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

Abstract

IMPORTANCE Previous 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). OBJECTIVE To 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 PARTICIPANTS An 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 MEASURES Overall survival and PFS and their association with good, intermediate, or poor prognostic LIPI scores. RESULTS Eleven 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 RELEVANCE The 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.

Prognostic value of an inflammatory index for patients with metastatic castration‐resistant prostate cancer

“…37 The combination of inflammatory markers has been shown to be a significant predictive parameter not only for patients who received ICI, but also chemotherapy, in NSCLC. 20 Patients with mCRPC may have a chance to undergo a wide range of treatment sequences, and the combination inflammatory index will be a useful biomarker.…”

“…This study proposed this combined parameter as the lung immune prognostic index (LIPI). In addition, a subsequent study reported that the LIPI is also a valuable biomarker for predicting prognosis in patients receiving chemotherapy, not only ICIs 20 . There is a variety of treatment options in the advanced stages of PCa.…”

“…In addition, a subsequent study reported that the LIPI is also a valuable biomarker for predicting prognosis in patients receiving chemotherapy, not only ICIs. 20 There is a variety of treatment options in the advanced stages of PCa. Potent androgen receptor-targeted therapy and cytotoxic chemotherapy are the current dominant approaches, but the use of combination treatment with immunotherapy is expected to expand in the near future also in PCa.…”

Mass Spectrometry-Based Multivariate Proteomic Tests for Prediction of Outcomes on Immune Checkpoint Blockade Therapy: The Modern Analytical Approach

“…In the case of melanoma patients, we could evaluate the potential interaction between test classifications and NLR [23]-a biomarker of systemic inflammation that has previously shown association with outcomes on ICIs [24,25]. The Kaplan-Meier plots suggested that the difference in outcomes between BDX008 classifications may be qualitatively different in the subgroups defined by NLR: it appeared that patients with NLR <5 classified as BDX008+ had especially good outcomes on anti-PD-1 treatment; while at the same time patients classified as BDX008-had poor prognosis independently of NLR status [46] (Figure 2).…”

“…To date, cell-based surrogate markers for systemic inflammation, such as a neutrophil-to-lymphocyte ratio (NLR) measured in circulation, are most studied and have shown significant prognostic value in cancer [23,24]. An index combining the derived neutrophil/leukocyte-lymphocyte ratio (dNLR) with lactate dehydrogenase (LDH) levels demonstrated strong prognostic potential in NSCLC in different clinical modalities, including immune checkpoint inhibitors [25]. Nonetheless, the predictive potential of these measurements for ICIs relative to other therapies has not been established.…”