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Background/aim ALK inhibitors like Crizotinib, Ceritinib and Alectinib are targeted therapies used in patients with anaplastic lymphoma kinase (ALK)-positive, advanced non-small cell lung cancer (NSCLC). Since in this tumor entity radiotherapy is employed sequentially or concomitantly, potential synergistic effects were investigated, which may support the hypothesis of induced radiosensitization by using ALK inhibitors. Materials and methods Two cell lines expressing wild-type (WT) or echinoderm microtubule-associated protein-like 4 (EML4)-ALK were treated with ALK inhibitors, followed by irradiation. Cell survival, cell death, cell cycle and phosphorylation of H2A histone family, member X (H2AX) were examined. Results Combined treatment with ALK-inhibitors plus 10 Gy-irradiation led to effects similar to those of sole radiotherapy, but was more effective than sole drug treatment. Conclusion There is no clear evidence of sensitization to radiation by treating EML4-ALK mutated cells with ALK inhibitors.

Background The immune surveillance reactivator lefitolimod (MGN1703), a DNA-based TLR9 agonist, might foster innate and adaptive immune response and thus improve immune-mediated control of residual cancer disease. The IMPULSE phase II study evaluated the efficacy and safety of lefitolimod as maintenance treatment in extensive-stage small-cell lung cancer (ES-SCLC) after objective response to first-line chemotherapy, an indication with a high unmet medical need and stagnant treatment improvement in the last decades. Patients and methods 103 patients with ES-SCLC and objective tumor response (as per RECIST 1.1) following four cycles of platinum-based first-line induction therapy were randomized to receive either lefitolimod maintenance therapy or local standard of care at a ratio of 3 : 2 until progression or unacceptable toxicity. Results From 103 patients enrolled, 62 were randomized to lefitolimod, 41 to the control arm. Patient demographics and response patterns to first-line therapy were balanced. Lefitolimod exhibited a favorable safety profile and pharmacodynamic assessment confirmed the mode-of-action showing a clear activation of monocytes and production of interferon-gamma-induced protein 10 (IP-10). While in the intent-to-treat (ITT) population no relevant effect of lefitolimod on progression-free and overall survival (OS) could be observed, two predefined patient subgroups indicated promising results, favoring lefitolimod with respect to OS: in patients with a low frequency of activated CD86+ B cells (hazard ratio, HR 0.53, 95% CI: 0.26–1.08; n = 38 of 88 analyzed) and in patients with reported chronic obstructive pulmonary disease (COPD) (HR 0.48, 95% CI: 0.20–1.17, n = 25 of 103). Conclusions The IMPULSE study showed no relevant effect of lefitolimod on the main efficacy end point OS in the ITT, but (1) the expected pharmacodynamic response to lefitolimod, (2) positive OS efficacy signals in two predefined subgroups and (3) a favorable safety profile. These data support further exploration of lefitolimod in SCLC.

In 2013 Garon et al published the results of the translational research of the Pointbreak study showing a significant different overall survival (OS) in TTF1- positive adenocarcinomas treated by pemetrexed compared to TTF 1 negative tumors. The aim of this study was to prove whether this finding can be reproduced in not selected real life patients. 57 patients (pts), 26m, 31f, aged 42 to 78, median 64 years with bronchogenic adenocarcinoma undergoing pemetrexed based chemotherapy were analyzed for TTF 1 expression and outcome. 46 (80%) were TTF 1 positive, 11 (20%) TTF 1 negative. There was no statistical difference in age, gender, EGFR mutation status and proportion undergoing maintenance therapy in both groups. Response was different with 48% vs 27% partial remission, 48% vs. 36% stable disease and 4% vs 36% progressive disease in favor of TTF 1 expression (Χ 2 =9,775, p Our results perfectly confirm the data presented by Garon et. al. with only one third of the pts. receiving pemetrexed maintenance in our study.