Background: Opioids seem to interfere with immune response. We analysed the prognostic and predictive impact of opioids in Non Small Cell Lung Cancer (NSCLC) patients treated with immunotherapy.
Methods: We retrospectively collected and analyzed data about NSCLC patients treated with anti-PD-1/anti-PD-L1 agents at our Institution. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. A Cox regression model was carried out for univariate and multivariate analyses.
Results: Sixty-six patients were enrolled, 50 male (75.8%) and 16 female (24.2%). Median age was 72 years (range 25-88). Thirty-one patients (47%) received opioids at the beginning and/or during immunotherapy. This setting of patients had a poorer prognosis (mOS 5.37 months vs not reached, p= 0.0009; mPFS 3.83 months vs not reached, p=0.0001). Performance Status (PS) according to Eastern Cooperative Oncology Group (ECOG) had a prognostic and predictive role (mOS 3.23 months vs not reached, p=0.0059; mPFS of 1.7 vs 3.8 months, p= 0.0089). Sex, age (cut-off 70 years), lymphopenia, PD-L1 expression did not result as prognostic and predictive factors. Multivariate analysis confirmed that opioids had a negative prognostic and predictive role and ECOG-PS ≥2 had a negative prognostic impact. Patients requiring higher opioids doses or opioids switch had a lower survival (OS 4.9 vs 16.5 months; p=0.0030). A trend of worse prognosis was observed in patients receiving morphine (mOS 4.1 vs 8.6 months, p= 0.059) and fentanyl (mOS 4.17 vs 8.63 months).
Conclusion: Opioid treatment and its escalation at the beginning and during immunotherapy are negative prognostic factors in advanced NSCLC.