Immune-checkpoint inhibitors in non-small cell lung cancer: A tool to improve patients’ selection

Banna, Giuseppe Luigi; Passiglia, Francesco; Colonese, Francesca; Canova, Stefania; Menis, Jessica; Addeo, Alfredo; Russo, Antonio; Cortinovis, Diego

doi:10.1016/j.critrevonc.2018.06.016

Cited by 45 publications

(32 citation statements)

References 126 publications

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“…TMB in particular, has been associated with a favorable response to Nivolumab in NSCLC patients receiving this treatment as frontline therapy. Nevertheless, next generation sequencing, which allows for TMB analysis, cannot be considered as a common practice (14,55).…”

Section: Discussionmentioning

confidence: 99%

Early blood rise in auto‑antibodies to nuclear and smooth muscle antigens is predictive of prolonged survival and autoimmunity in metastatic‑non‑small cell lung cancer patients treated with PD‑1 immune‑check point blockade by nivolumab

Giannicola

D’Arrigo²,

Botta

et al. 2019

mol clin onc

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Immune-checkpoint blockade by Nivolumab, a human monoclonal antibody to programmed cell death receptor-1, is an emerging treatment for metastatic non-small cell lung cancer (mNSCLC). In order to prolong patient survival, this treatment requires a continuous cross-priming of tumor derived-antigens to supply fresh tumor-specific immune-effectors; a phenomenon that may also trigger auto-immune-related adverse events (irAEs). The present study therefore investigated the prognostic value of multiple autoimmunity-associated parameters in patients with mNSCLC who were undergoing Nivolumab treatment. This retrospective study included 92 mNSCLC patients who received salvage therapy with Nivolumab (3 mg/kg, biweekly) between September 2015 and June 2018. Log-rank test, Mantel-Cox and McPherson analyses were conducted to correlate patient progression-free survival (PFS) and overall survival (OS) with different parameters including blood cell counts, serum inflammatory markers and auto-antibodies (AAbs). A median PFS and OS of 10 [inter-quartile range (IQR): 5.8-14.2] and 16 [IQR: 6.2-25.8] months, respectively, were recorded, which did not correlated with age, histology or the number of previous chemotherapy lines. Male gender, the type of therapeutic regimens received prior to Nivolumab, and the occurrence of irAEs were revealed to be positive predictors of prolonged survival (P<0.05). Early detection (within 30 days) of >1AAbs among anti-nuclear antigens (ANAs), extractable nuclear antigens (ENAs) and anti-smooth cell antigens (ASMAs) correlated with prolonged PFS [hazard ratio (HR)= 0.23; 95% confidence interval (

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Section: Discussionmentioning

confidence: 99%

Early blood rise in auto‑antibodies to nuclear and smooth muscle antigens is predictive of prolonged survival and autoimmunity in metastatic‑non‑small cell lung cancer patients treated with PD‑1 immune‑check point blockade by nivolumab

Giannicola

D’Arrigo²,

Botta

et al. 2019

mol clin onc

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“…These drugs have significantly improved the prognosis of many cancer types. For example, 5-year survival for advanced non-small-cell lung cancer (NSCLC) has increased from 5% to 16%–25%,3–5 and for melanoma, from 22% to 34%–41% 6. While immune-checkpoint inhibitors (ICI) have revolutionised the treatment of many cancer types, the majority of patients still progress 7…”

Section: Introductionmentioning

confidence: 99%

New emerging targets in cancer immunotherapy: the role of TIM3

2019

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Currently, the programmed death-1/programmed death ligand-1 and the cytotoxic T-lymphocyte-associated protein 4 are the two commonly targeted immune-checkpoint inhibition pathways. These drugs have significantly improved the prognosis of many cancer types. While immune-checkpoint inhibitors have revolutionised the treatment of many cancer types, the majority of patients still progress. Several treatment strategies have been pursued to improve current results. One approach is to combine two checkpoint inhibitors, currently with promising results in melanoma, renal cell carcinoma and a subset of non-small-cell lung cancer patients. The identification of new checkpoint targets could allow the field of immuno-oncology to evolve further. We will discuss one of the most promising immune-checkpoint targets currently under investigation, the T-cell immunoglobulin and mucin domain-3.

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“…Subsequently, in metastatic NSCLC patients with PD-L1 expression of at least 50% on tumor cells, upfront pembrolizumab improved median progression-free survival (PFS) and overall survival (OS) compared to standard platinum-based chemotherapy (9). However, patients with a tumor proportion score (TPS) of 50% or greater represent only 20-30% of those with NSCLC (10). To enhance the immune response through PD-1 inhibition, several studies have combined the potential immunogenic effects of cytotoxic chemotherapy with immune checkpoint inhibitors (ICPI).…”

Section: Introductionmentioning

confidence: 99%

Chemotherapy in combination with immune checkpoint inhibitors for the first-line treatment of patients with advanced non-small cell lung cancer: A systematic review and literature-based meta-analysis.

Addeo

Banna

Metro

et al. 2019

JCO

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e20565 Background: Checkpoint inhibitors plus platinum-based chemotherapy have shown superiority compared to chemotherapy alone as first-line therapy in advanced non–small cell lung carcinoma (NSCLC),To evaluate the relative benefit in term of Overall Survival (OS) and Progression-free Survival (PFS) of checkpoint inhibitors plus chemotherapy versus chemotherapy alone, overall and in subgroups defined by PDL1 expression we have performed a meta-analysis Methods: This meta-analysis searched PubMed and checked references of the selected English language articles to identify further eligible trials. Furthermore, proceedings of the main International meetings (American Society of Clinical Oncology [ASCO] annual meeting, European Society of Medical Oncology [ESMO] annual meeting, International Association for the Study of Lung Cancer [IASLC] World Conference on Lung Cancer), were searched from 2010 onwards for relevant abstracts. Data collection for this study took place from October 1 to October 24, 2018. Results: In total, 8 trials involving 4646 patients with advanced NSCLC, 3.314 (71%) and 1.332 (29%) with a non-squamous and squamous histology, respectively, were included in this meta-analysis. Four trials used atezolizumab, 3 pembrolizumab and 1 nivolumab, accounting for 2.985 (64%), 1.298 (28%) and 363 (8%) of patients, respectively. Checkpoint inhibitors plus chemotherapy were associated with prolonged OS, compared with chemotherapy in the ITT population (HR, 0.74; 95% CI, 0.64-0.87; p = 0.0002, with significant heterogeneity among trials). Within the PDL1 low group (1-49) there was a significant heterogeneity (p = 0.06) between type of drug and efficacy: the combination of chemotherapy plus pembrolizumab showed an OS benefit (HR, 0.56; 95% CI, 0.40-0.78; P< .00007) unlike the atezolizumab backbone trials (HR, 0.92; 95% CI, 0.62-1.37; P< 0.69). However, checkpoint inhibitors plus chemotherapy were associated with prolonged PFS in the ITT (HR, 0.61; 95% CI, 0.56-0.66; P < 0.00001) and across PDL1 subgroups. Conclusions: Checkpoint inhibitors plus chemotherapy compared with chemotherapy, are associated with significantly prolonged OS and PFS in first-line therapy in NSCLC. In the low PDL1 subgroups the benefit was statistically significant only in the pembrolizumab backbone trials.

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Immune-checkpoint inhibitors in non-small cell lung cancer: A tool to improve patients’ selection

Cited by 45 publications

References 126 publications

Early blood rise in auto‑antibodies to nuclear and smooth muscle antigens is predictive of prolonged survival and autoimmunity in metastatic‑non‑small cell lung cancer patients treated with PD‑1 immune‑check point blockade by nivolumab

Early blood rise in auto‑antibodies to nuclear and smooth muscle antigens is predictive of prolonged survival and autoimmunity in metastatic‑non‑small cell lung cancer patients treated with PD‑1 immune‑check point blockade by nivolumab

New emerging targets in cancer immunotherapy: the role of TIM3

Chemotherapy in combination with immune checkpoint inhibitors for the first-line treatment of patients with advanced non-small cell lung cancer: A systematic review and literature-based meta-analysis.

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