Clinical predoctors of immune checkpoint inhibitor efficacy in non-small cell lung cancer

Background Treatment with immune checkpoint inhibitors (ICI) prolongs overall survival OS and confers long-term disease control in 15 – 20% of non-small cell lung cancer (NSCLC) patients. Patient selection currently depends on the levels of PD-L1 expression, but correlation with outcome is weak.

Patients and Methods We retrospectively analyzed the clinical course of ICI-treated stage IV NSCLC patients at our institution.

Results A total of 453 patients were identified with a median age of 64 years having received nivolumab (57%), pembrolizumab (35%), PD-L1 inhibitors (7%) or various combinations with chemotherapy or CTLA4 blockade (1%). Progression-free survival (PFS) under ICI was significantly longer for patients receiving ICI in the first (21%) compared to second (47%) and later treatment lines (p < 0.001), for current and ex-smokers (91% of cases, p = 0.034), in case of adenocarcinoma (66%) compared to squamous cell carcinoma (28%) and other histologies (9%, p < 0.001), while age, sex and ECOG status at initial diagnosis had no influence. Presence of liver metastases at diagnosis was associated with shorter ICI responses (p < 0.01), while other metastatic sites did not play a role. Blood markers, like the Lymphocyte-to-Neutrophile-Ratio (LNR) as well as CRP and LDH as indicators of inflammation and tumor load, had the highest discriminatory value (≥ 3× longer median PFS under ICI for cases with higher LNR or lower CRP or LDH, p < 0.0001 for each). Tumors with PD-L1 < 1% vs. 1 – 49% (14% and 34%, respectively) showed similar durations of ICI benefit, while cases with PD-L1 expression > 50% had an ICI-PFS twice as long (p = 0.0105).

Conclusions Several clinical and blood parameters appear to correlate with ICI benefit in NSCLC patients and could be used along with tissue PD-L1 expression and molecular markers in order to improve predictive tools for lung cancer immunotherapy.