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PD-1/PD-L1 Blockade Combined with AbnobaViscum Therapy is Linked to Improved Survival in Advanced or Metastatic NSCLC Patients, an ESMO-GROW Related Re-al-World Data Registry Study

Schad, F.; Thronicke, A.; Hofheinz, R.-D.; Klein, R.; Grabowski, P.; Oei, S. L.; Wuestefeld, H.; Grah, C.

2024-10-24 oncology
10.1101/2024.10.24.24316043 medRxiv
Show abstract

BackgroundRecent advancements in cancer treatment have shown the potential of PD-1/PD-L1 inhibitor (ICB) plus Viscum album L. (VA) therapy in improving survival rates for patients with advanced or metastasized non-small cell lung cancer (NSCLC). The objective of this study was to investigate factors associated with improved survival in NSCLC patients treated with a combination of ICB and VA. MethodsPatients with advanced or metastasized NSCLC from the accredited national Network Oncology registry were included in the real-world data study adhering to ESMO-GROW criteria. The study was conducted with ethics approval. Survival and the impact on hazard were compared between patients receiving PD-1/PD-L1 inhibitor therapy alone versus combinational PD-1/PD-L1 inhibitors and abnobaViscum(R) therapy. Adjusted multivariate Cox proportional hazard analysis was utilized to examine factors linked to survival. ResultsEnrolled patients (n = 300) had stage III or stage IV NSCLC, had a 1.19 male/female ratio and were 68 years old (median). Two hundred and twenty-two patients (74%) were in the control (CTRL, PD-1/PD-L1 inhibitor therapy) and seventy-eight patients (26%) in the combinational (COMB, PD-1/PD-L1 inhibitor plus abnobaViscum(R) therapy) group. The three-year survival was significantly prolonged by 7 months when abnobaViscum(R) therapy was added to the anti-PD-1/PD-L1 therapy (Comb: 13.8 months vs. Control: 6.8 months, p = 0.005). The three-year survival rate was 16.5% in the COMB group and two times higher than the three-year survival rate in the CTRL group (8.0%). Adjusted multivariable Cox regression analysis was performed for patients with PD-L1 positive ([≥]1%) NSCLC treated with a first-line PD-1 inhibitor and revealed that the addition of abnobaViscum(R) therapy to anti-PD-1 significantly lowered the hazard of death by 75% in (aHR: 0.25; 95%CI: 0.11-0.60, p=0.002). ConclusionsOur results indicate that addition of abnobaViscum(R) therapy is significantly linked to enhanced survival in patients with advanced or metastasized NSCLC who are undergoing treatment with standard PD-1/PD-L1 inhibitor therapy irrespective of their age, tumor stage, ECOG status, surgery or radiation. The mechanisms could involve a synergistic modulation of the immune response, reduced primary PD-1/PD-L1 inhibitor resistance via immunogenic cell death and/or modification of the tumor microenvironment by combinational PD-1/PD-L1 inhibitor and abnobaViscum(R) therapy. Our findings should be complemented with analyses of RCT or R-RCT. Trial registrationThe study was registered retrospectively (DRKS00013335).

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