Prognostic and predictive value of neutrophil-to-lymphocyte ratio with adjuvant immunotherapy in stage III non-small-cell lung cancer.

BACKGROUND

Elevated pre-treatment neutrophil-to-lymphocyte ratio (NLR) may reflect immune dysfunction and is negatively prognostic in cancer patients treated with immunotherapy, but it is unclear if NLR is predictive of immunotherapy benefit.

METHODS

We identified stage III non-small-cell lung cancer (NSCLC) patients treated with definitive chemoradiation and adjuvant durvalumab within the national Veterans Affairs system from 2017 to 2021. We compared the prognostic value of NLR measured before durvalumab start to a control group of stage III NSCLC patients treated with definitive chemoradiation alone from 2015 to 2016 (no-durvalumab group) before the approval of adjuvant durvalumab. We estimated the predictive value of NLR through the statistical interaction of durvalumab group by NLR level. Outcomes included progression-free survival (PFS) and overall survival (OS).

RESULTS

The primary analysis for NLR included 821 durvalumab patients and 445 no-durvalumab patients. Higher NLR was associated with inferior PFS in both groups (no-durvalumab: adjusted HR [aHR] 1.14 per 7.43 unit increase in NLR, 95% confidence interval [CI] 1.06-1.23; durvalumab: aHR 1.42, 95% CI 1.23-1.64), though this effect was greater in durvalumab patients (p for interaction = 0.009). Similar results were found for OS (no-durvalumab: aHR 1.16, 95% CI 1.09-1.24; durvalumab: aHR 1.48, 95% CI 1.25-1.76; p for interaction = 0.010). Absolute lymphocytes, eosinophils, and basophils were not prognostic in either group. Estimates of durvalumab treatment efficacy suggested declining efficacy with higher NLR.

CONCLUSION

Pre-treatment NLR is especially prognostic among stage III NSCLC patients treated with adjuvant immunotherapy compared to control patients treated without immunotherapy and may be a predictive biomarker of immunotherapy benefit.