Immunotherapy in advanced Non-Small Cell Lung Cancer patients with poor performance status: The role of clinical-pathological variables and inflammatory biomarkers

Lobefaro, Riccardo; Viscardi, Giuseppe; Liello, Raimondo Di; Massa, Giacomo; Iacovino, Maria Lucia; Sparano, Francesca; Corte, Carminia Maria Della; Ferrara, Roberto; Signorelli, Diego; Proto, Claudia; Prelaj, Arsela; Galli, Giulia; Toma, Alessandro De; Brambilla, Marta; Ganzinelli, Monica; Trevisan, Benedetta; Ciardiello, Fortunato; Braud, Filippo de; Garassino, Marina Chiara; Russo, Giuseppe Lo

doi:10.1016/j.lungcan.2020.12.027

Cited by 26 publications

(17 citation statements)

References 41 publications

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“…Most immunotherapy-related RCTs excluded patients with ECOG PS ≥ 2, so data on selecting an effective population for immunotherapy based on ECOG PS status are scarce. Two retrospective studies demonstrated that NSCLC patients with ECOG PS ≥ 2 were not suitable for immunotherapy (35,36), which is consistent with the results found in our study, though we only included 4 patients with PS = 2. The combination of radiotherapy and immunotherapy usually introduces synergistic treatment effects and increases the occurrence of the "abscopal effect" (37).…”

Section: Discussionsupporting

confidence: 90%

Association of Dynamic Changes in Peripheral Blood Indexes With Response to PD-1 Inhibitor-Based Combination Therapy and Survival Among Patients With Advanced Non-Small Cell Lung Cancer

et al. 2021

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BackgroundPD-1 inhibitors have been routinely used in the treatment of advanced non-small cell lung cancer (NSCLC), and have demonstrated to significantly improve survivorship when combining with other conventional therapies, such as chemotherapy and anti-angiogenesis therapy. PD-L1 is the most commonly used biomarker to select benefiting groups, while not all patients with high PD-L1 expression benefit from immunotherapy. Therefore, identifying other prognostic and predictive biomarkers, including peripheral blood indexes, is essential.MethodsWe retrospectively collected medical records and hematological data of 151 patients with advanced NSCLC treated with PD-1 inhibitor-based combination therapy in our hospital. The peripheral blood indexes of interest were NLR, PLR, PAR, Hb, LDH, CEA, and NSE. The association between peripheral blood indexes and treatment responses or survival outcomes was examined by multivariable logistic regression and Cox regression, respectively.ResultsThe decreased CEA at week 6 (OR = 4.209, 95%CI: 1.287-13.758) or 12 (OR = 7.267, 95%CI: 1.508-35.006) post-treatment was related to a higher disease control rate. The decrease or NLR at week 6 (OR = 3.081, 95%CI: 1.464-6.483) or 12 (OR = 3.304, 95%CI: 1.560-7.001) post-treatment, or CEA at week 12 post-treatment (OR = 2.469, 95%CI: 1.134-5.375), was associated with a higher objective response rate. Patients whose NLR (HR = 0.610, 95%CI: 0.411-0.907) or CEA (HR = 0.477, 95%CI: 0.320-0.710) decreased at week 6 post-treatment tended to have longer progression-free survival, and similar results were found in those with decreased NLR (HR = 0.587, 95%CI: 0.388-0.886) or CEA (HR = 0.406, 95%CI: 0.270-0.609) at week 12 post-treatment. Patients whose CEA (HR = 0.543, 95%CI: 0.339-0.871) or NSE (HR = 0.619, 95%CI: 0.386-0.994) decreased after 6 weeks post-treatment appeared to have longer overall survival, and the same was found for those whoseCEA (HR = 0.620, 95%CI: 0.390-0.986) or NSE (HR = 0.578, 95%CI: 0.353-0.947) was decreased at 12 weeks after treatment.ConclusionPost-treatment NLR, CEA and NSE changes are suggestive indicators for the prognosis of NSCLC patients after immunotherapy.

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Section: Discussionsupporting

confidence: 90%

Association of Dynamic Changes in Peripheral Blood Indexes With Response to PD-1 Inhibitor-Based Combination Therapy and Survival Among Patients With Advanced Non-Small Cell Lung Cancer

et al. 2021

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“…The efficacy endpoints in ECOG PS 0-1 patients were better than for ICIs plus anti-angiogenesis agents in previous studies (9,11,12). ECOG PS 2 and liver metastasis showed a poor response to immunotherapy, which was similar to other studies (10,23,26). It is noteworthy that prior anti-angiogenesis therapy may have affected the tumor response and mPFS of nivolumab plus rh-endostatin, but not the mOS.…”

Section: Discussionsupporting

confidence: 80%

Safety and efficacy of nivolumab plus recombinant human endostatin in previously treated advanced non-small-cell lung cancer

Lv¹,

Pei²,

Zhao³

et al. 2022

Transl Lung Cancer Res

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Background: Evidence of the efficacy of immune checkpoint inhibitors (ICIs) plus antiangiogenic drugs in previously treated patients with advanced non-small-cell lung cancer (NSCLC) is still insufficient, so we investigated the safety and efficacy of nivolumab plus recombinant human (rh)-endostatin in such patients.Methods: Patients without epithelial growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) targetable mutations in advanced NSCLC who did not respond to previous treatment were enrolled. Eligible patients received nivolumab (3 mg/kg, i.v. drip, day 1) every 2 weeks and rh-endostatin (210 mg, continuous i.v. infusion for 168 h) every 4 weeks until disease progression or discontinuation. The primary endpoint was the objective response rate (ORR). The secondary endpoints included disease control rate (DCR), duration of response (DOR), clinical benefit response rate (CBR), progression-free survival (PFS), overall survival (OS) and safety.Results: A total of 34 patients received a median of 4 cycles of therapy. In all, 14 patients achieved confirmed partial response (PR) with an ORR of 41.2% [14/34; 95% confidence interval (CI): 23.7-58.6%],

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“…It is hypothesized that higher mutation burden resulting from smoking improves the efficacy of immunotherapy [ 23 ] . Additionally, data from two Italian centers confirm poor PS was associated with reduced efficacy of immunotherapy and remained the most powerful independent prognostic factor for NSCLC [ 24 ] . These findings provide evidence for the potential risk of systemic progression after ICIs failure for patients who have no smoking history and poor performance status.…”

Section: Discussionmentioning

confidence: 99%

Favorable clinical outcomes of checkpoint inhibitor-based combinations after progression with immunotherapy in advanced non-small cell lung cancer

Yu¹,

Chu²,

Wu³

et al. 2021

CDR

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Aim: Immune checkpoint inhibitors (ICIs) have dramatically changed the treatment paradigm in patients with nonsmall-cell lung cancer (NSCLC). However, progression patterns with immunotherapy are currently unclear and therapeutic options beyond resistance remain challenging. Methods:We reviewed advanced NSCLC patients between January 2016 and December 2019 who were treated with anti-PD-1/PD-L1 inhibitors in our center and identified those who developed disease progression. Later-line treatment strategies were collected and objective response rate, progression-free survival (PFS), and overall survival (OS) were assessed.Results: Of the 118 patients, 46 (39.0%) showed oligoprogression and 72 (61.0%) showed systemic progression. No difference in progression patterns was observed between monotherapy and combination therapy. Systemic progression was strongly associated with never-smokers (51.4% vs. 21.7%, P = 0.001) and ECOG PS = 2 (13.9% vs. 2.2%, P = 0.048) at baseline. The distribution of progression sites was roughly similar between oligoprogression and systemic progression, and the most commonly affected anatomic site was lung (66.9%), followed by bone Conclusion: Systemic progression occurs more frequently among NSCLC patients receiving ICIs. Checkpoint inhibitor-based combinations show favorable outcomes as subsequent treatment strategies after the failure of previous ICIs treatment.

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Immunotherapy in advanced Non-Small Cell Lung Cancer patients with poor performance status: The role of clinical-pathological variables and inflammatory biomarkers

Cited by 26 publications

References 41 publications

Association of Dynamic Changes in Peripheral Blood Indexes With Response to PD-1 Inhibitor-Based Combination Therapy and Survival Among Patients With Advanced Non-Small Cell Lung Cancer

Association of Dynamic Changes in Peripheral Blood Indexes With Response to PD-1 Inhibitor-Based Combination Therapy and Survival Among Patients With Advanced Non-Small Cell Lung Cancer

Safety and efficacy of nivolumab plus recombinant human endostatin in previously treated advanced non-small-cell lung cancer

Favorable clinical outcomes of checkpoint inhibitor-based combinations after progression with immunotherapy in advanced non-small cell lung cancer

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