Immune checkpoint inhibitor treatment in patients with oncogene-addicted non-small cell lung cancer (NSCLC): summary of a multidisciplinary round-table discussion

Berghoff, Anna Sophie; Bellosillo, Beatríz; Caux, Christophe; Langen, Adrianus De; Mazières, Julien; Normanno, Nicola; Preusser, Matthias; Provencio, Mariano; Rojo, Federico; Wolf, Jürgen; Zielinski, Christoph

doi:10.1136/esmoopen-2019-000498

Cited by 41 publications

(41 citation statements)

References 79 publications

(106 reference statements)

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“…Berghoff et al recently reviewed ICI treatment in patients with oncogene-addicted NSCLC (Berghoff et al 2019). They evaluated the efficacy of ICIs in NSCLC patients with wild-type EGFR and in patients with EGFR-mutated NSCLC in five clinical trials: CheckMate 057 (Borghaei et al 2015), KEYNOTE-010 (Herbst et al 2016), OAK (Rittmeyer et al 2017), POPLAR (Fehrenbacher et al 2016), and IMpower150 (Socinski et al 2018), and found that the survival benefits of treatment with an ICI tended to and December 2018, the 263 patients were adopted as the subjects of this study and divided into 4 groups based on their programmed death-ligand-1 (PD-L1) expression level and EGFR mutation status.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of anti-PD-1 antibodies in NSCLC patients with an EGFR mutation and high PD-L1 expression

Masuda¹,

Horinouchi²,

Tanaka³

et al. 2020

J Cancer Res Clin Oncol

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Introduction Several studies have demonstrated that non-small cell lung cancer patients (NSCLCs) harboring epidermal growth factor receptor (EGFR) mutations have poor clinical outcomes in response to treatment with programmed death-1 (PD-1) inhibitors. However, it remains unclear whether EGFR-mutated NSCLCs with a high programmed death-ligand-1 (PD-L1) expression (tumor proportion score ≥ 50%) respond to PD-1 inhibitors. Methods We retrospectively investigated the NSCLCs who had received PD-1 inhibitors between January 2016 and December 2018 to assess the efficacy of PD-1 inhibitors in patients with an EGFR mutation and high PD-L1 expression. Results There were 153 patients with a high PD-L1 expression level, and the median progression-free survival (mPFS) was 5.3 months [95% confidence interval (CI) 1.3-12.4 months] in the patients with EGFR mutations (n = 17) and 8.3 months (95% CI 6.0-11.7 months) in those with wild-type EGFR (n = 136; hazard ratio (HR) 1.62; 95% CI 0.83-2.87). Among the 110 patients in the low PD-L1 expression group, the mPFS was 1.6 months (95% CI 1.3-5.9 months) in the patients with EGFR mutations (n = 18) and 3.8 months (95% CI 2.5-5.9 months) in those with wild-type EGFR (n = 92; HR 2.59; 95% CI 1.48-4.31). The HR for PFS in the group with EGFR mutations and high PD-L1 expression was 0.97 (95% CI 0.56-1.59) compared to the group with wild-type EGFR and low PD-L1 expression. Conclusions PD-1 inhibitors can serve as one of the treatment options for NSCLCs with an EGFR mutation and high PD-L1 expression.

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Section: Discussionmentioning

confidence: 99%

Efficacy of anti-PD-1 antibodies in NSCLC patients with an EGFR mutation and high PD-L1 expression

Masuda¹,

Horinouchi²,

Tanaka³

et al. 2020

J Cancer Res Clin Oncol

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“…3,48 Conversely, tumours with oncogene addiction such as non-small cell lung cancer with ALK fusion or EGFR mutation have been shown to have lower TMB and lower likelihood of response to ICI in lung cancer. 61,62 While these findings require validation across tumour types and contexts, they raise the question of whether tumours with a single gene driver -such as iCCA with FGFR2 fusions -may harbour fewer tumour-associated antigens and consequently have lower response rates to ICI. Future subanalyses of ICI studies in CCA, according to tumour mutational status, are needed to confirm whether certain genetically defined subgroups are more or less likely to respond to ICI.…”

Section: Tumour Geneticsmentioning

confidence: 99%

Systemic therapies for intrahepatic cholangiocarcinoma

Kelley

Bridgewater

Gores

et al. 2020

Journal of Hepatology

274

206

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Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal hepatobiliary neoplasm whose incidence is increasing. Largely neglected for decades as a rare malignancy and frequently misdiagnosed as carcinoma of unknown primary, considerable clinical and investigative attention has recently been focused on iCCA worldwide. The established standard of care includes first-line (gemcitabine and cisplatin), second-line (FOLFOX) and adjuvant (capecitabine) systemic chemotherapy. Compared to hepatocellular carcinoma, iCCA is genetically distinct with several targetable genetic aberrations identified to date. Indeed, FGFR2 and NTRK fusions, and IDH1 and BRAF targetable mutations have been comprehensively characterised and clinical data is emerging on targeting these oncogenic drivers pharmacologically. Also, the role of immunotherapy has been examined and is an area of intense investigation. Herein, in a timely and topical manner, we will review these advances and highlight future directions of research.

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“…Despite promising advances in immunotherapy, the role of ICIs in oncogene-addicted NSCLC remains unclear and conflicting. The majority of data come from subgroup analyses with low number of patients, therefore the use of ICIs, when permitted by regulatory agencies, should only be considered when other available therapies, including standard EGFR-TKIs, fail (34).…”

Section: Immunotherapy In the Management Of Egfr-mutated Lung Cancermentioning

confidence: 99%

Targeting Immunometabolism Mediated by CD73 Pathway in EGFR-Mutated Non-small Cell Lung Cancer: A New Hope for Overcoming Immune Resistance

et al. 2020

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Despite the relevant antitumor efficacy of immunotherapy in advanced non-small cell lung cancer (NSCLC), the results in patients whose cancer harbors activating epidermal growth factor receptor (EGFR) mutations are disappointing. The biological mechanisms underlying immune escape and both unresponsiveness and resistance to immunotherapy in EGFR-mutant NSCLC patients have been partially investigated. To this regard, lung cancer immune escape largely involves high amounts of adenosine within the tumor milieu with broad immunosuppressive effects. Indeed, besides immune checkpoint receptors and their ligands, other mechanisms inducing immunosuppression and including adenosine produced by ecto-nucleotidases CD39 and CD73 contribute to lung tumorigenesis and progression. Here, we review the clinical results of immune checkpoint inhibitors in EGFR-mutant NSCLC, focusing on the dynamic immune composition of EGFR-mutant tumor microenvironment. The adenosine pathway-mediated dysregulation of energy metabolism in tumor microenvironment is suggested as a potential mechanism involved in the immune escape process. Finally, we report the strong rationale for planning strategies of combination therapy with immune checkpoints blockade and adenosine signaling inhibition to overcome immune escape and immunotherapy resistance in EGFR-mutated NSCLC.

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Immune checkpoint inhibitor treatment in patients with oncogene-addicted non-small cell lung cancer (NSCLC): summary of a multidisciplinary round-table discussion

Cited by 41 publications

References 79 publications

Efficacy of anti-PD-1 antibodies in NSCLC patients with an EGFR mutation and high PD-L1 expression

Efficacy of anti-PD-1 antibodies in NSCLC patients with an EGFR mutation and high PD-L1 expression

Systemic therapies for intrahepatic cholangiocarcinoma

Targeting Immunometabolism Mediated by CD73 Pathway in EGFR-Mutated Non-small Cell Lung Cancer: A New Hope for Overcoming Immune Resistance

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