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52. Multiple Low Dose (MLD) therapy: an effective strategy to treat EGFR inhibitor-resistant NSCLC tumours

Author

Fernandes Neto, João M., primary, Nadal, Ernest, additional, Ooft, Salo N, additional, Bosdriesz, Evert, additional, Farre, Lourdes, additional, McLean, Chelsea, additional, Klarenbeek, Sjoerd, additional, Jurgens, Anouk, additional, Hagen, Hannes, additional, Wang, Liqin, additional, Felip, Enriqueta, additional, Martinez-Marti, Alex, additional, Voest, Emile, additional, Wessels, Lodewyk F.A., additional, van Tellingen, Olaf, additional, Villanueva, Alberto, additional, and Bernards, René, additional

Published
2019
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54. Haematological biomarkers of pathological response on neo-adjuvant chemo-immunotherapy treatment for resectable stage IIIA non-small cell lung cancer (NSCLC) patients.

Author

Laza Briviesca, Raquel, primary, Cruz Bermudez, Alberto, additional, Barquin, Miguel, additional, Nadal, Ernest, additional, Insa, Amelia, additional, Garcia-Campelo, Rosario, additional, De Dios Alvarez, Noemi, additional, Domine, Manuel, additional, Massuti, Bartomeu, additional, Majem, Margarita, additional, Rodriguez-Abreu, Delvys, additional, Martinez Marti, Alex, additional, Cobo, Manuel, additional, Lopez-Vivanco, Guillermo, additional, del Barco, Elvira, additional, Bernabé, Reyes, additional, Vinolas, Nuria, additional, Barneto, Isidoro, additional, Viteri, Santiago, additional, and Provencio-Pulla, Mariano, additional

Published
2019
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55. Analysis of mismatch repair (MMR) proteins expression in a series of malignant pleural mesothelioma (MPM) patients.

Author

Cedres, Susana, primary, Ponce Aix, Santiago, additional, Callejo, Ana, additional, Pardo, Nuria, additional, Navarro, Alejandro, additional, Martinez Marti, Alex, additional, Sansano, Irene, additional, Enguita, Ana Belen, additional, Rodriguez, Gisela, additional, Monton, Victor, additional, Miquel, Josep M, additional, Viaplana, Cristina, additional, Dienstmann, Rodrigo, additional, and Felip, Enriqueta, additional

Published
2019
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56. Whole exome sequencing (WES) of non-small cell lung cancer (NSCLC) for tumor mutational burden (TMB) analysis and long-term benefit to immune checkpoint inhibitors (ICIs).

Author

Felip, Enriqueta, primary, Navarro, Alejandro, additional, Callejo, Ana, additional, Martinez Marti, Alex, additional, Cedres, Susana, additional, Pardo, Nuria, additional, Ros, Javier, additional, Assaf, Juan David, additional, Pedrola, Anna, additional, Viaplana, Cristina, additional, Sansano, Irene, additional, Jimenez, Jose, additional, Nuciforo, Paolo, additional, Sansó, Miriam, additional, Dienstmann, Rodrigo, additional, Amat, Ramon, additional, Mancuso, Francesco M, additional, and Vivancos, Ana, additional

Published
2019
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57. Additional file 2: Tables S1â 9. of Single-cell transcriptome conservation in cryopreserved cells and tissues

Author

Guillaumet-Adkins, Amy, RodrĂ­Guez-Esteban, Gustavo, Mereu, Elisabetta, Mendez-Lago, Maria, Jaitin, Diego, Villanueva, Alberto, Vidal, August, Martinez-Marti, Alex, Felip, Enriqueta, Vivancos, Ana, Keren-Shaul, Hadas, Heath, Simon, Gut, Marta, Amit, Ido, Gut, Ivo, and Heyn, Holger

Abstract

Table S1. Overview table of experiments. Table S2. Differential gene expression between fresh and cryopreserved K562 cells. (MARS-Seq; top 40 genes). Table S3. Differential gene expression between fresh and cryopreserved HEK293 cells. (MARS-Seq; top 40 genes). Table S4. Differential gene expression between fresh and cryopreserved NIH3T3 cells. (MARS-Seq; top 40 genes). Table S5. Differential gene expression between fresh and cryopreserved MDCK cells. (MARS-Seq; top 40 genes). Table 6: Differential gene expression between fresh and cryopreserved HEK293 cells. (SMARTseq2; top 40 genes). Table 7: Differential gene expression between fresh and cryopreserved K562 cells. (SMARTseq2; top 40 genes). Table S8: Differential gene expression between fresh and cryopreserved PBMC. (MARS-Seq; top 40 genes). Table S9: Differential gene expression between a fresh and cryopreserved PDOX. (MARSseq; top 40 genes). (PDF 40 kb)

Published
2017
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58. Additional file 1: Figures S1–16. of Single-cell transcriptome conservation in cryopreserved cells and tissues

Author

Guillaumet-Adkins, Amy, Rodríguez-Esteban, Gustavo, Mereu, Elisabetta, Mendez-Lago, Maria, Jaitin, Diego, Villanueva, Alberto, Vidal, August, Martinez-Marti, Alex, Felip, Enriqueta, Vivancos, Ana, Keren-Shaul, Hadas, Heath, Simon, Gut, Marta, Amit, Ido, Gut, Ivo, and Heyn, Holger

Abstract

Figure S1. Single cell transcriptome sequencing of 670 fresh and 816 cryopreserved cells using the MARS-Seq (a-c) and the Smart-seq2 (d, e) library preparation protocols. Samples included two human (HEK293 and K562), one mouse (NIH3T3) and one canine (MDCK) cell line, peripheral blood mononuclear cells (PBMC), a primary mouse colon sample and orthotopic tumor xenografts (patient-derived orthotopic xenograft, PDOX). Analyses were split by replicate experiments and conditions. Displayed are the total number of reads per cell (a,d), the total number of detected genes per cell (b,e) and the number of detected transcripts (UMI counts) per cell (c). The results are displayed as boxplot indicating median values (black bar) per experiment and condition. Figure S2. (a-d) Cumulative gene counts split by fresh (red) or cryopreserved (blue) cells and analyzed using randomly sampled cells (average of 100 permutations). Displayed are results for K562 (experiment 1, a), HEK293 (experiment 1, b), NIH3T3 (c) and MDCK (d) cell lines. Figure S3. Distribution of sequencing reads numbers per single cell split by conditions (fresh (red); cryopreserved -80ºC: blue; cryopreserved liquid nitrogen: green). Displayed are the distributions for all MARS-Seq experiments (a-h) indicating the median number of reads per single cell (horizontal lines). Experiment types are indicated. Figure S4. MARS-Seq library complexity assessment of fresh (red) or cryopreserved (blue) cells using the number of uniquely detected transcripts. (a-d) Comparative analysis of the number of sequencing reads and detected transcripts using a linear model. The slope of the regression line was calculated separately for fresh and cryopreserved cells. Displayed are results for K562 (experiment 1, a), HEK293 (experiment 1, b), NIH3T3 (c) and MDCK (d) cell lines. Figure S5. MARS-Seq library complexity assessment of fresh (red) or cryopreserved (blue) cells using the total number of detected genes. (a-d) Comparative analysis of the number of sequencing reads and detected transcripts using a linear model. The slope of the regression line was calculated separately for fresh and cryopreserved cells. Displayed are results for K562 (experiment 1, a), HEK293 (experiment 1, b), NIH3T3 (c) and MDCK (d) cell lines. Figure S6. Comparative analyses of single cell transcriptome variance from fresh (red) and cryopreserved (blue) cell lines. Gene expression variances between cells are displayed as principal component analysis (PCA, upper panel a-d) or t-distributed stochastic neighbor embedding (t-SNE, lower panel e-h) using the 100 most variable genes. The displayed experiments include K562 (experiment 1; a,e), HEK293 (experiment 1; b,f), NIH3T3 (c,g) and MDCK (d,h). Figure S7. Joint analyses of single cells from fresh (red), cryopreserved at -80ºC (blue) and cryopreserved in liquid nitrogen (green) HEK293 cells from experiment 1 (circles) and 2 (triangles). Gene expression variances between cells are displayed as principal component analysis (PCA, a) or t-distributed stochastic neighbor embedding (t-SNE, b) using the 100 most variable genes. Figure S8. Comparative analyses of single cells from fresh (red) and cryopreserved (blue) cell lines. Gene expression variances between cells are displayed as t-distributed stochastic neighbor embedding (t-SNE) using the 100 most variable genes and the indicated perplexity parameter values. The displayed experiments include K562 (experiment 1), HEK293 (experiment 1 and 2), NIH3T3 and MDCK. Figure S10. Correlation analysis of gene expression levels split by conditions (fresh (red); cryopreserved -80ºC: blue; cryopreserved liquid nitrogen: green). (a-d) Pearson’s correlation analysis between 20 randomly selected fresh and cryopreserved cells displaying the correlation coefficient (r2). (e-h) Distribution of Pearson’s correlation coefficients (r2) within and between processing conditions. The median coefficients are indicated. (i-k) Linear regression model comparing average gene expression levels of expressed genes. The coefficient of determination (r2) is displayed. Cell lines and experiments are indicated within the figures. Figure S11. Cell subtype analysis of HEK293 (experiment 1) cells split by fresh (a-c) and cryopreserved (d-f) cells. (a,d) Hierarchical clustering of single cells based on transcriptional programs (defined by gene ontology) and correlating genes [21]. Transcriptional programs and gene clusters are summarized in aspects (orange: overrepresented; green: underrepresented). Displayed are the most variable aspects (rows) and their importance (row colors). Cells are assigned to condition (fresh: red; cryopreserved: blue) and clusters. (b, e) A t-distributed stochastic neighbor embedding (t-SNE) representation of similarities between cells using previous defined distances and cluster identity (as in a, d). (c, f) Hierarchical cluster of single cells (as in a,d) displaying the 25 most variable cell cycle genes (G2/M checkpoint). Expression levels of the cell cycle signature are summarized (1st panel; orange: high, green: low) and clusters are indicated. Figure S12. Analyses of Smart-seq2-derived single cell transcriptomes from a cryopreserved patient-derived xenograft (PDOX) tumor. (a) Displayed are the sequencing read distribution following RNA library preparation of full-length transcripts. Each line represents a single cell and transcript sizes are scaled from (0-100). (b,c) Comparative analyses of single cells from fresh (circles) and cryopreserved (triangles) samples. The displayed experiments include single cells from HEK293 cells (blue), K562 cells (orange) and the PDOX (green) sample. Gene expression variances between cells are displayed as principal component analysis (PCA, b) and t-distributed stochastic neighbor embedding (t-SNE, c) using the 100 most variable genes. Figure S13. Cell subtype analysis of HEK293 cells analyzed by Smart-seq2 split by fresh (a) and 5 cryopreserved (b) cells. (a,b) Hierarchical clustering of single cells based on transcriptional programs (defined by gene ontology) and correlating genes [21] displaying the 25 most variable cell cycle genes (G2/M checkpoint). Expression levels of the cell cycle signature are summarized (1st panel; orange: high, green: low) and clusters are indicated. (c) Significantly differentially expressed genes between fresh and cryopreserved HEK293 cells (p < 0.01). Figure S14. Cell subtype analysis of K562 cells analyzed by Smart-seq2 split by fresh (a) and cryopreserved (b) cells. (a,b) Hierarchical clustering of single cells based on transcriptional programs (defined by gene ontology) and correlating genes [21] displaying the 25 most variable cell cycle genes (G2/M checkpoint). Expression levels of the cell cycle signature are summarized (1st panel; orange: high, green: low) and clusters are indicated. (c) Significantly differentially expressed genes between fresh and cryopreserved K562 cells (p < 0.01). Figure S15. Cell subtype analysis of fresh (red) and cryopreserved (blue) peripheral blood mononuclear cells analyzed by MARS-Seq. (a-d ) Hierarchical clustering of single cells based on transcriptional programs (defined by gene ontology) and correlating genes [21] (as defined in Fig. 5f) displaying the 25 most variable genes within the signatures for cytotoxic T-cells (a), memory T-cells (b), B-cells (c) and myeloid cells (d). Expression levels of all signature genes are summarized (1st panel; orange: high, green: low) and conditions (2nd panel: fresh: red; cryopreserved: blue) and clusters are indicated. The lower plots summarize the signature expression levels for each cell (dots) and cluster (box). Inferred cell types are indicated (BC: Bcells, CytoTC: cytotoxic T-cells, MemTC: memory T-cells, Myd: myeloid cells). Figure S16. Hierarchical clustering of single cells from an ovarian tumor PDOX based on the most variable genes. Cells are assigned to conditions (2nd panel; fresh: red; cryopreserved: blue) and clusters (3rd panel). Displayed are the 25 most variable genes implicated in cluster formation. Expression levels of the genes are summarized (1st panel; orange: high, green: low). (PDF 6319 kb)

Published
2017
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61. Safety evaluation of nivolumab added concurrently to radiotherapy in a standard first line chemo-RT regimen in unresectable locally advanced NSCLC: The ETOP NICOLAS phase II trial.

Author

Peters, Solange, primary, De Ruysscher, Dirk, additional, Dafni, Urania, additional, Felip, Enriqueta, additional, Guckenberger, Matthias, additional, Vansteenkiste, Johan F., additional, Huber, Rudolf M., additional, Nadal-Alforja, Ernest, additional, Irigoyen, Antonio, additional, Becker, Annemarie, additional, Piguet, Anne-Christine, additional, Kassapian, Marie, additional, Gasca-Ruchti, Adriana, additional, Martinez Marti, Alex, additional, Andratschke, Nicolaus, additional, Lambrecht, Maarten, additional, Belka, Claus, additional, Roschitzki-Voser, Heidi, additional, and Stahel, Rolf A., additional

Published
2018
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62. Activity of HSP90 Inhibiton in a Metastatic Lung Cancer Patient With a Germline BRCA1 Mutation

Author

Cedrés, Susana, primary, Felip, Enriqueta, additional, Cruz, Cristina, additional, Martinez de Castro, Ana, additional, Pardo, Nuria, additional, Navarro, Alejandro, additional, Martinez-Marti, Alex, additional, Remon, Jordin, additional, Zeron-Medina, Jorge, additional, Balmaña, Judith, additional, Llop-Guevara, Alba, additional, Miquel, Josep M, additional, Sansano, Irene, additional, Nuciforo, Paolo, additional, Mancuso, Francesco, additional, Serra, Violeta, additional, and Vivancos, Ana, additional

Published
2018
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63. Abstract A084: DENALI: a 3-arm double-blind randomized phase 2 study of carboplatin, pemetrexed, and placebo (CPP) versus carboplatin, pemetrexed, and either 1 or 2 truncated courses of demcizumab (CPD) in patients with non-squamous non-small cell lung cancer (NSCLC)

Author

Hughes, Brett, primary, Dean, Andrew, additional, Markman, Ben, additional, Dreisbach, Luke, additional, Provencio, Mariano, additional, Ciuffreda, Libero, additional, Dear, Rachel, additional, Graze, Peter, additional, Nadal, Alforia, additional, Houghton, Baerin, additional, Moran, Teresa, additional, Roberts, Rachel, additional, Dy, Grace, additional, Alvaro, Taus, additional, Martinez Marti, Alex, additional, Brachmann, Rainer, additional, Stagg, Robert, additional, and Govindan, Ramaswamy, additional

Published
2018
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64. Outcome of EGFR mutant patirnts included in a clinical trial after progression on EGFR TKI.

Author

Pardo Aranda, Nuria, primary, Remon, Jordi, additional, Martinez Marti, Alex, additional, Martinez de Castro, Ana Maria, additional, Cedres Perez, Susana, additional, Navarro, Alejandro, additional, Scheenaard, Eulalia, additional, Piera, Adelaida, additional, Carbonell, LLuisa, additional, Vivancos, Ana, additional, Felip, Enriqueta, additional, and Gámez Córdoba, Esther, additional

Published
2017
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65. Outcome of KRAS mutated (m) non-small cell lung cancer (NSCLC) patients (pts) treated with immune checkpoint inhibitors (immuneCI).

Author

Pardo Aranda, Nuria, primary, Viaplana, Cristina, additional, Remon, Jordi, additional, Martinez Marti, Alex, additional, Cedres Perez, Susana, additional, Navarro, Alejandro, additional, Martinez de Castro, Ana Maria, additional, Villacampa, Guillermo, additional, Carbonell, LLuisa, additional, Hernando, Alberto, additional, Vivancos, Ana, additional, Dienstmann, Rodrigo, additional, and Felip, Enriqueta, additional

Published
2017
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66. Single-cell transcriptome conservation in cryopreserved cells and tissues

Author

Guillaumet-Adkins, Amy, primary, Rodríguez-Esteban, Gustavo, additional, Mereu, Elisabetta, additional, Mendez-Lago, Maria, additional, Jaitin, Diego A., additional, Villanueva, Alberto, additional, Vidal, August, additional, Martinez-Marti, Alex, additional, Felip, Enriqueta, additional, Vivancos, Ana, additional, Keren-Shaul, Hadas, additional, Heath, Simon, additional, Gut, Marta, additional, Amit, Ido, additional, Gut, Ivo, additional, and Heyn, Holger, additional

Published
2017
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67. Analysis of clinical characteristics and outcomes of ALK positive (ALK+) patients treated with ALK inhibitors (ALKi).

Author

Cedres Perez, Susana, primary, Pardo Aranda, Nuria, additional, Navarro, Alejandro, additional, Martinez Marti, Alex, additional, Martinez de Castro, Ana Maria, additional, Cabrera, Guadalupe, additional, Vilaro, Marta, additional, Carbonell, LLuisa, additional, de la Fuente, Iris, additional, Piera, Adelaida, additional, Martinez, Lidia, additional, Hernandez-Losa, Javier, additional, Sansano, Irene, additional, and Felip, Enriqueta, additional

Published
2016
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68. Association of response to programmed death 1 receptor or ligand (PD1/PDL1) blockade with immune-related gene expression profiling across three cancer-types.

Author

Navarro, Alejandro, primary, Arance, Ana, additional, Reguart, Noemi, additional, Paré, Laia, additional, Galván, Patricia, additional, Martinez Marti, Alex, additional, Nuciforo, Paolo, additional, Pardo Aranda, Nuria, additional, Cedres Perez, Susana, additional, Gaba, Lydia, additional, Victoria, Iván, additional, Vinolas, Nuria, additional, Vivancos, Ana, additional, Prat, Aleix, additional, and Felip, Enriqueta, additional

Published
2016
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69. Outcome of RAS mutated lung adenocarcinoma (ADC ) patients (pts) on standard chemotherapy (chemo) and immune checkpoint inhibitors (immuneCI).

Author

Pardo Aranda, Nuria, primary, Ruiz, Fiorella, additional, Martinez Marti, Alex, additional, Navarro, Alejandro, additional, Cedres Perez, Susana, additional, de la Fuente, Iris, additional, Baste, Neus, additional, Vivancos, Ana, additional, Miquel, Josep M, additional, Dienstmann, Rodrigo, additional, and Felip, Enriqueta, additional

Published
2016
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70. Results of patients with thoracic cancers older than 70 years included in clinical trials: A center experience.

Author

Martinez Marti, Alex, primary, Cabrera, Guadalupe, additional, Ortiz, Carolina, additional, Vilaro, Marta, additional, Miquel, Josep M, additional, Cedres Perez, Susana, additional, Navarro, Alejandro, additional, Pardo Aranda, Nuria, additional, Martinez, Pablo, additional, Piera, Adelaida, additional, Carbonell, LLuisa, additional, De la Fuente, Iris, additional, Garcia, Silvia, additional, Sansano, Irene, additional, and Felip, Enriqueta, additional

Published
2016
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71. Analysis of RSPO gene expression in solid tumors.

Author

Vivancos, Ana, primary, Palmer, Hector G., additional, Ogbah, Zighereda, additional, Matito, Judit, additional, Mancuso, Francesco M, additional, Navarro, Alejandro, additional, Martinez Marti, Alex, additional, Argiles, Guillem, additional, Elez, Elena, additional, Rodón, Jordi, additional, Nuciforo, Paolo, additional, Tabernero, Josep, additional, and Felip, Enriqueta, additional

Published
2016
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74. Association of peripheral memory B cell population maintenance and long term survival after perioperative chemoimmunotherapy in NSCLC (NADIM trial).

Author

Sierra-Rodero, Belen, Cruz Bermudez, Alberto, Martinez-Toledo, Cristina, Molina-Alejandre, Marta, García-Grande, Aránzazu, Calvo, Virginia, Nadal, Ernest, Campelo, Rosario Garcia, Insa, Amelia, Domine, Manuel, Massuti, Bartomeu, Garrido, Alberto, Majem, Margarita, Martinez-Marti, Alex, de Castro Carpeño, Javier, Rodriguez-Abreu, Delvys, Cobo, Manuel, Barneto, Isidoro, Viteri, Santiago, and Provencio-Pulla, Mariano

Published
2023
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75. IMpower010: Exploratory analysis of disease-free survival by KRAS status in patients with stage II-IIIA NSCLC treated with adjuvant atezolizumab vs best supportive care.

Author

Reck, Martin, Srivastava, Minu K, Wakelee, Heather A., Felip, Enriqueta, Altorki, Nasser K., Csoszi, Tibor, Moiseyenko, Vladimir, Akopov, Andrey, Smolin, Alexey, Chella, Antonio, Vallieres, Eric, Martinez-Marti, Alex, Zou, Wei, McNally, V., Bennett, Elizabeth, Prizant, Hen, Nabet, Barzin, Ballinger, Marcus, Gitlitz, Barbara J., and Zhou, Caicun

Published
2023
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76. Concordance of PD-L1 expression by different immunohistochemistry (IHC) definitions and in situ hybridization (ISH) in squamous cell carcinoma (SCC) of the lung.

Author

Martinez Marti, Alex, primary, Martinez, Pablo, additional, Navarro, Alejandro, additional, Cedres, Susana, additional, Murtra-Garrell, Nuria, additional, Salva, Francesc, additional, Sansano, Irene, additional, Romero, Laura, additional, Felip, Enriqueta, additional, and Nuciforo, Paolo, additional

Published
2014
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77. The HALO study: A phase I-II of the oral HSP90 inhibitor Debio0932 in combination with SOC in first- and second-line therapy of advanced NSCLC.

Author

Corral Jaime, Jesus, primary, Paz-Ares, Luis, additional, Provencio, Mariano, additional, Bennouna, Jaafar, additional, Ponce-Aix, Santiago, additional, Plummer, Ruth, additional, Delord, Jean-Pierre, additional, Isambert, Nicolas, additional, Trigo, Jose Manuel, additional, Belli, Riccardo, additional, Brienza, Silvano, additional, Zanna, Claudio, additional, Purcea, Daniela, additional, Calvo, Virginia, additional, Alonso, Miriam, additional, Senellart, Hélène, additional, Hiret, Sandrine, additional, Martinez Marti, Alex, additional, and Felip, Enriqueta, additional

Published
2014
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79. Fluorescence In Situ Hybridization and Immunohistochemistry as Diagnostic Methods for ALK Positive Non-Small Cell Lung Cancer Patients

Author

Martinez, Pablo, Hernandez-Losa, Javier, Cedrés, Susana, Castellvi, Josep, Martinez-Marti, Alex, Tallada, Natalia, Murtra-Garrell, Nuria, Navarro, Alejandro, Rodriguez-Freixinos, Victor, Canela, Mercedes, Ramon y Cajal, Santiago, Felip, Enriqueta, Universitat Autònoma de Barcelona, Martinez, Pablo, Hernandez-Losa, Javier, Cedrés, Susana, Castellvi, Josep, Martinez-Marti, Alex, Tallada, Natalia, Murtra-Garrell, Nuria, Navarro, Alejandro, Rodriguez-Freixinos, Victor, Canela, Mercedes, Ramon y Cajal, Santiago, Felip, Enriqueta, and Universitat Autònoma de Barcelona

Abstract

Anaplastic Lymphoma Kinase (ALK) positivity represents a novel molecular target in a subset of Non-Small Cell Lung Cancers (NSCLC). We explore Fluorescence in situ Hybridization (FISH) and Immunohistochemistry (IHC) as diagnostic methods for ALK positive patients and to describe its prevalence and outcomes in a population of NSCLC patients. NSCLC patients previously screened for Epidermal Growth Factor Receptor (EGFR) at our institution were selected. ALK positive patients were identified by FISH and the value of IHC (D5F3) was explored. ninety-nine patients were identified. Median age was 61.5 years (range 35-83), all were caucasians, eighty percent were adenocarcinomas, fifty-one percent were male and thirty-eight percent were current smokers. Seven (7.1%) patients were ALK positive by FISH, thirteen (13.1%) were EGFR mutant, and 65 (65.6%) were negative/Wild Type (WT) for both ALK and EGFR. ALK positivity and EGFR mutations were mutually exclusive. ALK positive patients tend to be younger than EGFR mutated or wt patients. ALK positive patients were predominantly never smokers (71.4%) and adenocarcinoma (71.4%). ALK positive and EGFR mutant patients have a better outcome than negative/WT. All patients with ALK FISH negative tumours were negative for ALK IHC. Out of 6 patients positive for ALK FISH with more tissue available, 5 were positive for ALK IHC and 1 negative. ALK positive patients represent 7.1% of a population of selected NSCLC. ALK positive patients have different clinical features and a better outcome than EGFR WT and ALK negative patients. IHC is a promising method for detecting ALK positive NSCLC patients

Published
2013

80. Phase IB study of olaparib (AZD2281) plus gefitinib in EGFR-mutant patients (p) with advanced non-small-cell lung cancer (NSCLC) (NCT01513174/GECP-GOAL).

Author

García Campelo, Rosario, primary, Felip, Enriqueta, additional, Massuti, Bartomeu, additional, Majem, Margarita, additional, Carcereny, Enric, additional, Cardenal, Felipe, additional, Molina-Vila, Miguel Angel, additional, Martinez Marti, Alex, additional, Marti-Ciriquian, Juan Luis, additional, Alonso-Jaudenes Curbera, Guillermo, additional, Pallares, Cinta, additional, Palmero, Ramon, additional, Gonzalez-Arenas, Maria Carmen, additional, Mayo-de las Casas, Clara, additional, Sanchez-Ronco, Maria, additional, and Rosell, Rafael, additional

Published
2013
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81. Whole-exome sequencing in tumor samples from sequenom-wild-type, ALK negative stage IV lung adenocarcinoma (ADC) patients (p).

Author

Felip, Enriqueta, primary, Caratu, Ginevra, additional, Silberschmidt, Daniel, additional, Martinez, Pablo, additional, Martinez Marti, Alex, additional, Cedres, Susana, additional, Murtra-Garrell, Nuria, additional, Navarro-Mendivil, Alejandro, additional, Prudkin, Ludmila, additional, Jimenez, Jose, additional, de la Morena, Pilar, additional, Canela, Mercedes, additional, Nuciforo, Paolo, additional, Palmer, Hector G., additional, and Vivancos, Ana, additional

Published
2013
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83. Amplification of fibroblast growth factor receptor type 1 gene (FGFR1) in samples from 101 NSCLC patients (pts) with squamous cell carcinoma (SCC) histology.

Author

Martinez Marti, Alex, primary, Martinez, Pablo, additional, Aura, Claudia, additional, Cedres, Susana, additional, Sullivan, Ivana, additional, Jimenez, Jose, additional, Prudkin, Ludmila, additional, Montero, Maria Angeles, additional, Murtra-Garrell, Nuria, additional, Zamora, Esther, additional, Navarro, Alejandro, additional, Hernandez-Losa, Javier, additional, Salcedo, Maite, additional, Canela, Mercedes, additional, Ramon y Cajal, Santiago, additional, Tabernero, Josep, additional, and Felip, Enriqueta, additional

Published
2012
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84. Skin toxicity associated with outcome to erlotinib in non-small cell lung cancer (NSCLC) patients (p) with EGFR mutations in the EURTAC study.

Author

Buges, Cristina, primary, Martinez Marti, Alex, additional, Rosell, Rafael, additional, Vergnenegre, Alain, additional, De Marinis, Filippo, additional, Massuti, Bartomeu, additional, De Castro, Javier, additional, Gervais, Radj, additional, Carcereny Costa, Enric, additional, Moran, Teresa, additional, Santarpia, Mariacarmela, additional, Felip, Enriqueta, additional, Majem, Margarita, additional, Porta, Rut, additional, Palmero, Ramon, additional, Drozdowskyj, Ana, additional, Heidecke, Cordula, additional, Gasco, Amaya, additional, Taron, Miquel, additional, and Paz-Ares, Luis G., additional

Published
2012
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85. Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial.

Author

O'Brien, Mary, Paz-Ares, Luis, Marreaud, Sandrine, Dafni, Urania, Oselin, Kersti, Havel, Libor, Esteban, Emilio, Isla, Dolores, Martinez-Marti, Alex, Faehling, Martin, Tsuboi, Masahiro, Lee, Jong-Seok, Nakagawa, Kazuhiko, Yang, Jing, Samkari, Ayman, Keller, Steven M, Mauer, Murielle, Jha, Nitish, Stahel, Rolf, and Besse, Benjamin

Subjects
*CLINICAL trials, *NON-small-cell lung carcinoma, *CARDIOGENIC shock, *PLACEBOS, *PROGRESSION-free survival, *ADVERSE health care events
Abstract

Background: Pembrolizumab is a standard-of-care for advanced non-small-cell lung cancer (NSCLC). We assessed pembrolizumab as adjuvant therapy for completely resected stage IB-IIIA NSCLC.Methods: In this randomised, triple-blind, phase 3 trial (PEARLS/KEYNOTE-091), patients were recruited from 196 medical centres in 29 countries. Eligible patients were aged 18 years or older, with completely resected, pathologically confirmed stage IB (tumours of ≥4 cm in diameter), II, or IIIA NSCLC per the American Joint Committee on Cancer staging system (7th edition) of any histology or PD-L1 expression level, and an Eastern Cooperative Oncology Group performance status of 0 or 1; adjuvant chemotherapy was to be considered for stage IB disease and was strongly recommended for stage II and IIIA disease, according to national and local guidelines. Using a central interactive voice-response system, eligible participants were randomly assigned (1:1), using a minimisation technique and stratified by disease stage, previous adjuvant chemotherapy, PD-L1 expression, and geographical region, to pembrolizumab 200 mg or placebo, both administered intravenously every 3 weeks for up to 18 cycles. Participants, investigators, and analysts were masked to treatment assignment. Dual primary endpoints were disease-free survival in the overall population and in the population with PD-L1 tumour proportion score (TPS) of 50% or greater. Efficacy was assessed in the intention-to-treat (ITT) population (ie, all participants randomly assigned to a treatment group). Safety was assessed in all participants randomly assigned to treatment who received at least one dose of study treatment. Here we report results of the second interim analysis, prespecified to occur when approximately 118 disease-free survival events had occurred in the PD-L1 TPS of 50% or greater population. This study is registered with ClinicalTrials.gov, NCT02504372, and is active but not recruiting.Findings: Between Jan 20, 2016, and May 6, 2020, 1177 (60%) of 1955 screened participants were randomly assigned to pembrolizumab (n=590, including n=168 with PD-L1 TPS of ≥50%) or placebo (n=587; including n=165 with PD-L1 TPS of ≥50%) and included in the ITT population. Median follow-up as of data cutoff (Sept 20, 2021) for this interim analysis was 35·6 months (IQR 27·1-45·5). In the overall population, median disease-free survival was 53·6 months (95% CI 39·2 to not reached) in the pembrolizumab group versus 42·0 months (31·3 to not reached) in the placebo group (HR 0·76 [95% CI 0·63-0·91], p=0·0014). In the PD-L1 TPS of 50% or greater population, median disease-free survival was not reached in either the pembrolizumab group (95% CI 44·3 to not reached) or the placebo group (95% CI 35·8 to not reached; HR 0·82 [95% CI 0·57-1·18]; p=0·14). Grade 3 or worse adverse events occurred in 198 (34%) of 580 participants who received pembrolizumab and 150 (26%) of 581 participants who received placebo. Grade 3 or worse events that occurred in at least ten participants in either treatment group were hypertension (35 [6%]) and pneumonia (12 [2%]) with pembrolizumab and hypertension (32 [6%]) with placebo. Serious adverse events occurred in 142 (24%) participants in the pembrolizumab group and 90 (15%) in the placebo group; serious adverse events that occurred in more than 1% of participants were pneumonia (13 [2%]), pneumonitis (12 [2%]), and diarrhoea (seven [1%]) with pembrolizumab and pneumonia (nine [2%]) with placebo. Treatment-related adverse events led to death in four (1%) participants treated with pembrolizumab (one due to both cardiogenic shock and myocarditis, one due to both septic shock and myocarditis, one due to pneumonia, and one due to sudden death) and in no participants treated with placebo.Interpretation: Pembrolizumab significantly improved disease-free survival compared with placebo and was not associated with new safety signals in completely resected, PD-L1-unselected, stage IB-IIIA NSCLC. Pembrolizumab is potentially a new treatment option for stage IB-IIIA NSCLC after complete resection and, when recommended, adjuvant chemotherapy, regardless of PD-L1 expression.Funding: Merck Sharp & Dohme, a subsidiary of Merck & Co. [ABSTRACT FROM AUTHOR]

Published
2022
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86. Activity of HSP90 Inhibiton in a Metastatic Lung Cancer Patient With a Germline BRCA1 Mutation.

Author

Cedrés S, Felip E, Cruz C, Martinez de Castro A, Pardo N, Navarro A, Martinez-Marti A, Remon J, Zeron-Medina J, Balmaña J, Llop-Guevara A, Miquel JM, Sansano I, Nuciforo P, Mancuso F, Serra V, and Vivancos A

Subjects
Adult, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Breast Neoplasms pathology, Carcinoma, Ductal, Breast drug therapy, Carcinoma, Ductal, Breast genetics, Carcinoma, Ductal, Breast pathology, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung secondary, Cisplatin administration & dosage, Deoxycytidine administration & dosage, Deoxycytidine analogs & derivatives, Female, Humans, Lung Neoplasms genetics, Lung Neoplasms secondary, Maintenance Chemotherapy, Treatment Outcome, Gemcitabine, Antineoplastic Combined Chemotherapy Protocols therapeutic use, BRCA1 Protein genetics, Carcinoma, Non-Small-Cell Lung drug therapy, Germ-Line Mutation, HSP90 Heat-Shock Proteins antagonists & inhibitors, Isoxazoles administration & dosage, Lung Neoplasms drug therapy, Resorcinols administration & dosage
Abstract

Heat shock proteins (HSPs) are molecular chaperones that maintain proteins in their correct conformation to ensure stability and protect carcinoma cells from apoptosis. HSP90 inhibitors (HSP90i) block multiple targets simultaneously, and despite responses in a selected population, no HSP90i have yet been approved. We present a patient with a lung tumor with an exceptional response to cisplatin/gemcitabine in combination with HSP90i, which nowadays continues with HSP90i maintenance after three years. Whole-exome sequencing of the lung tumor unveiled a BRCA1/2 deficiency mutational signature, and mutation analysis confirmed a germline BRCA1 mutation. The striking efficacy of HSP90i plus chemotherapy vs chemotherapy alone was reproduced in a patient-derived xenograft (PDX) model from a breast cancer patient with a BRCA1 mutation (mean tumor volume [SD], No. of tumors: vehicle 8.38 [7.07] mm3, n = 3; HSP90i 4.18 [1.93] mm3, n = 5; cisplatin plus gemcitabine 3.31 [1.95] mm3, n = 5; cisplatin plus gemcitabine plus HSP90i 0.065 [0.076] mm3, n = 6). This case and the PDX demonstrate the efficacy for therapeutic inhibition of HSP90 in a BRCA-mutated patient, opening a new potential avenue for better identifying patients who might benefit most from HSP90i.

Published
2018
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87. Fluorescence in situ hybridization and immunohistochemistry as diagnostic methods for ALK positive non-small cell lung cancer patients.

Author

Martinez P, Hernández-Losa J, Montero MÁ, Cedrés S, Castellví J, Martinez-Marti A, Tallada N, Murtra-Garrell N, Navarro-Mendivill A, Rodriguez-Freixinos V, Canela M, Ramon y Cajal S, and Felip E

Subjects
Adult, Aged, Aged, 80 and over, Anaplastic Lymphoma Kinase, Carcinoma, Non-Small-Cell Lung enzymology, Female, Humans, Lung Neoplasms enzymology, Male, Middle Aged, Carcinoma, Non-Small-Cell Lung diagnosis, Immunohistochemistry methods, In Situ Hybridization, Fluorescence methods, Lung Neoplasms diagnosis, Receptor Protein-Tyrosine Kinases metabolism
Abstract

Background: Anaplastic Lymphoma Kinase (ALK) positivity represents a novel molecular target in a subset of Non-Small Cell Lung Cancers (NSCLC). We explore Fluorescence in situ Hybridization (FISH) and Immunohistochemistry (IHC) as diagnostic methods for ALK positive patients and to describe its prevalence and outcomes in a population of NSCLC patients., Methods: NSCLC patients previously screened for Epidermal Growth Factor Receptor (EGFR) at our institution were selected. ALK positive patients were identified by FISH and the value of IHC (D5F3) was explored., Results: ninety-nine patients were identified. Median age was 61.5 years (range 35-83), all were caucasians, eighty percent were adenocarcinomas, fifty-one percent were male and thirty-eight percent were current smokers. Seven (7.1%) patients were ALK positive by FISH, thirteen (13.1%) were EGFR mutant, and 65 (65.6%) were negative/Wild Type (WT) for both ALK and EGFR. ALK positivity and EGFR mutations were mutually exclusive. ALK positive patients tend to be younger than EGFR mutated or wt patients. ALK positive patients were predominantly never smokers (71.4%) and adenocarcinoma (71.4%). ALK positive and EGFR mutant patients have a better outcome than negative/WT. All patients with ALK FISH negative tumours were negative for ALK IHC. Out of 6 patients positive for ALK FISH with more tissue available, 5 were positive for ALK IHC and 1 negative., Conclusions: ALK positive patients represent 7.1% of a population of selected NSCLC. ALK positive patients have different clinical features and a better outcome than EGFR WT and ALK negative patients. IHC is a promising method for detecting ALK positive NSCLC patients.

Published
2013
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