Outcome of EGFR-mutated adenocarcinoma NSCLC patients with changed phenotype to squamous cell carcinoma after tyrosine kinase inhibitors: A pooled analysis with an additional case

Roca, Elisa; Pozzari, Marta; Vermi, William; Tovazzi, Valeria; Baggi, Alice; Amoroso, Vito; Nonnis, Daniela; Intagliata, Salvatore; Berruti, Alfredo

doi:10.1016/j.lungcan.2018.11.016

Cited by 38 publications

(48 citation statements)

References 32 publications

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“…Thus, the prognosis of lung cancer patients with squamous cell transformation and EGFR T790M mutation appears to be worse than that of patients with only EGFR T790M mutation. This is consistent with a report by Roca et al .…”

Section: Discussionsupporting

confidence: 94%

“…Squamous cell transformation as a resistance mechanism to EGFR inhibitors has been investigated clinically. Roca et al performed a pooled analysis of 17 patients and showed that most of these patients were smokers and harboured original EGFR mutations. In addition to squamous cell transformation, they observed coexisting EGFR T790M mutation in approximately half of the patients.…”

Section: Discussionmentioning

confidence: 99%

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Squamous cell transformation as a mechanism of acquired resistance to tyrosine kinase inhibitor in EGFR‐mutated lung adenocarcinoma: a report of two cases

Uruga

Fujii²,

Nakamura

et al. 2020

Respirology Case Reports

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Pathological transformation to squamous cell carcinoma after epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor treatment has been reported, but details of the transformation remain unclear. We report two cases with transformation to squamous cell carcinoma. The first case was a 61-year-old man who was an ex-smoker with stage IV lung adenocarcinoma harbouring EGFR exon 19 insertion. He experienced squamous cell transformation after 28 months of erlotinib therapy. Next-generation sequencing (NGS) analysis showed EGFR T790M and genomic alterations in PTEN, PDGFR, and HRAS. The second case was a 72-year-old man who was an ex-smoker with stage IV lung adenocarcinoma harbouring EGFR exon 21 L858R. He experienced squamous cell transformation after nine months of erlotinib therapy. NGS analysis showed EGFR T790M and genomic alterations in PTEN, SMARCB1, TP53, and KIT. Both patients had PTEN genomic alterations and the PI3K/AKT/mTOR (mammalian target of rapamycin) pathway might play an important role in squamous cell transformation. Case ReportCase 1 A 61-year-old man who was an ex-smoker underwent computed tomography-guided percutaneous lung biopsy. On the basis of the American Joint Committee on Cancer staging

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Squamous cell transformation as a mechanism of acquired resistance to tyrosine kinase inhibitor in EGFR‐mutated lung adenocarcinoma: a report of two cases

Uruga

Fujii²,

Nakamura

et al. 2020

Respirology Case Reports

View full text Add to dashboard Cite

show abstract

“…Indeed, the trans-differentiation from LAC to SqCC has been described both in humans and in mouse models, often when tumor cells are characterized by inactivation of the tumor suppressor gene LKB1/STK11 , which occurs in up to 20% of LACs [3,7,10,238,239]. Moreover, clinical investigations have identified cases revealing a phenotypic LAC-to-SqCC change at progression during treatment with EGFR-TKIs of all three generations [30,240], which is consistent with the association of this phenotypic conversion with TKI-resistance [7,238]. However, as for SCLC-transformation and EMT, it is debated whether the conversion from LAC to SqCC is a clonal selection or an adaptive histological change resulting in phenotype-switch [240].…”

Section: Clinical and Preclinical Studies Shedding Light On Intrinmentioning

confidence: 99%

Intrinsic resistance to EGFR-Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer: Differences and Similarities with Acquired Resistance

Santoni-Rugiu

Melchior

Urbanska

et al. 2019

Cancers

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126

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Activating mutations in the epidermal growth factor receptor gene occur as early cancer-driving clonal events in a subset of patients with non-small cell lung cancer (NSCLC) and result in increased sensitivity to EGFR-tyrosine-kinase-inhibitors (EGFR-TKIs). Despite very frequent and often prolonged clinical response to EGFR-TKIs, virtually all advanced EGFR-mutated (EGFRM+) NSCLCs inevitably acquire resistance mechanisms and progress at some point during treatment. Additionally, 20–30% of patients do not respond or respond for a very short time (<3 months) because of intrinsic resistance. While several mechanisms of acquired EGFR-TKI-resistance have been determined by analyzing tumor specimens obtained at disease progression, the factors causing intrinsic TKI-resistance are less understood. However, recent comprehensive molecular-pathological profiling of advanced EGFRM+ NSCLC at baseline has illustrated the co-existence of multiple genetic, phenotypic, and functional mechanisms that may contribute to tumor progression and cause intrinsic TKI-resistance. Several of these mechanisms have been further corroborated by preclinical experiments. Intrinsic resistance can be caused by mechanisms inherent in EGFR or by EGFR-independent processes, including genetic, phenotypic or functional tumor changes. This comprehensive review describes the identified mechanisms connected with intrinsic EGFR-TKI-resistance and differences and similarities with acquired resistance and among clinically implemented EGFR-TKIs of different generations. Additionally, the review highlights the need for extensive pre-treatment molecular profiling of advanced NSCLC for identifying inherently TKI-resistant cases and designing potential combinatorial targeted strategies to treat them.

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“…Furthermore, adenocarcinoma (ADC) cells may undergo transformation to a different phenotype. Most published cases involve transformation from ADC to small cell lung cancer (SCLC), and few cases convert from ADC to squamous cell carcinoma (SqCC) (2,3). Moreover, histological transformation during long-term treatment with EGFR-TKIs rarely occurs.…”

Section: Introductionmentioning

confidence: 99%

Transformation from adenocarcinoma to squamous cell carcinoma associated with long‑term administration of EGFR‑TKIs

et al. 2020

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Although patients with non-small cell lung cancer exhibiting EGFR mutations generally respond to tyrosine kinase inhibitors (TKIs), the majority of patients acquire resistance ~1 year after treatment. EGFR T790M mutations, MET or HER2 amplifications and phenotypic transformations contribute to the mechanism of EGFR-TKI resistance. The transformation of small cell lung cancer frequently occurs, although few convert to squamous cell carcinoma associated with the administration of EGFR-TKIs. The current study reports a case of EGFR-mutated adenocarcinoma of the lung that transitioned to squamous cell carcinoma in association with long-term EGFR-TKIs administration.

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Outcome of EGFR-mutated adenocarcinoma NSCLC patients with changed phenotype to squamous cell carcinoma after tyrosine kinase inhibitors: A pooled analysis with an additional case

Cited by 38 publications

References 32 publications

Squamous cell transformation as a mechanism of acquired resistance to tyrosine kinase inhibitor in EGFR‐mutated lung adenocarcinoma: a report of two cases

Squamous cell transformation as a mechanism of acquired resistance to tyrosine kinase inhibitor in EGFR‐mutated lung adenocarcinoma: a report of two cases

Intrinsic resistance to EGFR-Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer: Differences and Similarities with Acquired Resistance

Transformation from adenocarcinoma to squamous cell carcinoma associated with long‑term administration of EGFR‑TKIs

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