Hyper‐progressive disease after immune checkpoint inhibitor in <scp>SMARCA4</scp>‐deficient small‐cell lung carcinoma

Chiba, Yosuke; Kawanami, Toshinori; Yamasaki, Kei; Uchimura, Keigo; Matsuyama, Atsuji; Yatera, Kazuhiro

doi:10.1002/rcr2.667

Cited by 12 publications

(10 citation statements)

References 6 publications

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“…Notably, there was one previous report that showed that PD-1 inhibitor was effective for a SMARCA4 deficient NSCLC patient with a high TMB and PD-L1 not highly expressed [9]. However, there was another study that reported hyperprogressive disease was obtained after immune checkpoint inhibitor treatment in SMARCA4 deficient SCLC [10].…”

Section: Discussionmentioning

confidence: 99%

Extremely Rapid Response to Pembrolizumab in a SMARCA4 Mutant PD-L1 Highly Expressive Advanced Lung Adenocarcinoma: A Case Report

Liu¹,

Zhu²,

Pan³

2021

SCR

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SMARCA4 mutant non-small cell lung cancer (SMARCA4m-NSCLC) has a poor prognosis owing to rapid growth. Effective treatments for SMARCA4m-NSCLC have not yet been established. Recently, many preclinical studies support the hypothesis that SMARCA4m-NSCLC may be vulnerable to immune checkpoint inhibitors. Here, we report a patient with programmed death-ligand1 (PD-L1) highly expressive SMARCA4m-NSCLC who showed an extremely rapid and long-term response to pembrolizumab. He was referred to our hospital for a mass of the right lung. Positron emission tomography-computed tomography showed right lung tumor, hilar, mediastinal and bone metastases. Pathological and immunohistochemical results showed it was a lung adenocarcinoma and revealed the tumor proportion score of PD-L1 was 80%. SMARCA4 and K-RAS genes were co-mutations. BRG1 protein expression was negative. Subsequently, pembrolizumab treatment as the first line of therapy was commenced for the patient. With only one dose, pembrolizumab significantly inhibited tumor growth and a partial response was obtained. To date, pembrolizumab treatment has been continued for about 29 months. Severe immune-related adverse events were not observed. Our case showed that an extremely rapid and long-term response can be achieved with pembrolizumab for PD-L1 highly expressive SMARCA4m-NSCLC. Immune checkpoint inhibitors treatment may be a promising strategy for PD-L1 positive SMARCA4m-NSCLC.

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Section: Discussionmentioning

confidence: 99%

Extremely Rapid Response to Pembrolizumab in a SMARCA4 Mutant PD-L1 Highly Expressive Advanced Lung Adenocarcinoma: A Case Report

Liu¹,

Zhu²,

Pan³

2021

SCR

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“…A few therapeutic molecules targeting these genomic alterations are under development, most are being tested in vitro but some are also being evaluated in clinical trials. ICIs have been found to be efficacious in patients with SMARCA4 mutated or rearranged tumors 138,139 . However, cases of hyper progression after administration of ICIs have also been reported in these tumors 139 .…”

Section: Other Gene Fusions In Nsclcmentioning

confidence: 99%

“…ICIs have been found to be efficacious in patients with SMARCA4 mutated or rearranged tumors 138,139 . However, cases of hyper progression after administration of ICIs have also been reported in these tumors 139 . The morphological and phenotypical characteristics can sometimes point to the diagnosis, since these cancers can contain rhabdoid cells or even poorly differentiated cells associated with islets of epidermoid cells 135 .…”

Section: Other Gene Fusions In Nsclcmentioning

confidence: 99%

“…138,139 However, cases of hyper progression after administration of ICIs have also been reported in these tumors. 139 The morphological and phenotypical characteristics can sometimes point to the diagnosis, since these cancers can contain rhabdoid cells or even poorly differentiated cells associated with islets of epidermoid cells. 135 One of the key diagnostic elements is the absence of expression in the majority of cases of TTF1 by tumor cells.…”

Section: Other Gene Fusions In Nsclcmentioning

confidence: 99%

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Fusion‐positive non‐small cell lung carcinoma: Biological principles, clinical practice, and diagnostic implications

Kazdal

Hofman

Christopoulos

et al. 2022

Genes Chromosomes & Cancer

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Based on superior efficacy and tolerability, targeted therapy is currently preferred over chemotherapy and/or immunotherapy for actionable gene fusions that occur in late‐stage non‐small cell lung carcinoma (NSCLC). Consequently, current clinical practice guidelines mandate testing for ALK, ROS1, NTRK, and RET gene fusions in all patients with newly diagnosed advanced non‐squamous NSCLC (NS‐NSCLC). Gene fusions can be detected using different approaches, but today RNA next‐generation sequencing (NGS) or combined DNA/RNA NGS is the method of choice. The discovery of other gene fusions (involving, eg, NRG1, NUT, FGFR1, FGFR2, MET, BRAF, EGFR, SMARC fusions) and their partners has increased progressively in recent years, leading to the development of new and promising therapies and mandating the development and implementation of comprehensive detection methods. The purpose of this review is to focus on recent data concerning the main gene fusions identified in NSCLC, followed by the discussion of major challenges in this domain.

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“…ICIs have been found to be efficacious in patients with SMARCA4-mutated tumors [267][268][269]. However, cases of hyper progression of tumors after administration of ICIs have been reported, too [270].…”

Section: Smarca4 Mutationsmentioning

confidence: 99%

What Is New in Biomarker Testing at Diagnosis of Advanced Non-Squamous Non-Small Cell Lung Carcinoma? Implications for Cytology and Liquid Biopsy

Hofman

2021

JMP

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The discovery and clinical validation of biomarkers predictive of the response of non-squamous non-small-cell lung carcinomas (NS-NSCLC) to therapeutic strategies continue to provide new data. The evaluation of novel treatments is based on molecular analyses aimed at determining their efficacy. These tests are increasing in number, but the tissue specimens are smaller and smaller and/or can have few tumor cells. Indeed, in addition to tissue samples, complementary cytological and/or blood samples can also give access to these biomarkers. To date, it is recommended and necessary to look for the status of five genomic molecular biomarkers (EGFR, ALK, ROS1, BRAFV600, NTRK) and of a protein biomarker (PD-L1). However, the short- and more or less long-term emergence of new targeted treatments of genomic alterations on RET and MET, but also on others’ genomic alteration, notably on KRAS, HER2, NRG1, SMARCA4, and NUT, have made cellular and blood samples essential for molecular testing. The aim of this review is to present the interest in using cytological and/or liquid biopsies as complementary biological material, or as an alternative to tissue specimens, for detection at diagnosis of new predictive biomarkers of NS-NSCLC.

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Hyper‐progressive disease after immune checkpoint inhibitor in SMARCA4‐deficient small‐cell lung carcinoma

Cited by 12 publications

References 6 publications

Extremely Rapid Response to Pembrolizumab in a SMARCA4 Mutant PD-L1 Highly Expressive Advanced Lung Adenocarcinoma: A Case Report

Extremely Rapid Response to Pembrolizumab in a SMARCA4 Mutant PD-L1 Highly Expressive Advanced Lung Adenocarcinoma: A Case Report

Fusion‐positive non‐small cell lung carcinoma: Biological principles, clinical practice, and diagnostic implications

What Is New in Biomarker Testing at Diagnosis of Advanced Non-Squamous Non-Small Cell Lung Carcinoma? Implications for Cytology and Liquid Biopsy

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