EGFR-RAD51 fusion in lung adenocarcinoma with systemic and intracranial response to osimertinib: A case report and review of the literature

Sperandio, Rubens Copia; Tostes, Francinne T.; Campregher, Paulo Vidal; Paes, V.; Moura, Fernando; Schvartsman, Gustavo

doi:10.1016/j.lungcan.2022.02.006

Cited by 8 publications

(5 citation statements)

References 12 publications

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“…Notably, deep response and prolonged benefit were also observed with osimertinib in patients with both EGFR fusion and EGFR-KDD, in line with previous reports. 9 , 27 , 28 Data on sensitivity to TKIs are missing for Y801C, 29 which was associated with no response in our study. E868Q, V738_A743del, A702_K728del, and L747Q have never been described in cancers and R831C has never been found in lung cancers.…”

Section: Discussionmentioning

confidence: 78%

“…In the remaining 10%-20% of EGFR -mutated NSCLC cases, uncommon alterations of EGFR (uEGFR) comprise G719X in exon 18, L861Q in exon 21, and S768I in exon 20, which are the most frequent (major uEGFR), and a variety of rarer alterations (minor uEGFR) such as gene fusions, duplications of the EGFR-kinase domain (EGFR-KDD), and mutations in exons 2-15. 7 , 8 , 9 Such mutations may occur as single alterations or together with other common or uncommon EGFR mutations (compound or complex mutations). 10 …”

Section: Introductionmentioning

confidence: 99%

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Activity of osimeRTInib in non-small-cell lung Cancer with UNcommon epidermal growth factor receptor mutations: retrospective Observational multicenter study (ARTICUNO)

Pizzutilo,

Agostara,

Oresti

et al. 2024

ESMO Open

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Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Activity of osimeRTInib in non-small-cell lung Cancer with UNcommon epidermal growth factor receptor mutations: retrospective Observational multicenter study (ARTICUNO)

Pizzutilo,

Agostara,

Oresti

et al. 2024

ESMO Open

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“…In recent years, EGFR fusions in particular have been in the spotlight with several case reports/series being reported in lung AC. Although there is currently no approved drug specifically for EGFR fusions, many of these cases have been treated with EGFR TKIs and antitumor responses have been documented, both in vitro and in clinics [ 30 , 31 , 32 , 33 ]. Due to prevailing testing strategies that are often restricted to lung AC, data about fusion events in lung SCC are exceedingly rare [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Expanding Broad Molecular Reflex Testing in Non-Small Cell Lung Cancer to Squamous Histology

Zacharias,

Konjic,

Kratochwill

et al. 2024

Cancers

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Due to the success story of biomarker-driven targeted therapy, most NSCLC guidelines agree that molecular reflex testing should be performed in all cases with non-squamous cell carcinoma (non-SCC). In contrast, testing recommendations for squamous cell carcinoma (SCC) vary considerably, specifically concerning the exclusion of patients of certain age or smoking status from molecular testing strategies. We performed a retrospective single-center study examining the value of molecular reflex testing in an unselected cohort of 316 consecutive lung SCC cases, tested by DNA- and RNA-based next-generation sequencing (NGS) at our academic institution between 2019 and 2023. Clinicopathological data from these cases were obtained from electronic medical records and correlated with sequencing results. In 21/316 (6.6%) cases, we detected an already established molecular target for an approved drug. Among these were seven cases with an EGFR mutation, seven with a KRAS G12C mutation, four with an ALK fusion, two with an EGFR fusion and one with a METex14 skipping event. All patients harboring a targetable alteration were >50 years of age and most of them had >15 pack-years, questioning restrictive molecular testing strategies. Based on our real-world data, we propose a reflex testing workflow using DNA- and RNA-based NGS that includes all newly diagnosed NSCLC cases, irrespective of histology, but also irrespective of age or smoking status.

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“…Although EGFR gene fusions are rare, clinical responses in EGFR fusion-driven tumors have been reported with EGFR TKIs ( 40 , 41 ). The EGFR :: CCDC6 fusion is novel, to our knowledge; however CCDC6 -tyrosine kinase fusions (for example with ALK , ROS1 , or RET ), are recognized–and druggable–driver events in lung cancer ( 42 ).…”

Section: Discussionmentioning

confidence: 99%

Activity of afatinib in patients with NSCLC harboring novel uncommon EGFR mutations with or without co-mutations: a case report

Christopoulos,

Herster,

Hoffknecht

et al. 2024

Front. Oncol.

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Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) represent first-line standard of care in unresectable EGFR mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC). However, 10–20% of patients with EGFRm+ NSCLC have uncommon EGFR variants, defined as mutations other than L858R substitutions or exon 19 deletions. NSCLC harboring uncommon EGFR mutations may demonstrate lower sensitivity to targeted agents than NSCLC with L858R or exon 19 deletion mutations. Prospective clinical trial data in patients with NSCLC uncommon EGFR mutations are lacking. Afatinib is a second-generation TKI and the only Food and Drug Administration-approved drug for some of the more prevalent uncommon EGFR mutations. We present a series of seven case reports describing clinical outcomes in afatinib-treated patients with NSCLC harboring a diverse range of extremely rare mutations with or without co-mutations affecting other genes. EGFR alterations included compound mutations, P-loop αC-helix compressing mutations, and novel substitution mutations. We also present a case with NSCLC harboring a novel EGFR::CCDC6 gene fusion. Overall, the patients responded well to afatinib, including radiologic partial responses in six patients during treatment. Responses were durable for three patients. The cases presented are in line with a growing body of clinical and preclinical evidence that indicating that NSCLC with various uncommon EGFR mutations, with or without co-mutations, may be sensitive to afatinib.

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EGFR-RAD51 fusion in lung adenocarcinoma with systemic and intracranial response to osimertinib: A case report and review of the literature

Cited by 8 publications

References 12 publications

Activity of osimeRTInib in non-small-cell lung Cancer with UNcommon epidermal growth factor receptor mutations: retrospective Observational multicenter study (ARTICUNO)

Activity of osimeRTInib in non-small-cell lung Cancer with UNcommon epidermal growth factor receptor mutations: retrospective Observational multicenter study (ARTICUNO)

Expanding Broad Molecular Reflex Testing in Non-Small Cell Lung Cancer to Squamous Histology

Activity of afatinib in patients with NSCLC harboring novel uncommon EGFR mutations with or without co-mutations: a case report

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