EGFR exon 20 insertion in lung adenocarcinomas among Hispanics (geno1.2-CLICaP)

Zorrilla, Andrés Felipe Cardona; Rojas, Leonardo; Zatarain-Barrón, Zyanya Lucía; Freitas, Helano C.; Granados, Sara T.; Castillo, O.; Oblitas, George; Corrales, Luis; Castro, Christian David; Ruíz-Patiño, Alejandro; Martín, Claudio; Pérez, M. A.; Gonzalez, L.A.; Chirinos, Luis; Vargas, Carlos; Carranza, Hernán; Otero, Jorge; Rodríguez, July; Rodriguez, Jenny; Archila, Pilar; Lema, Mauricio; Madiedo, José Acosta; Karachaliu, Niki; Wills, Beatriz; Pino, Luis Eduardo; Lima, Vladimir de; Rosell, Rafael; Arrieta, Óscar; CLICaP,

doi:10.1016/j.lungcan.2018.10.007

Cited by 54 publications

(60 citation statements)

References 36 publications

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“…Tumors with ≥1% of tumor cells stained in membrane were considered positive for PD‐L1 7 . PD‐L1 immunohistochemistry (Clone 22C3) was graded by a tumor positive score (TPS) system.…”

Section: Methodsmentioning

confidence: 99%

“…Most patients with NSCLC harboring sensitizing epidermal growth factor receptor (EGFR) mutations confer a high response rate of 70%–80% to EGFR‐tyrosine kinase inhibitors (TKIs) such as erlotinib, gefitinib, and afatinib 3–5 . However, approximately 4%–12% of EGFR ‐mutant NSCLC tumors have in‐frame insertions within exon 20, named EGFR Ex20ins, and are generally insensitive to first‐ or second‐generation EGFR‐TKIs due to the modified structures of their kinase domains (except for A763_764insFQEA), 6–8 resulting in a dismal prognosis 9,10 …”

Section: Introductionmentioning

confidence: 99%

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Immune microenvironment features and efficacy of PD‐1/PD‐L1 blockade in non‐small cell lung cancer patients with EGFR or HER2 exon 20 insertions

et al. 2020

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Background: Insertions in exon 20 (Ex20ins) of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are relatively insensitive to firstand second-generation EGFR-tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). This study aimed to investigate the immune microenvironment features and efficacy of PD-1/PD-L1 blockade of NSCLC with EGFR and HER2 Ex20ins. Methods: Clinical characteristics, coexisting mutations, and outcomes to EGFR-TKIs and immune checkpoint blockade were reviewed for NSCLC patients with exon 20 mutations of EGFR or HER2. Data obtained included the molecular spectrum (extended genotyping for mutations in 324 cancer-related genes), as well as tumor mutational burden (TMB), PD-L1 protein expression, and the abundance of CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs). Results: A total of 1270 NSCLC patients were identified. Of these, 504 (39.7%) cases had EGFR mutations and 6.9% (35/504) of them had EGFR Ex20ins. Meanwhile, 21 (1.7%) cases with HER2 Ex20ins were detected. Comprehensive genomic profiling identified A767_V769dup variant (25.0%) was the most common type in tumors with EGFR Ex20ins. Co-occurring mutations were not uncommon including TP53 (45%), PIK3CA (20%), CDKN2A (10%), and EGFR amplification (20%). The average TMB was 3.3 mutations/megabase. PD-L1 expression in patients with EGFR Ex20ins was significantly higher than for those with HER2 mutations (48.6% vs. 19.0%, P = 0.027). High TMB and PD-L1 expression was independently associated with significantly poor prognosis (P = 0.025, P = 0.045, respectively) while there was no association between CD4+/CD8+ TILs and prognosis in EGFR or HER2 mutant NSCLC. Finally, patients harboring EGFR Ex20ins seemed to be sensitive to PD-1/PD-L1 blockage whereas it showed limited efficacy in patients with HER2 Ex20ins. Conclusions: NSCLC patients with EGFR/HER2 Ex20ins had similar genomic characteristics and distinct immune features. Patients with EGFR Ex20ins had significantly higher PD-L1 expression than those with HER2 mutations, which may be the potential reason for the different responses to PD-1/PD-L1 blockage.

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“…Tumors with ≥1% of tumor cells stained in membrane were considered positive for PD‐L1 7 . PD‐L1 immunohistochemistry (Clone 22C3) was graded by a tumor positive score (TPS) system.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immune microenvironment features and efficacy of PD‐1/PD‐L1 blockade in non‐small cell lung cancer patients with EGFR or HER2 exon 20 insertions

et al. 2020

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“…79 However, in the phase II KCSG-LU15-09 study trial, 80 which enrolled 35 patients with uncommon EGFR mutations (exon 20 insertions excluded), osimertinib gave an RR of 50% and a median PFS of 8.2 months. EGFR exon20 insertions represent approximately 2% of all NSCLC 81,82 ; they comprise the third most common EGFR mutation subtype, 81 and the RR to EGFR TKIs is very poor. They represent a heterogeneous group of EGFR mutations, and chemotherapy is, for instance, the SoC first-line treatment.…”

Section: Targeted Therapies In Advanced Nsclcmentioning

confidence: 99%

Advanced-Stage Non–Small Cell Lung Cancer: Advances in Thoracic Oncology 2018

Remón

Ahn

Girard

et al. 2019

Journal of Thoracic Oncology

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In 2018 research in the field of advanced NSCLCs led to an expanded reach and impact of immune checkpoint inhibitors (ICIs) as part of a frontline treatment strategy, regardless of histologic subtype, with ICI use extended to include stage III disease, shifting the prognosis of all these patients. This new standard first-line approach opens a gap in standard second-line treatment, and older combinations may again become standard of care after progression during treatment with an ICI. The characterization of predictive *Corresponding author. Disclosure: Dr. Remon reports honoraria from Merck Sharp and Dohme and Boehringer Ingelheim for serving as an adviser, speaker fees from Pfizer, personal fees and nonfinancial support from Ose Immunotherapeutics, personal fees from Bristol-Myers Squibb and AstraZeneca for travel and serving as an adviser, and reimbursement fees for travel expenses from Roche outside the submitted work. Dr. Ahn reports personal fees from AstraZeneca, Takeda,

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“…PD-L1 expression was significantly higher in patients with wild-type EGFR than those with EGFR mutations [ 11 ]. Cardona et al reported that 81.7% of patients with EGFR exon 20 insertions had TPS of PD-L1 of ≥1% expression [ 12 ]. PD-L1 expression may be associated with different types of EGFR mutation status.…”

Section: Discussionmentioning

confidence: 99%

Good response with durvalumab after chemoradiotherapy for epidermal growth factor receptor exon 20 insertion adenocarcinoma: A case report

Matsuura

Morikawa

Ito

et al. 2020

Respiratory Medicine Case Reports

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Epidermal growth factor receptor (EGFR) exon 20 insertion is not associated with sensitivity to EGFR tyrosine kinase inhibitors and chemotherapy. Here, we report the case of a 41-year-old man who presented a right lower lobe nodule and mediastinal lymph node enlargement diagnosed as EGFR exon 20 insertion adenocarcinoma with high-expression programmed cell death ligand 1 (PD-L1). He showed stable disease to chemoradiation treatment at the primary tumor site. However, durvalumab treatment has good response. Non-small cell lung cancer with EGFR exon 20 insertion and high PD-L1 expression may be treated with immunotherapy exposure.

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EGFR exon 20 insertion in lung adenocarcinomas among Hispanics (geno1.2-CLICaP)

Cited by 54 publications

References 36 publications

Immune microenvironment features and efficacy of PD‐1/PD‐L1 blockade in non‐small cell lung cancer patients with EGFR or HER2 exon 20 insertions

Immune microenvironment features and efficacy of PD‐1/PD‐L1 blockade in non‐small cell lung cancer patients with EGFR or HER2 exon 20 insertions

Advanced-Stage Non–Small Cell Lung Cancer: Advances in Thoracic Oncology 2018

Good response with durvalumab after chemoradiotherapy for epidermal growth factor receptor exon 20 insertion adenocarcinoma: A case report

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