Predicting outcomes in patients with advanced non-small cell lung cancer enrolled in early phase immunotherapy trials

Maymani, Hossein; Hess, Kenneth R.; Groisberg, Roman; Hong, David S.; Naing, Aung; Piha-Paul, Sarina A.; Janků, Filip; Fu, Siqing; Tsimberidou, Apostolia M.; Pant, Shubham; Karp, Daniel D.; Liu, Shuang; Sun, Ming; Heymach, John V.; Simon, George R.; Meric‐Bernstam, Funda; Subbiah, Vivek

doi:10.1016/j.lungcan.2018.03.020

Cited by 31 publications

(33 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We summarized the characteristics in Table 1. Of all included studies, five were performed in the United States (7,31,33,34,40), four in Japan (32,36,39,44), and the remaining eight studies were conducted in Switzerland (35), Canada (37), France (38,45), Bulgaria (41), China (42), Germany (43), and Italy (46), respectively. In terms of the ICIs used, 11 studies reported on nivolumab (7, 31-36, 39, 42, 45, 46), 2 studies reported on pembrolizumab (41,44), and the remaining 4 studies did not specify the type of ICIs (37,38,40,43).…”

Section: Characteristics Of Eligible Studies and Quality Assessmentmentioning

confidence: 99%

Pretreatment Neutrophil-to-Lymphocyte Ratio (NLR) May Predict the Outcomes of Advanced Non-small-cell Lung Cancer (NSCLC) Patients Treated With Immune Checkpoint Inhibitors (ICIs)

Zhang

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

HR = 1.71; 95% CI 1.18-2.46; P < 0.001) compared with those with NLR < 6.0. The associations between NLR and survival were consistent in subgroup analysis stratified by age, gender, ECOG PS, histology, stage, smoking history, treatment, and prior lines of therapy. Dynamics of NLR (dNLR) that increased ≥3.0 from baseline was also significantly associated with worse PFS (median: 3.1 vs. 9.1 months; P = 0.01) and OS (median: 6.8 vs. 17.0 months; P < 0.0001). Conclusions: Our study demonstrates that pretreatment NLR and dNLR from baseline are associated with the outcomes of advanced NSCLC patients treated with ICIs; however, it warrants further prospective studies.

show abstract

Section: Characteristics Of Eligible Studies and Quality Assessmentmentioning

confidence: 99%

Pretreatment Neutrophil-to-Lymphocyte Ratio (NLR) May Predict the Outcomes of Advanced Non-small-cell Lung Cancer (NSCLC) Patients Treated With Immune Checkpoint Inhibitors (ICIs)

Zhang

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…The NLR has been previously associated with disease control and treatment response to checkpoint inhibitors in NSCLC. 5,6 To strengthen the prognostic power of the derived NLR (dNLR), a surrogate for the NLR, in NSCLC, Mezquita and colleagues 7 recently generated a lung immune prognostic index (LIPI) based on 161 patients who received immune checkpoint inhibitors (ICIs), specifically programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors. This composite index included a dNLR greater than 3 and an LDH level higher than the upper limit of normal, which characterized 3 risk groups: good, intermediate, and poor.…”

mentioning

confidence: 99%

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

et al. 2019

View full text Add to dashboard Cite

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.

show abstract

“…Emerging evidence indicates that pretreatment NLR is a prognostic marker for a wide range of malignancies, with NLR values of >4 or>5 being associated with worsening OS and/or diseasefree survival. [22][23][24] Results from retrospective analyses of patients with melanoma and NSCLC were also suggestive of NLR having potential predictive value in the response to immunotherapy. 25 26 To date, the underlying biological mechanism of NLR as a novel biomarker is unclear and efforts are underway to elucidate this.…”

Section: Discussionmentioning

confidence: 99%

Effect of cyclo-oxygenase inhibitor use during checkpoint blockade immunotherapy in patients with metastatic melanoma and non-small cell lung cancer

Wang

Khullar

Kim

et al. 2020

J Immunother Cancer

Self Cite

View full text Add to dashboard Cite

BackgroundImmune checkpoint inhibitors (ICIs) improve survival outcomes in metastatic melanoma and non-small cell lung cancer (NSCLC). Preclinical evidence suggests that overexpression of cyclo-oxygenase-2 (COX2) in tumors facilitates immune evasion through prostaglandin E2 production and that COX inhibition synergizes with ICIs to promote antitumor T-cell activation. This study investigates whether concurrent COX inhibitor (COXi) use during ICI treatment compared with ICI alone is associated with improved time-to-progression (TTP), objective response rate (ORR) and overall survival (OS) in patients with metastatic melanoma and NSCLC.MethodsWe retrospectively reviewed 90 metastatic melanoma and 37 metastatic NSCLC patients, treated with ICI between 2011 and 2019. Differences in TTP and OS by ICI+COXi versus ICI alone were compared using Kaplan-Meier and Cox regression. Interaction between ICI+COXi versus ICI alone and pretreatment neutrophil–lymphocyte ratio (NLR) was examined. Independent radiology review per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was performed.ResultsFor patients with melanoma, median TTP was significantly prolonged in ICI+COXi versus ICI alone (245 vs 100.5 days, p=0.002). On multivariate analysis, ICI+COXi associated with increased TTP (HR 0.36, 95% CI 0.2 to 0.66, p=0.001), adjusted for age, pretreatment NLR, and gender. For NSCLC patients, ICI+COXi also associated with increased TTP compared with ICI alone on multivariate analysis (HR 0.45; 95% CI 0.21 to 0.97; p=0.042) adjusted for age. ORR at 6 months was significantly higher in patients who received ICI+COXi compared with ICI alone in both melanoma (58.6% vs 19.2%, p=0.0005) and NSCLC (73.7% vs 33.3%, p=0.036) cohorts. In the melanoma cohort, high pretreatment NLR (>5) associated with decreased TTP (HR 3.21, 95% CI 1.64 to 6.3; p=0.0007); however, ICI+COXi significantly associated with increased TTP in high NLR (>5) patients (HR 0.08, 95% CI 0.03 to 0.25), but not in low NLR (≤5) patients (HR 0.65, 95% CI 0.32 to 1.32). Similar outcomes were found in an adjusted melanoma cohort after RECIST review.ConclusionsOur study suggests that COXi use concurrently with ICI significantly associated with longer TTP and improved ORR at 6 months in patients with metastatic melanoma and NSCLC compared with ICI alone. Furthermore, COXi use appears to reverse the negative prognostic effect of a high NLR by prolonging TTP in patients with melanoma.

show abstract

Predicting outcomes in patients with advanced non-small cell lung cancer enrolled in early phase immunotherapy trials

Cited by 31 publications

References 30 publications

Pretreatment Neutrophil-to-Lymphocyte Ratio (NLR) May Predict the Outcomes of Advanced Non-small-cell Lung Cancer (NSCLC) Patients Treated With Immune Checkpoint Inhibitors (ICIs)

Pretreatment Neutrophil-to-Lymphocyte Ratio (NLR) May Predict the Outcomes of Advanced Non-small-cell Lung Cancer (NSCLC) Patients Treated With Immune Checkpoint Inhibitors (ICIs)

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

Effect of cyclo-oxygenase inhibitor use during checkpoint blockade immunotherapy in patients with metastatic melanoma and non-small cell lung cancer

Contact Info

Product

Resources

About