Combined Immune Checkpoint Blockade and Helixor® Therapy in Oncology: Real-World Tolerability and Subgroup Survival (ESMO GROW)

Abstract

Real-world data (RWD) play a crucial role in identifying key subgroups and assessing multimodal oncology therapies, including integrative and palliative care. Immune checkpoint blockade (ICB) has improved survival, and its combination with complementary therapies like Viscum album L. extracts (VA) may enhance outcomes. This RWD study, based on the Network Oncology registry and ESMO-GROW guidelines, analyzed oncological patients receiving PD-1/PD-L1 inhibitors alone or with Helixor^® VA (HVA) extracts. Primary and secondary objectives were tolerability and overall survival. Statistical analyses included Kaplan-Meier survival curves and Cox regression. Among 405 cancer patients, 344 received ICB alone (CTRL) and 61 received ICB + HVA (COMB). Lung cancer was predominant (78.6%). Adverse event-related discontinuation was lower in COMB (4.9% vs. 6.4%, p = 0.25). In non-small cell lung cancer (NSCLC) patients, the 3-year survival rate was significantly higher in COMB (34.3% vs. 17.2%, p = 0.02). In female NSCLC patients, COMB was significantly associated with a reduced death risk of 91.2% (aHR: 0.088; 95% CI: 0.009-0.783). Our RWD findings show the favorable tolerability of combinatorial ICB + HVA in several tumor entities and underscore its potential to improve survival in NSCLC particularly in female NSCLC patients, warranting further investigation.

Keywords: Helixor® Viscum album therapy; PD-1 inhibitor; PD-L1 inhibitor; lung cancer; non-small cell lung cancer; survival.

Figure 1

Study process flow. Oncological patients with ICB plus HVA or not, (n = 405), CTRL, ICB without HVA; COMB, ICB with HVA; ICB, immune checkpoint blockade; n, number; HVA, Helixor^® Viscum album therapy.

Figure 2

Discontinuation of ICB due to adverse events (n = 405), CTRL, ICB without HVA; COMB, ICB with HVA; ICB, immune checkpoint blockade; n, number; HVA, Helixor^® Viscum album therapy.

Figure 3

Kaplan–Meier survival analysis for overall survival in patients with NSCLC (n = 312); Log-rank test: X² = 1.8, p = 0.2; CTRL, PD-1/PD-L1 inhibitors COMB, PD-1/PD-L1 inhibitors with HVA therapy; NSCLC, non-small cell lung cancer.

Figure 4

Kaplan–Meier survival analysis (overall survival) for female NSCLC patients treated with PD-1/PD-L1 inhibitors with or without Helixor^® VA (HVA) therapy (n = 137); Log-rank test: X² = 3.6, p = 0.06; CTRL, PD-1/PD-L1 inhibitors COMB, PD-1/PD-L1 inhibitors with HVA therapy; NSCLC, non-small cel7l lung cancer.

Figure 5

Cox proportional hazard analysis. Subgroup female patients with NSCLC (n = 137). Adjusted for standard oncological immune checkpoint therapy, stratified for age, tumor stage, and first-line therapy. Therapies with a hazard ratio less than 1 (to the left of 1) are considered to reduce mortality, while those with a hazard ratio greater than 1 (to the right of 1) are considered to increase mortality. The combinational ICB + HVA therapy reveals a significant reduction of hazard of death by 91.2%, p = 0.029 (aHR: 0.088, 95%CI: 0.009 to 0.783); aHR, adjusted hazard ratio; CI, confidence interval. ICB, immune checkpoint blockade; HVA, Helixor^® VA; NSCLC, non-small cell lung cancer.