Details

Autor(en) / Beteiligte

• Heudobler, D
• Schulz, C
• Fischer, J R
• Staib, P
• Wehler, T
• Südhoff, T
• Schichtl, T
• Wilke, J
• Hahn, J
• Lüke, F
• Vogelhuber, M
• Klobuch, S
• Pukrop, T
• Herr, W
• Held, S
• Beckers, K
• Bouche, G
• Reichle, A

Titel

1570PPioglitazone and clarithromycin combined with metronomic low-dose chemotherapy versus nivolumab in patients with advanced non-small cell lung cancer treated in 2nd-line and beyond: Outcomes from a randomized phase II trial (ModuLung)

Ist Teil von

• Annals of oncology, 2019-10, Vol.30 (Supplement_5)

Ort / Verlag

Oxford University Press

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Abstract Background The ModuLung trial addresses the medical need for low-toxic therapies in frequently comorbid patients with relapsed or refractory non-small cell lung cancer (NSCLC). We evaluated safety and efficacy of a biomodulatory approach in > =2nd-line, aiming for induction of anakoinosis i.e. communicative reprogramming of dysregulated cellular and intercellular homeostasis. Methods Patients with stage IIIB/IV squamous or non-squamous NSCLC and disease progression during or after at least one platinum-based chemotherapy were stratified according to histology, and randomly assigned 1:1 to treosulfan 250 mg twice daily, pioglitazone 45 mg once daily and clarithromycin 250 mg twice daily (experimental arm) or nivolumab 3 mg/kg every 2 weeks (control arm). The primary endpoint was progression-free survival (PFS). Results Due to the approval of checkpoint inhibitors in first-line, the study was prematurely closed after randomization of 40 of the 86 initially planned patients. The main efficacy and safety results are presented in the table and show no statistically significant difference between groups. The two-year survival rate achieved in the biomodulatory arm was 10% (95% CI, 1.2 to 31.7) and 5.9% (95% CI, 0.1 to 28.7) in the nivolumab arm. 75% and 53% of the patients proceeded to a further line of therapy, respectively. Table:1570PResultsBiomodulatory Arm (n = 20) 35% > 2nd-lineNivolumab Arm (n = 17) 41.2% > 2nd-lineHR & 95% CI or p-valuePFS, median in months1.62.1HR = 1.17; 95% CI, 0.59--2.34OS, median in months8.26.9HR = 0.86; 95% CI, 0.38-1.96ORR, n (%)2 (10%)0 (0%)P = 0.49Grade 3-5 AE, n (%)2 (10%)6 (35%)P = 0.11 Conclusions Combination of clarithromycin, pioglitazone and metronomic chemotherapy is active in the > =2nd line treatment of NSCLC and warrants further investigations. Nivolumab did not induce any tumor response and was relatively toxic in this population. Novel treatment approaches are urgently needed for patients who previously received platinum-based chemotherapy for advanced squamous and non-squamous NSCLC (Funded by Anticancer Fund, EudraCT number 2014-004095-31). Clinical trial identification EudraCT: 2014-004095-31, Start Date: 2015-07-13. Legal entity responsible for the study Freistaat Bayern respresented by University of Regensburg represented by Kaufmännischer Direktor. Funding Anticancer Fund, Brussels, Belgium. Disclosure All authors have declared no conflicts of interest.