Immunotherapy for the First-Line Treatment of Patients with Metastatic Non–Small Cell Lung Cancer

Martı́nez, Pablo; Peters, Solange; Stammers, Timothy A.; Soria, Jean‐Charles

doi:10.1158/1078-0432.ccr-18-3904

Cited by 69 publications

(47 citation statements)

References 43 publications

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“…T‐cell exhaustion due to binding of PD‐1 and PD‐L1 induces immune evasion of cancer cells from anti‐cancer immune responses . The percentage of PD‐L1‐positivity in cancer cells, named the tumor proportion score (TPS), is also considered a predictive biomarker for anti‐PD‐1/PD‐L1 therapy in lung cancer .…”

Section: Introductionmentioning

confidence: 99%

Accurate expression of PD‐L1/L2 in lung adenocarcinoma cells: A retrospective study by double immunohistochemistry

et al. 2019

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The percentage of programmed death ligand 1 (PD‐L1) positivity in cancer cells, named as the tumor proportion score, is considered to be a predictive biomarker for anti‐PD‐1/PD‐L1 therapy in lung cancer. PD‐L1 is expressed on not only cancer cells but also on immune cells, including macrophages. Although previous studies related to PD‐L1/2 expression in cancer tissues have been generally based on single immunohistochemistry (IHC), in the present study, we attempted to evaluate accurate PD‐L1/2 expression in cancer cells in lung adenocarcinoma cells using double IHC to also evaluate macrophages. Of the 231 patients, PD‐L1 expression was negative in 169 patients (73.2%), 1%‐49% positive in 47 patients (20.3%), and ≥50% positive in 15 patients (6.5%). Interestingly, PD‐L1 positivity was decreased when using double IHC compared with the estimation by single IHC. High PD‐L1 expression was associated with high‐grade cancer cells and in higher stage cancer. PD‐L2 was negative in 109 patients (47.2%), 1%‐49% positive in 50 patients (21.6%), and ≥50% positive in 72 patients (31.2%). The number of PD‐L2‐positive patients was increased in cases that had an epidermal growth factor receptor (EGFR) mutation and in lower stage cancer. Thirty‐five patients (15.2%) were positive for both PD‐L1 and PD‐L2, whereas 81 patients (35.1%) were negative for both PD‐L1 and PD‐L2. Log‐rank analysis showed that progression‐free survival and overall survival were significantly the longest in the PD‐L1‐negative and PD‐L2‐positive groups (P < .0001 and P = .0120). We observed lower PD‐L1 or PD‐L2 expression in lung adenocarcinoma than previously reported. Double IHC for macrophages may help clinicians to evaluate PD‐L1 or PD‐L2 expression specifically in cancer cells.

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Section: Introductionmentioning

confidence: 99%

Accurate expression of PD‐L1/L2 in lung adenocarcinoma cells: A retrospective study by double immunohistochemistry

et al. 2019

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“…Four ICIs that targeting PD-1 or PD-L1 have been approved by the U.S. Food and Drug Administration (FDA) for treatment in patients with non-small cell lung cancer (NSCLC) [12]. Furthermore, a large amount of clinical research had demonstrated that immunotherapy alone or in combination with chemotherapy could be used for rst-line treatment of patients with metastatic lung cancer [13][14][15][16]. It was reported that patients with higher PD-L1 expression had better outcomes compared to patients with lower or no PD-L1 expression using the anti-PD-L1 antibody clone 22C3 [17].…”

Section: Introductionmentioning

confidence: 99%

Integrative modeling of multi-omics data for predicting tumor mutation burden in lung cancer patients

Chen

Wang

et al. 2020

Preprint

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Background Immunotherapy has been widely used in the treatment of lung cancer, and one of the most effective biomarker for the prognosis of immunotherapy currently is tumor mutation burden (TMB). Although whole-exome sequencing (WES) could be utilized to assess TMB, several problems prevent its routine clinical application. Methods To develop a simplified TMB prediction model, patients with lung adenocarcinoma (LUAD) in The Cancer Genome Atlas (TCGA) were randomly split into training and validation cohorts, and categorized into TMB-high (TMB-H) and TMB-low (TMB-L) groups respectively. Results Based on the 610 differentially expressed genes, 50 differentially expressed miRNAs and 58 differentially methylated CpG sites between TMB-H and TMB-L patients, we constructed 4 predictive signatures and established TMB prediction model through machine learning methods that integrating the expression or methylation profiles of 7 genes, 7 miRNAs and 6 CpG sites. The multi-omics model exhibited excellent performance in predicting TMB with the area under curve (AUC) of 0.911 in the training cohort and 0.859 in the validation cohort. Besides, the significant correlation between the multi-omics model score and TMB was observed. Conclusions In summary, we developed a prognostic TMB prediction model by integrating multi-omics data in patients with LUAD, which might facilitate the further development of quantitative real time-polymerase chain reaction (qRT-PCR) based TMB detection assay.

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“…The non-small cell lung cancer (NSCLC) treatment landscape has completely changed with the coming of age of immunotherapy. The past decade has seen great advances in the treatment of patients with advanced lung cancer, with the first clinically relevant improvements in overall survival (OS) occurring in the later lines of treatment followed by significant advances in the first-line setting that have upended the treatment algorithm [1].…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, several immunotherapy trials reported in 2017 and 2018 transformed the first-line treatment of metastatic NSCLC [1]. The preferred firstline treatment option for patients without targetable mutations is now an immunotherapy-based regimen alone or in combination with chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

“…The new therapeutic scenario that results from great advances in the standard of care, although having the potential to bring the best outcomes to patients for upfront treatment, does not address the best treatment to administer upon progressive disease. There is a need to optimize the sequential treatment of currently available regimens to further improve the survival outcome of patients with advanced wild-type lung adenocarcinoma [1].…”

Section: Introductionmentioning

confidence: 99%

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Treatment options beyond immunotherapy in patients with wild-type lung adenocarcinoma: a Delphi consensus

et al. 2019

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Purpose Immunotherapy-based approaches are standard first-line treatments for advanced/metastatic lung cancer or for chemoradiotherapy consolidation in locally advanced disease. Uncertainty on how to treat patients at disease progression prompted us to develop a consensus document on post-immunotherapy options in Spain for patients with advanced wildtype lung adenocarcinoma. Methods After extensive literature review, a 5-member scientific committee generated 33 statements in 4 domains: general aspects (n = 4); post-durvalumab in locally advanced disease (n = 6); post-first-line immunotherapy ± chemotherapy in advanced/metastatic disease (n = 11); and post-first-line platinum-based chemotherapy in advanced/metastatic disease (n = 12). A panel of 26 lung cancer experts completed 2 Delphi iterations through an online platform rating their degree of agreement/disagreement (first-round scale 1-5 and second-round scale 1-4, 1 = strongly disagree, 4/5 = strongly agree) for each statement. Second-round consensus: ≥ 70% of responses were in categories 1/2 (disagreement) or 3/4 (agreement). Results Consensus was reached for 2/33 statements in the first Delphi round and in 29/31 statements in the second round. Important variables informing treatment at disease progression with an immunotherapy-based treatment include: disease aggressiveness, previous treatment, accumulated toxicity, progression-free interval, PD-L1 expression, and tumour mutational burden. A platinum-based chemotherapy should follow a first-line immunotherapy treatment without chemotherapy. Treatment with docetaxel + nintedanib may be appropriate post-durvalumab in refractory patients or following progression to first-line chemotherapy + immunotherapy, or second-line chemotherapy after first-line immunotherapy, or first-line chemotherapy in some patients with low/negative PD-L1 expression, or second-line immunotherapy after first-line chemotherapy. Conclusions To support decision making following progression to immunotherapy-based treatment in patients with advanced wild-type lung adenocarcinoma, a consensus document has been developed.

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Immunotherapy for the First-Line Treatment of Patients with Metastatic Non–Small Cell Lung Cancer

Cited by 69 publications

References 43 publications

Accurate expression of PD‐L1/L2 in lung adenocarcinoma cells: A retrospective study by double immunohistochemistry

Accurate expression of PD‐L1/L2 in lung adenocarcinoma cells: A retrospective study by double immunohistochemistry

Integrative modeling of multi-omics data for predicting tumor mutation burden in lung cancer patients

Treatment options beyond immunotherapy in patients with wild-type lung adenocarcinoma: a Delphi consensus

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