Prognostic Value of the Lung Immune Prognostic Index for Patients Treated for Metastatic Non-Small Cell Lung Cancer

Key PointsQuestionDoes the lung immune prognostic index composite (LIPI) score (the derived neutrophil to lymphocyte ratio and the lactate dehydrogenase level) provide prognostic information for patients with metastatic non-small cell lung cancer treated with immune checkpoint inhibitors, targeted therapy, or cytotoxic chemotherapy? FindingsAn exploratory pooled analysis of the LIPI score was performed of data from 11 immune checkpoint inhibitor and targeted therapy clinical trials for metastatic non-small cell lung cancer submitted to the US Food and Drug Administration. The LIPI score was associated with overall survival and progression-free survival among patients receiving either immune checkpoint inhibitors, targeted therapy, or cytotoxic chemotherapy. MeaningBaseline lactate dehydrogenase level and derived neutrophil to lymphocyte ratio may be important prognostic biomarkers irrespective of treatment drug class. ImportancePrevious studies have suggested the importance of the baseline derived neutrophil to lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) level as prognostic markers. The lung immune prognostic index (LIPI) was shown to be associated with progression-free survival (PFS) and overall survival (OS) among patients with metastatic non-small cell lung cancer (mNSCLC) treated with immune checkpoint inhibitors (ICIs) but not cytotoxic chemotherapy (CCT). ObjectiveTo determine whether the LIPI is associated with long-term outcomes in pooled analyses of clinical studies of ICI and targeted therapy (TT) for patients with mNSCLC. Design, Setting, and ParticipantsAn exploratory pooled analysis was performed of the LIPI on data from 11 randomized clinical multinational trials evaluating ICIs and TT submitted to the US Food and Drug Administration between January 1, 2013, and December 31, 2017, for 4914 patients with mNSCLC. Lung immune prognostic index scores were calculated based on the dNLR and the LDH level per previous publications to generate good, intermediate, and poor composite scores. Multivariable Cox proportional PFS and OS hazard ratios were generated for the dNLR, the LDH level, age, smoking status, histologic characteristics, and Eastern Cooperative Oncology Group performance score. Main Outcomes and MeasuresOverall survival and PFS and their association with good, intermediate, or poor prognostic LIPI scores. ResultsEleven mNSCLC randomized trials were analyzed, including 3987 patients with available data. In 5 ICI trials comprising 2440 patients, 1368 patients received ICIs and 1072 patients received CCT. In 6 TT trials comprising 1547 patients, 1110 patients received TT and 437 patients received CCT. A good LIPI score was associated with better OS among patients receiving ICIs (hazard ratio, 0.34; 95% CI, 0.28-0.42), TT (hazard ratio, 0.28; 95% CI, 0.21-0.37), and CCT (hazard ratio, 0.49; 95% CI, 0.40-0.60 in ICI trials; hazard ratio, 0.41; 95% CI, 0.27-0.61 in TT trials) than those with poor LIPI scores. Similar findings were observed in terms of PFS (ICIs: hazard ratio, 0.59; 95% CI, 0.48-0.72; TT: hazard ratio, 0.46; 95% CI, 0.37-0.57; and CCT: hazard ratio, 0.56; 95% CI, 0.45-0.68 in ICI trials; hazard ratio, 0.51; 95% CI, 0.38-0.69 in TT trials). Conclusions and RelevanceThe baseline LDH level and dNLR are important prognostic biomarkers irrespective of treatment modality for patients with mNSCLC. As further prospective clinical trial information is collected, the role of the LIPI score can be better defined. This exploratory pooled analysis of 11 randomized clinical trials examines whether the lung immune prognostic index is associated with long-term outcomes of treatment with immune checkpoint inhibitors and targeted therapy for patients with metastatic non-small cell lung cancer.