Letter to the Editor
Long duration of immunotherapy in a STK11 mutated/KRAS wild-type non-small cell lung cancer patient
I. Dominguesa,1,
, S. Cedresb, A. Callejob, A. Vivancosc, A. Martinez-Martib, E. Felipb
Corresponding author
a Medical Oncology Department, Portuguese Institute of Oncology of Coimbra, Coimbra, Portugal
b Medical Oncology Department, Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
c Cancer Genomics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
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KRAS (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>48); EGFR (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>47); ERBB2 (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>11); MET (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>9); BRAF (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>9); ALK (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>9); PI3KCA (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>8); ROS (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3); RET (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2); PTEN (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2); ERBB4 (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "D. 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"apellidos" => "Domingues" "email" => array:1 [ 0 => "isabelcpdomingues@gmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "fn0005" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "S." "apellidos" => "Cedres" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "A." "apellidos" => "Callejo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "A." "apellidos" => "Vivancos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 4 => array:3 [ "nombre" => "A." "apellidos" => "Martinez-Marti" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 5 => array:3 [ "nombre" => "E." "apellidos" => "Felip" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Medical Oncology Department, Portuguese Institute of Oncology of Coimbra, Coimbra, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Medical Oncology Department, Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Cancer Genomics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1672 "Ancho" => 2322 "Tamanyo" => 237197 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Sequence of treatments and outcomes. DP: disease progression. PR: partial response. STK11: serine/threonine kinase 11 gene. VHIO: Vall d’Hebron Intitute of Oncology. WES: whole exome sequencing.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Serine/threonine kinase 11 gene (<span class="elsevierStyleItalic">STK11</span>) codes a kinase involved in the regulation of cell growth, polarity and motility, through phosphorylation of adenosine monophosphate-activated protein kinase (AMPK). Somatic mutations have been reported in up to 30% of Caucasian non-squamous non-small cell lung cancer (NSCLC) patients. <span class="elsevierStyleItalic">STK11</span> mutations may assume oncogenic functions, associated to reduced survival in lung adenocarcinoma.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> We present a case of a <span class="elsevierStyleItalic">STK11</span> mutated lung adenocarcinoma presenting a good outcome with immunotherapy.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 51-year-old female patient, light smoker, diagnosed in May/2015 with two synchronic tumours: lung adenocarcinoma cT2aN2M1c (one cerebellar asymptomatic lesion; <span class="elsevierStyleItalic">EGFR</span> wild-type, <span class="elsevierStyleItalic">ALK/ROS1-, KRAS</span>-, <span class="elsevierStyleItalic">HER2</span>-, PD-L1<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>1% by 22C3 assay); and breast invasive ductal carcinoma grade 3, cT2N0M0, hormonal receptors positive (ER 100%, PR 45%), HER2- and Ki-6740%. Whole exome sequencing of lung tumour showed a somatic S69* variant in <span class="elsevierStyleItalic">STK11</span> gene (<span class="elsevierStyleItalic">STK11</span> c.208C>A) at 27% allelic frequency, without additional targetable mutations, and a tumour mutational burden (TMB) of 4.9 mutations/megabase (<10 mutations/megabase).</p><p id="par0015" class="elsevierStylePara elsevierViewall">She started chemoradiotherapy for lung cancer and stereotactic radiosurgery of cerebellar metastasis, as an oligometastatic NSCLC. After 2 months, disease progression (DP) was observed with new adrenal lesions.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Second line docetaxel was started, presenting DP of NSCLC after one month, but with breast cancer reduction.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In September/2015, the patient started a third line with nivolumab. Partial response was observed at two months and patient continued with the immunotherapy. After fifteen months lung and breast tumours increased, and local therapy was performed (stereotactic radiotherapy for lung, followed by breast lumpectomy, pT1cN0M0). Post-lumpectomy RT was considered to have no further benefit. She started adjuvant therapy with letrozole.</p><p id="par0030" class="elsevierStylePara elsevierViewall">In March/2018, after thirty months, lung tumour had a second DP under immunotherapy, and underwent a new biopsy. At this point, this lung biopsy along the primary breast tumour were analysed through the VHIO-300 panel (450 genes) revealing presence of the <span class="elsevierStyleItalic">STK11</span> mutation in lung at DP (52.4% mutant fraction) and complete absence of the variant in breast.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Despite DP, she remained asymptomatic, with good tolerance to nivolumab and letrozole. Immunotherapy proceeded until present (thirty-nine months), given the clinical benefit (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">In synchronous tumours, the most advanced assumes a prognostic importance. Although lung and breast tumours are common in females, their synchronous diagnosis is infrequent.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> The patient's tumours didn’t present a common mutational background.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Molecular classification of NSCLC has a direct impact on prognosis and treatment choices. <span class="elsevierStyleItalic">STK11</span> is thought to have a role on pulmonary tumorigenesis, often associated with <span class="elsevierStyleItalic">KRAS</span>.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">3,4</span></a> The reported <span class="elsevierStyleItalic">STK11</span> pS69* mutation results in a premature stop codon within its kinase domain, associated to more aggressive tumours, shorter progression-free survival and overall survival.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,3</span></a> Additionally, this mutation has been associated with significantly shorter time on PD-1/PD-L1 blockade therapy in NSCLC (or even resistance),<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> possibly by reducing density of tumour infiltrating cytotoxic CD8+T lymphocytes.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> Despite the <span class="elsevierStyleItalic">STK11</span> mutation, our patient presented a long survival and a clinical benefit from immunotherapy, as well as from thoracic radiotherapy and its possible abscopal effect.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0050" class="elsevierStylePara elsevierViewall">This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of interest</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflicts of interest" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "1" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Permanent address.</p>" "identificador" => "fn0005" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1672 "Ancho" => 2322 "Tamanyo" => 237197 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Sequence of treatments and outcomes. DP: disease progression. PR: partial response. STK11: serine/threonine kinase 11 gene. VHIO: Vall d’Hebron Intitute of Oncology. WES: whole exome sequencing.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Different prognostic impact of STK11 mutations in non-squamous non-small-cell lung cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Pécuchet" 1 => "P. Laurent-Puig" 2 => "A. Mansuet-Lupo" 3 => "A. Legras" 4 => "M. Alifano" 5 => "K. Pallier" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Oncotarget" "fecha" => "2017" "volumen" => "8" "paginaInicial" => "23831" "paginaFinal" => "23840" "itemHostRev" => array:3 [ "pii" => "S0211139X1630004X" "estado" => "S300" "issn" => "0211139X" ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multiple primary tumours: challenges and approaches, a review" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Vogt" 1 => "S. Schmid" 2 => "K. Heinimann" 3 => "H. Frick" 4 => "C. Herrmann" 5 => "T. Cerny" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/esmoopen-2017-000172" "Revista" => array:5 [ "tituloSerie" => "ESMO Open" "fecha" => "2017" "volumen" => "2" "paginaInicial" => "e000172" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28761745" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "STK11/LKB1 mutations and PD-1 inhibitor resistance in KRAS-mutant lung adenocarcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Skoulidis" 1 => "M.E. Goldberg" 2 => "D.M. Greenawalt" 3 => "M.D. Hellmann" 4 => "M.M. Awad" 5 => "J.F. Gainor" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Cancer Discov" "fecha" => "2018" "volumen" => "8" "paginaInicial" => "822" "paginaFinal" => "835" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "LKB1 modulates lung cancer differentiation and metastasis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Ji" 1 => "M.R. Ramsey" 2 => "D.N. Hayes" 3 => "C. Fan" 4 => "K. McNamara" 5 => "P. Kozlowski" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nature06030" "Revista" => array:6 [ "tituloSerie" => "Nature" "fecha" => "2007" "volumen" => "448" "paginaInicial" => "807" "paginaFinal" => "810" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17676035" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "STK11/LKB1 deficiency promotes neutrophil recruitment and proinflammatory cytokine production to suppress T-cell activity in the lung tumor microenvironment" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Koyama" 1 => "E.A. Akbay" 2 => "Y.Y. Li" 3 => "A.R. Aref" 4 => "F. Skoulidis" 5 => "G.S. Herter-Sprie" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/0008-5472.CAN-15-1439" "Revista" => array:6 [ "tituloSerie" => "Cancer Res" "fecha" => "2016" "volumen" => "76" "paginaInicial" => "999" "paginaFinal" => "1008" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26833127" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/25310437/0000002600000001/v1_202002062105/S2531043719300947/v1_202002062105/en/main.assets" "Apartado" => array:4 [ "identificador" => "82163" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/25310437/0000002600000001/v1_202002062105/S2531043719300947/v1_202002062105/en/main.pdf?idApp=UINPBA00004E&text.app=https://journalpulmonology.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2531043719300947?idApp=UINPBA00004E" ]
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| 2021 February | 144 | 36 | 180 |
| 2021 January | 157 | 35 | 192 |
| 2020 December | 116 | 34 | 150 |
| 2020 November | 150 | 32 | 182 |
| 2020 October | 127 | 35 | 162 |
| 2020 September | 145 | 45 | 190 |
| 2020 August | 182 | 48 | 230 |
| 2020 July | 166 | 39 | 205 |
| 2020 June | 195 | 38 | 233 |
| 2020 May | 180 | 40 | 220 |
| 2020 April | 221 | 31 | 252 |
| 2020 March | 176 | 55 | 231 |
| 2020 February | 181 | 66 | 247 |
| 2020 January | 120 | 25 | 145 |
| 2019 December | 97 | 15 | 112 |
| 2019 November | 90 | 26 | 116 |
| 2019 October | 66 | 23 | 89 |
| 2019 September | 53 | 21 | 74 |
| 2019 August | 22 | 31 | 53 |
Show all
