Predictive and prognostic clinical and pathological factors of nivolumab efficacy in non-small-cell lung cancer patients

Garde-Noguera, Javier; Martín-Martorell, Paloma; Julián, María De; Perez-Altozano, J.; Coloma, Carmen Salvador; García-Sánchez, José; Insa, Amelia; Martín, M. Segura; Mielgo-Rubio, Xabier; Marin-Liebana, S.; Cordellat, A. Blasco; Blasco-Molla, S.; Gironés, Regina; Marquez-Medina, Diego; Aparisi, Francisco; Cerda, M. C. Bas; Macia-Escalante, S.; Sánchez, Alfredo; Juan, Óscar

doi:10.1007/s12094-017-1829-5

Cited by 48 publications

(41 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our study of the 67NR breast cancer cell line, tumors growing in the lungs were only slightly responsive to trimAb immunotherapy and not responsive to αPD‐1/αCTLA4 whereas tumors growing in the MFP could be eradicated by these therapies. In non‐small‐cell lung cancer (NSCLC), response to nivolumab (αPD‐1) was reduced in patients with secondary lung metastasis in one study, and no change in other studies . Complete response rates of lung metastases in melanoma are increased to single agent αPD‐1 than at other metastatic sites in some cases, but not others, and are not associated with responses to αPD‐1/CTLA4 .…”

Section: Discussionmentioning

confidence: 99%

“…A recently revealed clinical trend shows some association with liver metastases and reduced responses to αPD‐1 across cancer types in melanoma, urothelial cancer, TNBC and NSCLC . However, there are some conflicting results with some studies reporting no associations with liver metastases . Furthermore, data indicating a poor response in patients with liver tumors could be confounded with the aggressive nature of tumors that metastasise to the liver.…”

Section: Discussionmentioning

confidence: 99%

“…In non-small-cell lung cancer (NSCLC), response to nivolumab (aPD-1) was reduced in patients with secondary lung metastasis in one study, 21 and no change in other studies. 17,23 Complete response rates of lung metastases in melanoma are increased to single agent aPD-1 than at other metastatic sites in some cases, [13][14][15][16] but not others, 17,18 and are not associated with responses to aPD-1/CTLA4. 18 There is no observed association of lung metastases with response to pembrolizumab (aPD-1) in triple-negative breast cancer (TNBC) patients.…”

Section: Discussionmentioning

confidence: 99%

“…Evidence has recently emerged for the tumor location influencing the response of human tumors to immunotherapies, particularly to αPD‐1 and αPD‐1/αCTLA4 . In particular, retrospective analysis has revealed reduced responses to checkpoint blockade in tumors in certain metastatic sites compared with primary tumors in melanoma, non‐small‐cell lung cancer (NSCLC), urothelial cancer and triple‐negative breast cancer (TNBC) . Due to the complexity of tumors at different anatomical sites, including tumor genetic heterogeneity, the tissue‐specific impact on therapy responses in human tumors is yet to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

“…[10][11][12] In particular, retrospective analysis has revealed reduced responses to checkpoint blockade in tumors in certain metastatic sites compared with primary tumors in melanoma, non-small-cell lung cancer (NSCLC), urothelial cancer and triple-negative breast cancer (TNBC). 11,[13][14][15][16][17][18][19][20][21][22][23][24][25] Due to the complexity of tumors at different anatomical sites, including tumor genetic heterogeneity, the tissue-specific impact on therapy responses in human tumors is yet to be elucidated. Previously, we and others used genetically identical murine tumor lines to eliminate genetic heterogeneity and have shown differences in the TME composition and therapy responses of tumors growing in different anatomical sites in murine models of cancer.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Tissue‐specific tumor microenvironments influence responses to immunotherapies

et al. 2019

View full text Add to dashboard Cite

Objectives Investigation of variable response rates to cancer immunotherapies has exposed the immunosuppressive tumor microenvironment (TME) as a limiting factor of therapeutic efficacy. A determinant of TME composition is the tumor location, and clinical data have revealed associations between certain metastatic sites and reduced responses. Preclinical models to study tissue‐specific TMEs have eliminated genetic heterogeneity, but have investigated models with limited clinical relevance. Methods We investigated the TMEs of tumors at clinically relevant sites of metastasis (liver and lungs) and their impact on αPD‐1/αCTLA4 and trimAb (αDR5, α4‐1BB, αCD40) therapy responses in the 67NR mouse breast cancer and Renca mouse kidney cancer models. Results Tumors grown in the lungs were resistant to both therapies whereas the same tumor lines growing in the mammary fat pad (MFP), liver or subcutaneously could be completely eradicated, despite greater tumor burden. Assessment of tumor cells and drug delivery in 67NR lung or MFP tumors revealed no differences and prompted investigation into the immune TME. Lung tumors had a more immunosuppressive TME with increased myeloid‐derived suppressor cell infiltration, decreased T cell infiltration and activation, and decreased NK cell activation. Depletion of various immune cell subsets indicated an equivalent role for NK cells and CD8+ T cells in lung tumour control. Thus, targeting T cells with αPD‐1/αCTLA4 or trimAb was not sufficient to elicit a robust antitumor response in lung tumors. Conclusion Taken together, these data demonstrate that tissue‐specific TMEs influence immunotherapy responses and highlight the importance in defining tissue‐specific response patterns in patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Tissue‐specific tumor microenvironments influence responses to immunotherapies

et al. 2019

View full text Add to dashboard Cite

show abstract

Predictive factors for progression‐free survival in non‐small cell lung cancer patients receiving nivolumab based on performance status

et al. 2019

View full text Add to dashboard Cite

Background Nivolumab has promising efficacy for the treatment of non‐small cell lung cancer (NSCLC). Various predictive factors for nivolumab response in those with NSCLC have been reported, including performance status (PS). The objective of this retrospective study was to determine the predictive factors for nivolumab response in those with NSCLC with good PS and those with poor PS. Methods We retrospectively collected pretreatment clinical data of 296 consecutive patients with NSCLC treated with nivolumab. We investigated the relationship between progression‐free survival (PFS) and patient characteristics and analyzed predictive factors associated with good PS (PS 0‐1) or poor PS (PS 2‐4). Results The median age of patients was 70 years; 206 patients were male, and 224 were classified as having good PS (PS 0‐1). The median PFS was 3.0 months, 3.7 months, and 1.2 months for all patients, patients with good PS, and patients with poor PS respectively. Multivariate analysis showed that never smoking (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.15‐2.75), high C‐reactive protein (CRP) (HR, 1.39; 95% CI, 1.00‐1.93), liver metastasis (HR, 1.95; 95% CI, 1.24‐3.07), pleural effusion (HR, 1.45; 95% CI, 1.06‐2.00), and steroid use (HR, 2.85; 95% CI, 1.65‐4.94) were associated with significantly shorter PFS in patients with good PS. A high advanced lung cancer inflammation index (ALI) was significantly associated with longer PFS in patients with poor PS (HR, 0.24; 95% CI, 0.08‐0.79). Conclusions In patients with NSCLC treated with nivolumab, the factors found to be predictive of shorter PFS in patients with good PS were never smoking, high CRP, liver metastasis, pleural effusion, and steroid administration, whereas high ALI was predictive of longer PFS in patients with poor PS.

show abstract

Real‐world data prognostic model of overall survival in patients with advanced NSCLC receiving anti‐PD‐1/PD‐L1 immune checkpoint inhibitors as second‐line monotherapy

Azcona¹,

Machado

Girish³

et al. 2022

Cancer Reports

View full text Add to dashboard Cite

Background and aim The objective of this retrospective, observational, noninterventional cohort study was to investigate prognostic factors of overall survival (OS) in patients with advanced non‐small cell lung cancer (aNSCLC) and to develop a novel prognostic model. Methods A total of 4049 patients with aNSCLC diagnosed between January 2011 and February 2020 who received atezolizumab, nivolumab, or pembrolizumab as second‐line monotherapy were selected from a real‐world deidentified database to build the cohort. Patients could not have received first‐line treatment with clinical study drug(s) nor immune checkpoint inhibitors including anti‐programmed cell death 1 (PD‐1)/programmed death‐ligand 1 (PD‐L1), and anti‐cytotoxic T‐lymphocyte‐associated protein 4 therapies. Results Patients had a median age of 69 years; 45% were female, 75% White, 70% had stage IV at initial diagnosis, and 70% had nonsquamous histology. A Cox proportional hazards model with lasso regularization was used to build a prognostic model for OS using 18 baseline demographic and clinical factors based on the real‐world data cohort. The risk‐increasing prognostic factors were abnormally low albumin and chloride levels, Eastern Cooperative Oncology Group performance status score ≥ 2, and abnormally high levels of alkaline phosphatase and white blood cells. The risk‐decreasing prognostic factors were PD‐L1 positivity, longer time from advanced diagnosis to start of first‐line therapy, and higher systolic blood pressure. The performance of the model was validated using data from the OAK trial, and the c‐index for the OAK trial validation cohort was 0.65 and 0.67 for the real‐world data cohort. Conclusions Based on baseline demographic and clinical factors from a real‐world setting, this prognostic model was developed to discriminate the risk of death in patients with aNSCLC treated with checkpoint inhibitors as second‐line monotherapy, and it performed well in the real‐world data and clinical trial cohorts.

show abstract

Predictive and prognostic clinical and pathological factors of nivolumab efficacy in non-small-cell lung cancer patients

Abstract: Poor PS, short period of time since the previous treatment, and more than one metastatic location were associated with poorer prognostic.

Cited by 48 publications

References 14 publications

Tissue‐specific tumor microenvironments influence responses to immunotherapies

Tissue‐specific tumor microenvironments influence responses to immunotherapies

Predictive factors for progression‐free survival in non‐small cell lung cancer patients receiving nivolumab based on performance status

Real‐world data prognostic model of overall survival in patients with advanced NSCLC receiving anti‐PD‐1/PD‐L1 immune checkpoint inhibitors as second‐line monotherapy

Contact Info

Product

Resources

About