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229 results on '"Summers, Y."'

4. MA06.06 A Phase II Trial of Ceralasertib and Durvalumab in Advanced Non-Small Cell Lung Cancer (NSCLC) with and without RAS Mutations: Results of NLMT Arm J

Author

Middleton, G., primary, Fletcher, P., additional, Savage, J., additional, Mehmi, M., additional, Greystoke, A., additional, Dangoor, A., additional, Cave, J., additional, Escriu, C., additional, Shaw, P., additional, Steele, N., additional, Jain, P., additional, Popat, S., additional, Forster, M., additional, Spicer, J., additional, Coupe, N., additional, Danson, S., additional, Gilligan, D., additional, Muthukumar, D., additional, Price, G., additional, Summers, Y., additional, Toy, E., additional, and Billingham, L., additional

Published
2023
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5. PL03.10 MARS 2: A Multicentre Randomised Trial Comparing (Extended) Pleurectomy Decortication versus No Radical Surgery for Mesothelioma

Author

Lim, E., primary, Waller, D., additional, Lau, K., additional, Steele, J., additional, Pope, A., additional, Ali, C., additional, Bilancia, R., additional, Keni, M., additional, Popat, S., additional, O'Brien, M., additional, Tokaca, N., additional, Maskell, N., additional, Stadon, L., additional, Nakas, A., additional, Fennell, D., additional, Edwards, J., additional, Tenconi, S., additional, Socci, L., additional, Rintoul, R., additional, Wood, K., additional, Stone, A., additional, Muthukumar, D., additional, Ingle, C., additional, Taylor, P., additional, Cove-Smith, L., additional, Califano, R., additional, Summers, Y., additional, Tasigiannopoulos, Z., additional, Bille, A., additional, Shah, R., additional, Fuller, L., additional, Shamash, J., additional, Macnair, A., additional, Mansy, T., additional, Milton, R., additional, Koh, P., additional, Ionescu, A.A., additional, Treece, S., additional, Roy, A., additional, Middleton, G., additional, Kirk, A., additional, Harris, R., additional, Ashton, K., additional, Warnes, B., additional, Bridgeman, E., additional, Joyce, K., additional, Mills, N., additional, Elliott, D., additional, Farrar, N., additional, Stokes, E., additional, Hughes, V., additional, Nicholson, A., additional, and Rogers, C., additional

Published
2023
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7. The evolution of lung cancer and impact of subclonal selection in TRACERx

Author

Frankell, A.M., Dietzen, M., Al Bakir, M., Lim, E.L., Karasaki, T., Ward, S., Veeriah, S., Colliver, E., Huebner, A., Bunkum, A., Hill, M.S., Grigoriadis, K., Moore, D.A., Black, J.R.M., Liu, W.K., Thol, K., Pich, O., Watkins, T.B.K., Naceur-Lombardelli, C., Cook, D.E., Salgado, R., Wilson, G.A., Bailey, C., Angelova, M., Bentham, R., Martínez-Ruiz, C., Abbosh, C., Nicholson, A.G., Le Quesne, J., Biswas, D., Rosenthal, R., Puttick, C., Hessey, S., Lee, C., Prymas, P., Toncheva, A., Smith, J., Xing, W., Nicod, J., Price, G., Kerr, K.M., Naidu, B., Middleton, G., Blyth, K.G., Fennell, D.A., Forster, M.D., Lee, S.M., Falzon, M., Hewish, M., Shackcloth, M.J., Lim, E., Benafif, S., Russell, P., Boleti, E., Krebs, M.G., Lester, J.F., Papadatos-Pastos, D., Ahmad, T., Thakrar, R.M., Lawrence, D., Navani, N., Janes, S.M., Dive, C., Blackhall, F.H, Summers, Y., Cave, J., Marafioti, T., Herrero, J., Quezada, S.A., Peggs, K.S., Schwarz, R.F., Van Loo, P., Miedema, D.M., Birkbak, N.J., Hiley, C.T., Hackshaw, A., Zaccaria, S., Jamal-Hanjani, M., McGranahan, N., and Swanton, C.

Subjects
Cancer Research
Abstract

Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource.

Published
2023

8. Correlation between treatment effects on response rate and progression-free survival and overall survival in trials of targeted therapies in molecularly enriched populations

Author

Solomon, BJ, Loong, HH, Summers, Y, Thomas, ZM, French, P, Lin, BK, Sashegyi, A, Wolf, J, Yang, JC-H, Drilon, A, Solomon, BJ, Loong, HH, Summers, Y, Thomas, ZM, French, P, Lin, BK, Sashegyi, A, Wolf, J, Yang, JC-H, and Drilon, A

Abstract

BACKGROUND: The number of randomized trials of agents targeting oncogene-addicted tumors has surged in the past 10 years. Using a meta-analysis, we explored whether improvements in objective response rate (ORR) in comparative trials using targeted agents could serve as a potential surrogate endpoint for improvements in progression-free survival (PFS) or overall survival (OS) in populations with oncogene-addicted cancer. PATIENTS AND METHODS: Using commercial text mining software I2E, we searched ClinicalTrials.gov and MEDLINE databases for randomized, phase III trials based on prospectively defined criteria, including (i) use of agents targeting EGFR activating mutations, ALK rearrangements, BRAF V600E or V600K mutations, and BCR-ABL fusion protein; (ii) molecularly enriched trial population or subpopulation; (iii) control arm only randomized to chemo/cytotoxic therapy. Correlative analyses were performed using ORR, OS, and PFS data from trials that met these criteria. RESULTS: A total of 62 trials were identified; 15 met all of the prespecified criteria. The ORR effect size (both the difference in ORR between arms and the log odds ratio) and log PFS hazard ratio were strongly correlated: -0.78 (P = 0.0007) for the ORR difference model; -0.74 (P = 0.0017) for the log odds ratio model. ORR effect size was positively correlated with the log OS hazard ratio, but more weakly: -0.67 (P = 0.013) for the ORR difference model and -0.58 (P = 0.036) for the log odds ratio model. Analysis of the treatment effects between OS and PFS found no correlation. CONCLUSIONS: These analyses identified a strong correlation between treatment effects on ORR and PFS in randomized clinical trials investigating agents targeting oncogene-driven cancers. A weaker correlation was observed between ORR and OS. These meta-analysis results support the use of a high ORR forming the basis of an initial regulatory approval in biomarker-driven studies.

Published
2022

9. Correlation between treatment effects on response rate and progression-free survival and overall survival in trials of targeted therapies in molecularly enriched populations

Author

Solomon, B. J., Loong, H. H., Summers, Y., Thomas, Z. M., French, P., Lin, B. K., Sashegyi, A., Wolf, J., Yang, J. C-H, Drilon, A., Solomon, B. J., Loong, H. H., Summers, Y., Thomas, Z. M., French, P., Lin, B. K., Sashegyi, A., Wolf, J., Yang, J. C-H, and Drilon, A.

Abstract

Background: The number of randomized trials of agents targeting oncogene-addicted tumors has surged in the past 10 years. Using a meta-analysis, we explored whether improvements in objective response rate (ORR) in comparative trials using targeted agents could serve as a potential surrogate endpoint for improvements in progression-free survival (PFS) or overall survival (OS) in populations with oncogene-addicted cancer. Patients and methods: Using commercial text mining software I2E, we searched ClinicalTrials.gov and MEDLINE databases for randomized, phase III trials based on prospectively defined criteria, including (i) use of agents targeting EGFR activating mutations, ALK rearrangements, BRAF V600E or V600K mutations, and BCR-ABL fusion protein; (ii) molecularly enriched trial population or subpopulation; (iii) control arm only randomized to chemo/ cytotoxic therapy. Correlative analyses were performed using ORR, OS, and PFS data from trials that met these criteria. Results: A total of 62 trials were identified; 15 met all of the prespecified criteria. The ORR effect size (both the difference in ORR between arms and the log odds ratio) and log PFS hazard ratio were strongly correlated: -0.78 (P = 0.0007) for the ORR difference model; -0.74 (P = 0.0017) for the log odds ratio model. ORR effect size was positively correlated with the log OS hazard ratio, but more weakly: -0.67 (P = 0.013) for the ORR difference model and -0.58 (P = 0.036) for the log odds ratio model. Analysis of the treatment effects between OS and PFS found no correlation. Conclusions: These analyses identified a strong correlation between treatment effects on ORR and PFS in randomized clinical trials investigating agents targeting oncogene-driven cancers. A weaker correlation was observed between ORR and OS. These meta-analysis results support the use of a high ORR forming the basis of an initial regulatory approval in biomarker-driven studies.

Published
2022

12. 115P Survival data from EMPOWER-Lung 4: Phase II study of cemiplimab plus ipilimumab in the second-line (2L) treatment of advanced non-small cell lung cancer (NSCLC)

Author

Shim, B.Y., primary, Lee, S., additional, Carpeño, J. de Castro, additional, Chiu, C-H., additional, Cobo, M., additional, Kim, H.R., additional, Ryu, J.S., additional, Tarruella, M. Majem, additional, Summers, Y., additional, Thomas, C.A., additional, Xu, Y., additional, Lowy, I., additional, and Rietschel, P., additional

Published
2021
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13. 1269P EMPOWER-lung 4: Phase II, randomized, open-label high dose or standard dose cemiplimab alone/plus ipilimumab in the second-line treatment of advanced non-small cell lung cancer (NSCLC)

Author

Shim, B.Y., primary, Lee, S., additional, de Castro Carpeño, J., additional, Chiu, C-H., additional, Cobo, M., additional, Kim, H.R., additional, Ryu, J.S., additional, Tarruella, M.M., additional, Summers, Y., additional, Thomas, C.A., additional, Xu, Y., additional, Lowy, I., additional, and Rietschel, P., additional

Published
2020
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14. 108P Pembrolizumab in pre-treated advanced non-small cell lung cancer (NSCLC) patients (pts): Impact of blood-based biomarkers on survival outcomes

Author

Ortega Franco, A., primary, Tay, R., additional, Raja, H., additional, Ackermann, C.J., additional, Carter, M., additional, Lindsay, C., additional, Hughes, S., additional, Cove-Smith, L., additional, Taylor, P., additional, Summers, Y., additional, Blackhall, F.H., additional, and Califano, R., additional

Published
2020
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16. Pneumocystis jirovecii pneumonia (PJP) prophylaxis in lung cancer patients receiving radical radiotherapy (RT) ± chemotherapy (CTRT): audit of the first UK departmental guideline

Author

Beech, A., primary, Faivre-Finn, C., additional, Bayman, N., additional, Blackhall, F., additional, Califano, R., additional, Chan, C., additional, Cobben, D., additional, Coote, J., additional, Cove-Smith, L., additional, Harris, M., additional, Hughes, S., additional, Martimarti, F., additional, Pemberton, L., additional, Salem, A., additional, Summers, Y., additional, Taylor, P., additional, Wang, X., additional, Woolf, D., additional, and Sheikh, H., additional

Published
2020
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19. PL02.09 National Lung Matrix Trial (NLMT): First Results from an Umbrella Phase II Trial in Advanced Non-Small Cell Lung Cancer (NSCLC)

Author

Middleton, G., primary, Popat, S., additional, Fletcher, P., additional, Summers, Y., additional, Greystoke, A., additional, Gilligan, D., additional, Cave, J., additional, O'Rourke, N., additional, Brewster, A., additional, Toy, E., additional, Spicer, J., additional, Savage, J., additional, Sharpe, R., additional, Yap, T., additional, Swanton, C., additional, and Billingham, L., additional

Published
2019
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21. Brigatinib experience on the ALK project

Author

Gomes, F., primary, Tokaca, N., additional, Yip, K., additional, Ghosh, S., additional, Newsom-Davis, T., additional, Greystoke, A., additional, Mills, H., additional, Ahmed, S., additional, Harle, A.S., additional, Ayre, G., additional, Shah, R., additional, Popat, S., additional, Blackhall, F.H., additional, and Summers, Y., additional

Published
2019
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23. The ALK project: a real-world national network and database

Author

Gomes, F., primary, Yip, K., additional, Tokaca, N., additional, Greystoke, A., additional, Escriu, C., additional, Conibear, J., additional, Ghosh, S., additional, Doherty, G.J., additional, Funingana, I., additional, Ahmad, T., additional, Ahmed, S., additional, Cox, R.A., additional, Newsom-Davis, T., additional, Mills, H., additional, Shah, R., additional, Dorey, N., additional, Harle, A., additional, Dancey, G., additional, Baijal, S., additional, Geldart, T., additional, Ghafoor, Q., additional, Tarver, K., additional, Talbot, T., additional, Forster, M., additional, Cove-Smith, L., additional, Califano, R., additional, Blackhall, F., additional, Popat, S., additional, and Summers, Y., additional

Published
2019
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25. Real-world outcomes with pembrolizumab in patients with treatment-naive advanced/metastatic NSCLC in the UK: multicentre retrospective observational study

Author

Tokaca, N., primary, Gomes, F., additional, Lau, S., additional, Jackson, A., additional, Gradwell, M., additional, Gyi, M., additional, Reinius, M., additional, Valentine, E., additional, Winn, E., additional, Bhosle, J., additional, O’Brien, M., additional, Yousaf, N., additional, Blackhall, F., additional, Gilligan, D., additional, Treece, S., additional, Yip, K., additional, Geldart, T., additional, Baluch, S., additional, Gulliford, T., additional, Muthuramalingam, S., additional, Dancey, G., additional, Britten, A., additional, Brock, J., additional, Stokoe, J., additional, Jain, P., additional, Franks, K., additional, Toy, E., additional, Newsom-Davis, T., additional, Khan, O., additional, Greystoke, A., additional, Ali, C., additional, Leonard, P., additional, Summers, Y., additional, and Popat, S., additional

Published
2019
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26. Multi-modality radical intent treatment in synchronous oligometastatic non-small cell lung cancer: how many patients complete the full treatment regime recommended by the MDT?

Author

Cheng, A., primary, Craig, C., additional, Summers, Y., additional, Taylor, P., additional, Califano, R., additional, Cove-Smith, L., additional, Woolf, D., additional, Duerden, R., additional, Sharman, A., additional, Lyons, J., additional, Crosbie, P.A.J., additional, Booton, R., additional, and Evison, M., additional

Published
2019
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28. Randomized Phase III Trial of Erlotinib versus Docetaxel in Patients with Advanced Squamous Cell Non-Small Cell Lung Cancer Failing First-Line Platinum-Based Doublet Chemotherapy Stratified by VeriStrat Good versus VeriStrat Poor. The European Thoracic Oncology Platform (ETOP) EMPHASIS-lung Trial

Author

Peters S, Stahel RA, Dafni U, Ponce Aix S, Massutí B, Gautschi O, Coate L, López Martín A, van Heemst R, Berghmans T, Meldgaard P, Cobo Dols M, Garde Noguera J, Curioni-Fontecedro A, Rauch D, Mark MT, Cuffe S, Biesma B, van Henten AMJ, Juan Vidal Ó, Palmero Sanchez R, Villa Guzmán JC, Collado Martin R, Peralta S, Insa A, Summers Y, Láng I, Horgan A, Ciardiello F, de Hosson S, Pieterman R, Groen HJM, van den Berg PM, Zielinski CC, Chittazhathu Kurian Kuruvilla Y, Gasca-Ruchti A, Kassapian M, Novello S, Torri V, Tsourti Z, Gregorc V, Smit EF, EMPHASIS-lung Collaborative Group, Pulmonary medicine, CCA - Cancer Treatment and quality of life, Peters, S, Stahel, Ra, Dafni, U, Aix, Sp, Massutí, B, Gautschi, O, Coate, L, López Martín, A, Van Heemst, R, Berghmans, T, Meldgaard, P, Cobo Dols, M, Noguera, Jg, Curioni Fontecedro, A, Rauch, D, Mark, Mt, Cuffe, S, Biesma, B, Van Henten, Am, Vidal, Ój, Sanchez, Rp, Villa Guzmán, Jc, Martin, Rc, Peralta, S, Insa, A, Summers, Y, Láng, I, Horgan, A, Ciardiello, Fortunato, De Hosson, S, Pieterman, R, Groen, Hj, Van Den Berg, Pm, Zielinski, Cc, Kuruvilla, Yc, Gasca Ruchti, A, Kassapian, M, Novello, S, Torri, V, Tsourti, Z, Gregorc, V, Smit, Ef, and EMPHASIS lung collaborative, Group

Subjects
Oncology, Male, Lung Neoplasms, medicine.medical_treatment, Docetaxel, NSCLC, THERAPY, Squamous, Cohort Studies, RETROSPECTIVE ANALYSIS, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, 3RD-LINE, Antineoplastic Combined Chemotherapy Protocols, VeriStrat, 030212 general & internal medicine, Erlotinib Hydrochloride, ETOP, Prognosis, Survival Rate, Erlotinib, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Female, Taxoids, Veristrat, 2ND-LINE TREATMENT, medicine.drug, Pulmonary and Respiratory Medicine, medicine.medical_specialty, 03 medical and health sciences, Internal medicine, Multicenter trial, medicine, TYROSINE KINASE INHIBITORS, Journal Article, Humans, Lung cancer, COMBINATION, Survival rate, neoplasms, METAANALYSIS, Aged, Neoplasm Staging, Platinum, Chemotherapy, business.industry, medicine.disease, respiratory tract diseases, business, GROWTH-FACTOR RECEPTOR, Follow-Up Studies
Abstract

Introduction: Docetaxel and erlotinib are registered second line treatments for wild-type EGFR NSCLC. Previous studies suggested a predictive value of the VeriStrat test in second line therapy of NSCLC, classifying patients as either VeriStrat good or VeriStrat poor. EMPHASIS-lung aimed at exploring this predictive effect in patients with squamous cell NSCLC. The trial closed prematurely because of low accrual and results from other trials. Our analysis includes an exploratory combined analysis with results from the PROSE trial.Methods: EMPHASIS-lung was a randomized phase III multicenter trial exploring the differential effect of second line erlotinib versus docetaxel on progression-free survival (PFS) in VeriStrat good versus VeriStrat poor patients with squamous cell NSCLC.Results: A total of 80 patients were randomized, with 72.5% categorized as VeriStrat good. Patient characteristics were balanced between VeriStrat status and treatment groups. The median PFS times with docetaxel and erlotinib treatment in the VeriStrat good cohort were 4.1 and 1.6 months, respectively, versus 1.9 and 2.1 months, respectively, in the VeriStrat poor cohort. The median overall survival (OS) times with docetaxel and erlotinib treatment in the VeriStrat good cohort were 7.8 and 8.4 months, respectively, and 4.4 and 5.2 months, respectively, in the VeriStrat poor cohort. An additional exploratory analysis was performed; in it, 47 patients from the squamous cell subgroup of PROSE were included in a combined analysis, contributing with 45 PFS and 41 OS events.Conclusions: The final analysis of EMPHASIS-lung did not show a differential effect on PFS for erlotinib versus docetaxel stratified by VeriStrat status. Similarly, in the combined analysis, no significant treatment by VeriStrat status interaction was observed (interaction p=0.24 for PFS and 0.45 for OS, stratified by study). (C) 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Published
2016

29. Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Author

McGranahan, N., Rosenthal, R., Hiley, C.T., Rowan, A.J., Watkins, T.B.K., Wilson, G.A., Birkbak, N.J., Veeriah, S., Van Loo, P., Herrero, J., Swanton, C., Jamal-Hanjani, M., Shafi, S., Czyzewska-Khan, J., Johnson, D., Laycock, J., Bosshard-Carter, L., Gorman, P., Hynds, R.E., Wilson, G., Horswell, S., Mitter, R., Escudero, M., Stewart, A., Rowan, A., Xu, H., Turajlic, S., Hiley, C., Abbosh, C., Goldman, J., Stone, R.K., Denner, T., Matthews, N., Elgar, G., Ward, S., Costa, M., Begum, S., Phillimore, B., Chambers, T., Nye, E., Graca, S., Al Bakir, M., Joshi, K., Furness, A., Ben Aissa, A., Wong, Y.N.S., Georgiou, A., Quezada, S., Hartley, J.A., Lowe, H.L., Lawrence, D., Hayward, M., Panagiotopoulos, N., Kolvekar, S., Falzon, M., Borg, E., Marafioti, T., Simeon, C., Hector, G., Smith, A., Aranda, M., Novelli, M., Oukrif, D., Janes, S.M., Thakrar, R., Forster, M., Ahmad, T., Lee, S.M., Papadatos-Pastos, D., Carnell, D., Mendes, R., George, J., Navani, N., Ahmed, A., Taylor, M., Choudhary, J., Summers, Y., Califano, R., Taylor, P., Shah, R., Krysiak, P., Rammohan, K., Fontaine, E., Booton, R., Evison, M., Crosbie, P., Moss, S., and the TRACERx Consortium, .

Abstract

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer.

Published
2017

30. Phylogenetic ctDNA analysis depicts early stage lung cancer evolution

Author

Abbosh, C, Birkbak, NJ, Wilson, GA, Jamal-Hanjani, M, Constantin, T, Salari, R, Quesne, JL, Moore, DA, Veeriah, S, Rosenthal, R, Marafioti, T, Kirkizlar, E, Watkins, TBK, McGranahan, N, Ward, S, Martinson, L, Riley, J, Fraioli, F, Bakir, MA, GrÖnroos, E, Zambrana, F, Endozo, R, Bi, WL, Fennessy, FM, Sponer, N, Johnson, D, Laycock, J, Shafi, S, Czyzewska-Khan, J, Rowan, A, Chambers, T, Matthews, N, Turajlic, S, Hiley, C, Lee, SM, Forster, MD, Ahmad, T, Falzon, M, Borg, E, Lawrence, D, Hayward, M, Kolvekar, S, Panagiotopoulos, N, Janes, SM, Thakrar, R, Ahmed, A, Blackhall, F, Summers, Y, Hafez, D, Naik, A, Ganguly, A, Kareht, S, Shah, R, Joseph, L, Quinn, AM, Crosbie, P, Naidu, B, Middleton, G, Langman, G, Trotter, S, Nicolson, M, Remmen, H, Kerr, K, Chetty, M, Gomersall, L, Fennell, DA, Nakas, A, Rathinam, S, Anand, G, Khan, S, Russell, P, Ezhil, V, Ismail, B, Irvin-sellers, M, Prakash, V, Lester, JF, Kornaszewska, M, Attanoos, R, Adams, H, Davies, H, Oukrif, D, Akarca, AU, Hartley, JA, Lowe, HL, Lock, S, Iles, N, Bell, H, Ngai, Y, Elgar, G, Szallasi, Z, Schwarz, RF, Herrero, J, Stewart, A, Quezada, SA, Van Loo, P, Dive, C, Lin, CJ, Rabinowitz, M, Aerts, HJWL, Hackshaw, A, Shaw, JA, Zimmermann, BG, Swanton, C, Bosshard-Carter, L, Goh, G, Gorman, P, Murugaesu, N, Hynds, RE, Wilson, G, Horswell, S, Al Bakir, M, Mitter, R, Escudero, M, Xu, H, Goldman, J, Stone, RK, Denner, T, Biggs, J, Costa, M, Begum, S, Phillimore, B, Nye, E, Graca, S, Joshi, K, Furness, A, Aissa, AB, Wong, YNS, Georgiou, A, Quezada, S, Simeon, C, Hector, G, Smith, A, Aranda, M, Novelli, M, Forster, M, Papadatos-Pastos, D, Carnell, D, Mendes, R, George, J, Navani, N, Taylor, M, Choudhary, J, Califano, R, Taylor, P, Krysiak, P, Rammohan, K, Fontaine, E, Booton, R, Evison, M, Moss, S, Idries, F, Bishop, P, Chaturved, A, Marie Quinn, A, Doran, H, leek, A, Harrison, P, Moore, K, Waddington, R, Novasio, J, Rogan, J, Smith, E, Tugwood, J, Brady, G, Rothwell, DG, Chemi, F, Pierce, J, Gulati, S, Bellamy, M, Bancroft, H, Kerr, A, Kadiri, S, Webb, J, Djearaman, M, Fennell, D, Le Quesne, J, Moore, D, Thomas, A, Walter, H, Monteiro, W, Marshall, H, Nelson, L, Bennett, J, Primrose, L, Amadi, A, Palmer, S, Miller, J, Buchan, K, Lester, J, Edwards, A, Morgan, F, Verjee, A, MacKenzie, M, Wilcox, M, Smith, S, Gower, N, Ottensmeier, C, Chee, S, Johnson, B, Alzetani, A, Shaw, E, Lim, E, De Sousa, P, Tavares Barbosa, M, Bowman, A, Jordan, S, Rice, A, Raubenheimer, H, Proli, C, Elena Cufari, M, Ronquillo, JC, Kwayie, A, Bhayani, H, Hamilton, M, Bakar, Y, Mensah, N, Ambrose, L, Devaraj, A, Buderi, S, Finch, J, Azcarate, L, Chavan, H, Green, S, Mashinga, H, Nicholson, AG, Lau, K, Sheaff, M, Schmid, P, Conibear, J, Light, T, Horey, T, Danson, S, Bury, J, Edwards, J, Hill, J, Matthews, S, Kitsanta, Y, Suvarna, K, Fisher, P, Keerio, AD, Shackcloth, M, Gosney, J, Postmus, P, Feeney, S, Asante-Siaw, J, Constatin, T, Zimmermann, B, Dentro, S, Dessimoz, C, Shiu, K-K, Bridgewater, J, Hochauser, D, Beck, S, Parker, P, Walczak, H, Enver, T, Proctor, I, Sinclair, R, Lok, C-W, Mitchison, M, Trevisan, G, Lynch, M, Brandner, S, Gishen, F, Tookman, A, Stone, P, Sterling, C, Larkin, J, Attard, G, Eeles, R, Foster, C, Bova, S, Sottoriva, A, Chowdhury, S, Ashish, C, Spicer, J, Stares, M, Lynch, J, Caldas, C, Brenton, J, Fitzgerald, R, Jimenez-Linan, M, Provenzano, E, Cluroe, A, Stewart, G, Watts, C, Gilbertson, R, McDermott, U, Tavare, S, Maughan, T, Tomlinson, I, Campbell, P, McNeish, I, Biankin, A, Chambers, A, Fraser, S, Oien, K, Krebs, M, Marais, R, Carter, L, Nonaka, D, Dhomen, N, Shaw, J, Baijal, S, Tanchel, B, Collard, M, Cockcroft, P, Taylor, J, Colloby, P, Olisemeke, B, Wilson, R, Harrison, D, Loda, M, Flanagan, A, McKenzie, M, Lederman, J, Sharp, A, and Farrelly, L

Subjects
0301 basic medicine, Oncology, Lung Neoplasms, IMPACT, Biopsy, DNA Mutational Analysis, Drug resistance, Metastasis, 0302 clinical medicine, Limit of Detection, Carcinoma, Non-Small-Cell Lung, Medicine, Neoplasm Metastasis, Early Detection of Cancer, Multidisciplinary, medicine.diagnostic_test, Phylogenetic tree, DNA, Neoplasm, STATISTICS, 3. Good health, Tumor Burden, Multidisciplinary Sciences, Cell Tracking, PEACE consortium, 030220 oncology & carcinogenesis, Disease Progression, Science & Technology - Other Topics, medicine.medical_specialty, CARCINOMA, Tumour heterogeneity, General Science & Technology, Early detection, Evolution, Molecular, 03 medical and health sciences, Internal medicine, MD Multidisciplinary, Carcinoma, Humans, Cell Lineage, Lung cancer, Postoperative Care, Science & Technology, MUTATIONS, TRACERx consortium, business.industry, CIRCULATING TUMOR DNA, Reproducibility of Results, medicine.disease, R1, NEGATIVE BREAST-CANCER, Clone Cells, 030104 developmental biology, Drug Resistance, Neoplasm, UPTAKE RATIO, Immunology, FDG PET, Neoplasm Recurrence, Local, business, Multiplex Polymerase Chain Reaction
Abstract

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies.

Published
2017

31. Randomized Phase III Trial of Erlotinib versus Docetaxel in Patients with Advanced Squamous Cell Non–Small Cell Lung Cancer Failing First-Line Platinum-Based Doublet Chemotherapy Stratified by VeriStrat Good versus VeriStrat Poor. The European Thoracic Oncology Platform (ETOP) EMPHASIS-lung Trial

Author

Peters, S. Stahel, R.A. Dafni, U. Ponce Aix, S. Massutí, B. Gautschi, O. Coate, L. López Martín, A. van Heemst, R. Berghmans, T. Meldgaard, P. Cobo Dols, M. Garde Noguera, J. Curioni-Fontecedro, A. Rauch, D. Mark, M.T. Cuffe, S. Biesma, B. van Henten, A.M.J. Juan Vidal, Ó. Palmero Sanchez, R. Villa Guzmán, J.C. Collado Martin, R. Peralta, S. Insa, A. Summers, Y. Láng, I. Horgan, A. Ciardiello, F. de Hosson, S. Pieterman, R. Groen, H.J.M. van den Berg, P.M. Zielinski, C.C. Chittazhathu Kurian Kuruvilla, Y. Gasca-Ruchti, A. Kassapian, M. Novello, S. Torri, V. Tsourti, Z. Gregorc, V. Smit, E.F. EMPHASIS-lung Collaborative Group

Subjects
neoplasms, respiratory tract diseases
Abstract

Introduction Docetaxel and erlotinib are registered second-line treatments for wild-type EGFR NSCLC. Previous studies suggested a predictive value of the VeriStrat test in second-line therapy of NSCLC, classifying patients as either VeriStrat good or VeriStrat poor. EMPHASIS-lung aimed at exploring this predictive effect in patients with squamous cell NSCLC. The trial closed prematurely because of low accrual and results from other trials. Our analysis includes an exploratory combined analysis with results from the PROSE trial. Methods EMPHASIS-lung was a randomized phase III multicenter trial exploring the differential effect of second-line erlotinib versus docetaxel on progression-free survival (PFS) in VeriStrat good versus VeriStrat poor patients with squamous cell NSCLC. Results A total of 80 patients were randomized, with 72.5% categorized as VeriStrat good. Patient characteristics were balanced between VeriStrat status and treatment groups. The median PFS times with docetaxel and erlotinib treatment in the VeriStrat good cohort were 4.1 and 1.6 months, respectively, versus 1.9 and 2.1 months, respectively, in the VeriStrat poor cohort. The median overall survival (OS) times with docetaxel and erlotinib treatment in the VeriStrat good cohort were 7.8 and 8.4 months, respectively, and 4.4 and 5.2 months, respectively, in the VeriStrat poor cohort. An additional exploratory analysis was performed; in it, 47 patients from the squamous cell subgroup of PROSE were included in a combined analysis, contributing with 45 PFS and 41 OS events. Conclusions The final analysis of EMPHASIS-lung did not show a differential effect on PFS for erlotinib versus docetaxel stratified by VeriStrat status. Similarly, in the combined analysis, no significant treatment by VeriStrat status interaction was observed (interaction p = 0.24 for PFS and 0.45 for OS, stratified by study). © 2017 International Association for the Study of Lung Cancer

Published
2017

32. Amisulpride prevents nausea and vomiting associated with highly emetogenic chemotherapy: a randomised, double-blind, placebo-controlled, dose-ranging trial

Author

Herrstedt, J., primary, Summers, Y., additional, Jordan, K., additional, von Pawel, J., additional, Jakobsen, A. H., additional, Ewertz, M., additional, Chan, S., additional, Naik, J. D., additional, Karthaus, M., additional, Dubey, S., additional, Davis, R., additional, and Fox, G. M., additional

Published
2018
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34. Pembrolizumab in performance status 2 patients with non-small cell lung cancer (NSCLC): Results of the PePS2 trial

Author

Middleton, G., primary, Brock, K., additional, Summers, Y., additional, Connibear, J., additional, Shah, R., additional, Ottensmeier, C., additional, Shaw, P., additional, Ming-Lee, S., additional, Popat, S., additional, Barrie, C., additional, Barone, G., additional, Mant, R., additional, Savage, J.S., additional, and Billingham, L., additional

Published
2018
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35. P1.01-26 Single-Centre Experience of Clinical Outcomes for Advanced Lung Cancer Patients in Phase I Clinical Trials

Author

Graham, D., primary, Jordan, T., additional, Tinsley, N., additional, Aruketty, S., additional, Vickers, A., additional, Kelly, C., additional, Kurup, R., additional, White, A., additional, Smith, A., additional, Walsh, A., additional, Thomson, C., additional, O'Reilly, S., additional, Norfolk, M., additional, Chang, D., additional, Blackhall, F., additional, Summers, Y., additional, Califano, R., additional, Taylor, P., additional, Thistlethwaite, F., additional, Cook, N., additional, Carter, L., additional, and Krebs, M., additional

Published
2018
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37. P2.13-01 Brigatinib Use in England – Where Next?

Author

Gomes, F., primary, Yip, K., additional, Blackhall, F., additional, Greystoke, A., additional, Califano, R., additional, Ghosh, S., additional, Newsom-Davis, T., additional, Mills, H., additional, Ahmed, S., additional, Harle, A., additional, and Summers, Y., additional

Published
2018
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39. Single institution analysis of pneumocystis jirovecii pneumonia in patients undergoing treatment for lung cancer: recommendations for PJP prophylaxis

Author

Croxford, W., primary, Haslett, K., additional, Syed, J., additional, Bayman, N., additional, Blackhall, F., additional, Califano, R., additional, Chan, C., additional, Coote, J., additional, Cove-Smith, L., additional, Harris, M., additional, Hughes, S., additional, Faivre-Finn, C., additional, Marti-Marti, F., additional, Pemberton, L., additional, Summers, Y., additional, Taylor, P., additional, Woolf, D., additional, and Sheikh, H., additional

Published
2018
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40. Retrospective analysis of outcomes in UK patients with advanced NSCLC and ROS1 rearrangement

Author

Tokaca, N., primary, Pouptsis, A., additional, Karapanagiotou, E., additional, Spicer, J., additional, Halkyard, E., additional, Blackhall, F., additional, Summers, Y., additional, Greystoke, A., additional, Bhosle, J., additional, Jones, A., additional, Newsom-Davis, T., additional, Nicolson, M., additional, O’Brien, M., additional, Yousaf, N., additional, and Popat, S., additional

Published
2018
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41. Treatment pathways in small cell lung cancer (SCLC) in the Greater Manchester (GM) network- an analysis of timeliness of therapy and impact on survival

Author

Sheikh, H., primary, Yates, J., additional, Blackhall, F., additional, Bayman, N., additional, Coote, J., additional, Califano, R., additional, Chan, C., additional, Harris, M., additional, Hughes, S., additional, Faivre-Finn, C., additional, Marti-Marti, F., additional, Taylor, P., additional, Summers, Y., additional, Pemberton, L., additional, Woolf, D., additional, and Zhou, C., additional

Published
2018
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43. Intracranial efficacy of brigatinib (BRG) in patients (Pts) With crizotinib (CRZ)-refractory anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) and baseline CNS metastases

Author

Ou, S.-H.I., primary, Tiseo, M., additional, Camidge, R., additional, Ahn, M.-J., additional, Huber, R.M., additional, Hochmair, M.J., additional, Kim, S.-W., additional, West, H.L., additional, Reckamp, K.L., additional, Molina, J.R., additional, Liu, G., additional, Delmonte, A., additional, Viteri, S., additional, Bearz, A., additional, Summers, Y., additional, Reichmann, W., additional, Kerstein, D., additional, Gettinger, S.N., additional, and Kim, D.-W., additional

Published
2017
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48. Amisulpride prevents nausea and vomiting associated with highly emetogenic chemotherapy: a randomised, double-blind, placebo-controlled, dose-ranging trial.

Author

Ewertz, M., Herrstedt, J., Karthaus, M., Dubey, S., Davis, R., Fox, G. M., Summers, Y., Jordan, K., von Pawel, J., Jakobsen, A. H., Chan, S., and Naik, J. D.

Subjects
AMISULPRIDE, NAUSEA, DOPAMINE antagonists, VOMITING, CANCER chemotherapy
Abstract

Purpose: Chemotherapy-induced nausea and vomiting (CINV) remain significant clinical problems, especially in the delayed phase (24-120 h after chemotherapy). Amisulpride is a dopamine D2/D3-receptor antagonist previously shown to be an effective intravenous antiemetic. We conducted a randomised, double-blind study to characterise the dose response of oral amisulpride in delayed phase CINV.Methods: Chemotherapy-naïve patients receiving cisplatin ≥ 70 mg/m2 or an anthracycline-cyclophosphamide regimen for breast cancer received, on day 1, 20 mg amisulpride and 8-16 mg ondansetron intravenously followed, once daily on days 2-4, by 10, 20 or 40 mg oral amisulpride or placebo. A control group receiving standard three-drug prophylaxis was enrolled for assay sensitivity purposes. The primary endpoint was complete response (CR), defined as no emesis or rescue medication use, in the delayed phase.Results: Three hundred eighteen subjects were evaluable per protocol. CR rate (24-120 h) was 20% with placebo and 46% with 10 mg amisulpride (p = 0.006 after multiplicity adjustment); in the three-drug control group, it was 59%. Emesis, nausea and 0-120-h CR rate were significantly improved with 10 mg amisulpride compared to placebo. Higher doses of amisulpride were not more effective than 10 mg. In patients with acute phase CR, delayed phase CR rate was 44% for placebo, 75% for 10 mg amisulpride (p = 0.022) and 70% for the 3-drug control. No significant differences were seen between groups in safety parameters.Conclusions: Amisulpride 10 mg orally is safe and superior to placebo at preventing delayed CINV caused by highly emetogenic chemotherapy.Trial Registration: NCT01857232. [ABSTRACT FROM AUTHOR]

Published
2019
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