Scientific Letter
Acquired T790M-positive Squamous Cell Lung Carcinoma that Responded to Osimertinib
Carcinoma pulmonar de células escamosas con mutación T790M adquirida que respondió a osimertinib
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(B) Haematoxylin and eosin staining of the biopsy specimen. Histopathological findings of the biopsy specimen showed squamous cell carcinoma (magnification 200×). (C) CT scan showed regrowth of the tumour (arrow). (D) The tumour showed shrinkage after osimertinib administration (arrow).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Masahiro Yamasaki, Kunihiko Funaishi, Wakako Daido, Noboru Hattori" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Masahiro" "apellidos" => "Yamasaki" ] 1 => array:2 [ "nombre" => "Kunihiko" "apellidos" => "Funaishi" ] 2 => array:2 [ "nombre" => "Wakako" "apellidos" => "Daido" ] 3 => array:2 [ "nombre" => "Noboru" "apellidos" => "Hattori" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S1579212919303015" "doi" => "10.1016/j.arbr.2019.04.013" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212919303015?idApp=UINPBA00003Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289619302200?idApp=UINPBA00003Z" "url" => "/03002896/0000005500000011/v4_202003140718/S0300289619302200/v4_202003140718/en/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S1579212919303027" "issn" => "15792129" "doi" => "10.1016/j.arbr.2019.03.016" "estado" => "S300" "fechaPublicacion" => "2019-11-01" "aid" => "2139" "copyright" => "SEPAR" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Arch Bronconeumol. 2019;55:604-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 5 "formatos" => array:2 [ "HTML" => 3 "PDF" => 2 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Telematic Multi-physician Decision-making for Improving CPAP Prescription in Sleep Apnoea" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "604" "paginaFinal" => "606" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Toma de decisiones compartida por vía telemática para mejorar la prescripción de la CPAP en la apnea del sueño" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2995 "Ancho" => 1194 "Tamanyo" => 233102 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Probability of correct CPAP prescription when the decision is taken by 1 physician (brown columns) or by a 3-physician group (green columns), for the different 7 possible (‘yes’–‘no’) recommendations from 6 physicians (0–6, 1–5, 2–4, 3–3, 4–2, 5–1 and 6–0). In case of unanimous (0–6 or 6–0) or draw (3–3) recommendations there is no statistical advantage when the decision is taken from 3 or 1 physicians. In the other cases, 3-physician decision is advantageous as compared with 1-physician decision. (B) Left: Distribution of 6-physician recommendations for the 40 patients with mild–moderate OSA (AHI<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>40<span class="elsevierStyleHsp" style=""></span>events/h). Gray: recommendations resulting in no statistical advantage when the decision is made by 3 or 1 physicians; Black: recommendations for which decision-making by 3 instead of 1 physician increases correct decision probability. Right: Expected error in CPAP prescription when the decision is taken by 3 physicians (green column) instead 1 physician (brown column). (C) Same as in (B) but only for moderate OSA patients (15<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>AHI<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>40 events/h).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ramon Farré, Daniel Navajas, David Gozal, Josep M. Montserrat" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Ramon" "apellidos" => "Farré" ] 1 => array:2 [ "nombre" => "Daniel" "apellidos" => "Navajas" ] 2 => array:2 [ "nombre" => "David" "apellidos" => "Gozal" ] 3 => array:2 [ "nombre" => "Josep M." 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(B) Immunohistochemical study positive for cytokeratin AE1/AE3. (C) Marked positivity of all atypical epithelial cells for EBER (EBV-encoded small nuclear RNA).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Marta Llabrés de Prada, Roberto Martin-Deleon, Daniel Martinez, Carmen M. Lucena, Carles Agustí" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Marta" "apellidos" => "Llabrés de Prada" ] 1 => array:2 [ "nombre" => "Roberto" "apellidos" => "Martin-Deleon" ] 2 => array:2 [ "nombre" => "Daniel" "apellidos" => "Martinez" ] 3 => array:2 [ "nombre" => "Carmen M." 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(B) Haematoxylin and eosin staining of the biopsy specimen. Histopathological findings of the biopsy specimen showed squamous cell carcinoma (magnification 200×). (C) CT scan showed regrowth of the tumour (arrow). (D) The tumour showed shrinkage after osimertinib administration (arrow).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Osimertinib is an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) that has demonstrated efficacy against T790M-positive non-small cell lung cancer (NSCLC).<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> NSCLCs with the T790M mutation are mostly adenocarcinomas, and whether osimertinib is effective against T790M-positive squamous cell carcinoma (SqCC) remains uncertain. Here, we report a case of acquired T790M-positive SqCC that responded to osimertinib therapy.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 68-year-old woman arrived at our hospital with a chief complaint of prolonged productive cough. She was a never-smoker and had Parkinson's disease. She had been treated with deep brain stimulation and medication. However, her physical activity was relatively low. A chest radiography showed a mass in the right hilar region of the lower lungs, and a computed tomography (CT) scan showed a mass lesion in the right hilar region of the lower lobe of the right lung (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). The serum concentration of cytokeratin 19 fragment (CYFRA 21-1) was elevated (12.5<span class="elsevierStyleHsp" style=""></span>ng/mL), and other tumour markers were within the normal ranges. Subsequently, she underwent bronchoscopy, and the biopsy specimen was pathologically examined. As a result, the tumour was diagnosed as SqCC (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). The specimen showed p63 positivity on immunohistochemical staining and EGFR mutation positivity (exon 19 deletion and exon 20 insertion). She underwent [18F]-fluorodeoxyglucose (FDG) positron emission tomography; results showed high FDG uptake in the right hilar lymph node and spleen; finally, her condition was diagnosed as primary lung SqCC, cT4N1M1b, stage IVA.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">She was administered 150<span class="elsevierStyleHsp" style=""></span>mg erlotinib daily. Four weeks later, the tumour lesions showed shrinkage, and the serum CYFRA 21-1 level was normalised. However, only three months later, the tumour showed regrowth, and the serum CYFRA 21-1 was elevated again (4.8<span class="elsevierStyleHsp" style=""></span>ng/mL). As second-line treatment, chemotherapy using carboplatin and <span class="elsevierStyleItalic">nab</span>-paclitaxel was initiated. After the administration of two cycles of this regimen, the tumour shrunk, and the serum CYFRA 21-1 levels normalised. However, after four cycles, the tumour showed regrowth (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C), and the serum CYFRA 21-1 levels elevated again (4.2<span class="elsevierStyleHsp" style=""></span>ng/mL). The serum carcinoembryonic antigen and sialyl Lewis X-1 levels were not increased. A liquid biopsy was performed to detect EGFR mutations, and T790M and exon 19 deletion were detected.</p><p id="par0020" class="elsevierStylePara elsevierViewall">As third-line treatment, 80<span class="elsevierStyleHsp" style=""></span>mg osimertinib was administered daily. No particular adverse event was observed. After three weeks, the tumour showed shrinkage on CT scan (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>D), and the serum CYFRA 21-1 level normalised. After three months of osimertinib therapy, the tumour showed further shrinkage on CT scan. The patient is alive with no complaints or disease progression, and has continued osimertinib treatment for a total of 5 months.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In this case, we found that osimertinib was effective for a patient with acquired T790M-positive SqCC. To the best of our knowledge, only one case of a patient with acquired T790M-positive SqCC who showed response to osimertinib has been reported previously,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> along with other SqCC transformation cases.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">3,4</span></a> Osimertinib might be effective for T790M-positive SqCC; recently, osimertinib has been used as first-line therapy for EGFR mutation-positive NSCLC.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a> It remains uncertain whether osimertinib is effective against T790M-negative EGFR mutation-positive SqCC. Further studies are required to evaluate the efficacy of osimertinib for T790M-negative EGFR mutation-positive SqCC.</p><p id="par0030" class="elsevierStylePara elsevierViewall">EGFR mutations in SqCC should be examined, at least in never-smoker cases. SqCC with EGFR mutations are found at low frequencies, and EGFR-TKIs are poorly effective against SqCC with EGFR mutations.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">6</span></a> However, SqCC with EGFR mutations have been found more frequently in never-smoker cases<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">7</span></a>; in addition, considering the present case and the previous report,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> osimertinib might show efficacy against EGFR-positive SqCC after the acquisition of T790M resistance mutation. To use EGFR-TKIs as a treatment alternative for EGFR-positive SqCC, EGFR mutations in SqCC should be examined.</p><p id="par0035" class="elsevierStylePara elsevierViewall">T790M-positivity of the present case was diagnosed by liquid biopsy examination, and a histopathological examination of the re-biopsy specimen was not performed. Therefore, the transformation from SqCC to other histopathological subtypes cannot be denied. However, the tumour markers in the present case showed that the tumour was consistently CYFRA 21-1, and the other tumour markers were not elevated. These findings revealed that in the present case, the histopathological subtype probably did not transform to other subtypes during treatment.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Afatinib therapy has been described as a better treatment alternative for EGFR mutation-positive SqCC compared to erlotinib therapy. In LUX-Lung 8, a randomised phase III study, afatinib showed better progression free survival than erlotinib did in SqCC cases.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">8</span></a> Moreover, in a sub-analysis, afatinib showed further better progression-free survival than erlotinib did in ERBB (EGFR, HER2, HER3, and HER4) mutation-positive SqCC cases.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">9</span></a> In the present case, erlotinib was used as a first-line therapy because of the patient's low physical activity. However, afatinib should be used for EGFR mutation-positive SqCC, if possible. Further, in the future, it is important to evaluate which among the two EGFR-TKIs, afatinib or osimertinib, is more potent as the first-line treatment for EGFR mutation-positive SqCC.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 899 "Ancho" => 1255 "Tamanyo" => 194073 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Computed tomography (CT) scan showed a mass lesion in the right hilar region of the lower lobe of the right lung. (B) Haematoxylin and eosin staining of the biopsy specimen. Histopathological findings of the biopsy specimen showed squamous cell carcinoma (magnification 200×). (C) CT scan showed regrowth of the tumour (arrow). (D) The tumour showed shrinkage after osimertinib administration (arrow).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0050" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Osimertinib in pretreated T790M-positive advanced non-small-cell lung cancer: AURA study phase II extension component" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.C. Yang" 1 => "M.J. Ahn" 2 => "D.W. Kim" 3 => "S.S. Ramalingam" 4 => "L.V. Sequist" 5 => "W.C. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 1 | 1 | 2 |
| 2024 October | 33 | 15 | 48 |
| 2024 September | 30 | 13 | 43 |
| 2024 August | 40 | 33 | 73 |
| 2024 July | 25 | 15 | 40 |
| 2024 June | 38 | 24 | 62 |
| 2024 May | 51 | 19 | 70 |
| 2024 April | 20 | 30 | 50 |
| 2024 March | 26 | 18 | 44 |
| 2024 February | 25 | 18 | 43 |
| 2023 March | 9 | 3 | 12 |
| 2023 February | 36 | 19 | 55 |
| 2023 January | 34 | 40 | 74 |
| 2022 December | 49 | 34 | 83 |
| 2022 November | 45 | 23 | 68 |
| 2022 October | 63 | 34 | 97 |
| 2022 September | 27 | 20 | 47 |
| 2022 August | 42 | 33 | 75 |
| 2022 July | 39 | 44 | 83 |
| 2022 June | 20 | 19 | 39 |
| 2022 May | 36 | 34 | 70 |
| 2022 April | 32 | 22 | 54 |
| 2022 March | 34 | 32 | 66 |
| 2022 February | 19 | 26 | 45 |
| 2022 January | 16 | 18 | 34 |
| 2021 December | 27 | 34 | 61 |
| 2021 November | 29 | 34 | 63 |
| 2020 April | 1 | 0 | 1 |
| 2020 March | 3 | 0 | 3 |
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