were eligible for randomisation between one and four months from the end of induction CHT.…”

“…What both locally advanced (21) and advanced (22) NSCLC vaccination studies indicated is that effectiveness of previous treatment (concurrent radiochemotherapy being superior to sequential chemoradiotherapy in locally advanced NSCLC and CHT with radiotherapy in advanced NSCLC) may create favorable setting for vaccination success. If so, why then in a subset of patients with the least tumor burden, i.e., resected early NSCLC this did not work?…”

Immunotherapy and Targeted Therapies in the Treatment of Non-small Cell Lung Cancer

“…Although NSCLC was not believed to be an immunogenic malignancy due to lack of efficacy of immunomodulatory cytokines such as interleukin 2 (IL-2) and interferon (IFN), and of early vaccines, [77][78][79] recent data demonstrating the efficacy of immune checkpoint inhibitors have established the importance of the immune response in NSCLC (see Table 2). In addition, neoantigen-reactive tumour-infiltrating T cell lymphocytes (TILs), which can potentially induce tumour regression, were identified in NSCLC.…”