Search

Your search keyword '"L. Paz-Ares"' showing total 560 results
Start Over Author "L. Paz-Ares"
560 results on '"L. Paz-Ares"'

1. A potential therapeutic strategy based on acute oxidative stress induction for wild-type NRF2/KEAP1 lung squamous cell carcinoma

Author

M. Sánchez-Ortega, A. Garrido, C. Cirauqui, L. Sanz-Gonzalez, M.C. Hernández, A. González-García, K. Obregon, I. Ferrer, L. Paz-Ares, and A.C. Carrera

Subjects
LUSC treatment, Transient ROS inducers, SETD5, MicroRNA126, PI3K, p85βPI3K, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Extensive efforts have been conducted in the search for new targetable drivers of lung squamous cell carcinoma (LUSC); to date, however, candidates remain mostly unsuccessful. One of the oncogenic pathways frequently found to be active in LUSC is NFE2L2 (NRF2 transcription factor), the levels of which are regulated by KEAP1. Mutations in NFE2L2 or KEAP1 trigger NRF2 activation, an essential protector against reactive oxygen species (ROS). We hypothesized that the frequency of NRF2 activation in LUSC (∼35 %) may reflect a sensitivity of LUSC to ROS. Results from this study reveal that whereas tumors containing active forms of NRF2 were protected, ROS induction in wild-type NFE2L2/KEAP1 LUSC cells triggered ferroptosis. The mechanism of ROS action in normal-NRF2 LUSC cells involved transient NRF2 activation, miR-126-3p/miR-126-5p upregulation, and reduction of p85β and SETD5 levels. SETD5 levels reduction triggered pentose pathway gene levels increase to toxic values. Simultaneous depletion of p85βPI3K and SETD5 triggered LUSC cell death, while p85βPI3K and SETD5 overexpression rescued survival of ROS-treated normal-NRF2 LUSC cells. This shows that the cascade involving NRF2 > miR-126-3p, miR-126-5p > p85βPI3K and SETD5 is responsible for ROS-induced cell death in normal-NRF2 LUSC. Transient ROS-induced cell death is shown in 3D spheroids, patient-derived organoids, and in xenografts of wild-type NFE2L2/KEAP1 LUSC cells, supporting the potential of acute local ROS induction as a therapeutic strategy for LUSC patients with normal-NRF2.

Published
2024
Full Text
View/download PDF

3. Results of screening in early and advanced thoracic malignancies in the EORTC pan-European SPECTAlung platform

Author

M. Morfouace, S. Novello, A. Stevovic, C. Dooms, U. Janžič, T. Berghmans, R. Dziadziuszko, T. Gorlia, E. Felip, L. Paz-Ares, J. Mazieres, M. O’Brien, P. Bironzo, J. Vansteenkiste, L. Lacroix, A. C. Dingemans, V. Golfinopoulos, and B. Besse

Subjects
Medicine, Science
Abstract

Abstract Access to a comprehensive molecular alteration screening is patchy in Europe and quality of the molecular analysis varies. SPECTAlung was created in 2015 as a pan-European screening platform for patients with thoracic malignancies. Here we report the results of almost 4 years of prospective molecular screening of patients with thoracic malignancies, in terms of quality of the program and molecular alterations identified. Patients with thoracic malignancies at any stage of disease were recruited in SPECTAlung, from June 2015 to May 2019, in 7 different countries. Molecular tumour boards were organised monthly to discuss patients’ molecular and clinical profile and possible biomarker-driven treatments, including clinical trial options. FFPE material was collected and analysed for 576 patients with diagnosis of pleural, lung, or thymic malignancies. Ultimately, 539 patients were eligible (93.6%) and 528 patients were assessable (91.7%). The turn-around time for report generation and molecular tumour board was 214 days (median). Targetable molecular alterations were observed in almost 20% of cases, but treatment adaptation was low (3% of patients). SPECTAlung showed the feasibility of a pan-European screening platform. One fifth of the patients had a targetable molecular alteration. Some operational issues were discovered and adapted to improve efficiency.

Published
2022
Full Text
View/download PDF

4. Safety and efficacy of pralsetinib in RET fusion–positive non-small-cell lung cancer including as first-line therapy

Author

F. Griesinger, G. Curigliano, M. Thomas, V. Subbiah, C.S. Baik, D.S.W. Tan, D.H. Lee, D. Misch, E. Garralda, D.-W. Kim, A.J. van der Wekken, J.F. Gainor, L. Paz-Ares, S.V. Liu, G.P. Kalemkerian, Y. Houvras, D.W. Bowles, A.S. Mansfield, J.J. Lin, V. Smoljanovic, A. Rahman, S. Kong, A. Zalutskaya, M. Louie-Gao, A.L. Boral, J. Mazières, Institut Català de la Salut, [Griesinger F] Department of Hematology and Oncology, Pius-Hospital, University of Oldenburg, Oldenburg, Germany. [Curigliano G] European Institute of Oncology, IRCCS, Milan, Italy. Department of Oncology and Hemato-Oncology, University of Milano, Milan, Italy. [Thomas M] Department of Thoracic Oncology, Thoraxklinik, University Heidelberg and Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany. [Subbiah V] Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, USA. [Baik CS] Division of Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, USA. [Tan DSW] Division of Medical Oncology, National Cancer Centre Singapore, Singapore. [Garralda E] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Otros calificadores::/uso terapéutico [Otros calificadores], Medicaments antineoplàstics - Ús terapèutic, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS], diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Hematology, Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Carcinoma, Non-Small-Cell Lung [DISEASES], neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas [ENFERMEDADES], Other subheadings::Other subheadings::/drug therapy [Other subheadings], Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], targeted therapy, Oncology, non-small-cell lung cancer, pralsetinib, Avaluació de resultats (Assistència sanitària), Other subheadings::/therapeutic use [Other subheadings], Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS], Pulmons - Càncer - Tractament, frontline therapy, RET fusion, RET inhibition
Abstract

RET inhibition; Pralsetinib; Targeted therapy Inhibición de RET; Pralsetinib; Terapia dirigida Inhibició de RET; Pralsetinib; Teràpia dirigida Background RET fusions are present in 1%-2% of non-small-cell lung cancer (NSCLC). Pralsetinib, a highly potent, oral, central nervous system-penetrant, selective RET inhibitor, previously demonstrated clinical activity in patients with RET fusion–positive NSCLC in the phase I/II ARROW study, including among treatment-naive patients. We report an updated analysis from the ARROW study. Patients and methods ARROW is a multi-cohort, open-label, phase I/II study. Eligible patients were ≥18 years of age with locally advanced or metastatic solid tumours and an Eastern Cooperative Oncology Group performance status of 0-2 (later 0-1). Patients initiated pralsetinib at the recommended phase II dose of 400 mg once daily until disease progression, intolerance, consent withdrawal, or investigator’s decision. The co-primary endpoints (phase II) were overall response rate (ORR) by blinded independent central review and safety. Results Between 17 March 2017 and 6 November 2020 (data cut-off), 281 patients with RET fusion–positive NSCLC were enrolled. The ORR was 72% [54/75; 95% confidence interval (CI) 60% to 82%] for treatment-naive patients and 59% (80/136; 95% CI 50% to 67%) for patients with prior platinum-based chemotherapy (enrolment cut-off for efficacy analysis: 22 May 2020); median duration of response was not reached for treatment-naive patients and 22.3 months for prior platinum-based chemotherapy patients. Tumour shrinkage was observed in all treatment-naive patients and in 97% of patients with prior platinum-based chemotherapy; median progression-free survival was 13.0 and 16.5 months, respectively. In patients with measurable intracranial metastases, the intracranial response rate was 70% (7/10; 95% CI 35% to 93%); all had received prior systemic treatment. In treatment-naive patients with RET fusion–positive NSCLC who initiated pralsetinib by the data cut-off (n = 116), the most common grade 3-4 treatment-related adverse events (TRAEs) were neutropenia (18%), hypertension (10%), increased blood creatine phosphokinase (9%), and lymphopenia (9%). Overall, 7% (20/281) discontinued due to TRAEs. Conclusions Pralsetinib treatment produced robust efficacy and was generally well tolerated in treatment-naive patients with advanced RET fusion–positive NSCLC. Results from the confirmatory phase III AcceleRET Lung study (NCT04222972) of pralsetinib versus standard of care in the first-line setting are pending. This work was supported by Blueprint Medicines Corporation and F. Hoffmann-La Roche, Ltd, Switzerland (no grant number).

Published
2022
Full Text
View/download PDF

5. 75TiP A multicenter, open-label, phase II trial evaluating the safety and efficacy of folate receptor alpha (FRα) antibody-drug conjugate (ADC) farletuzumab ecteribulin (FZEC*) in patients with previously treated, metastatic non-small cell lung cancer (NSCLC) adenocarcinoma (AC)

Author

D. Planchard, L. Paz-Ares, A. Spira, E. Felip, S. McCune, T. Cascella, J. Dennie, P. Bhagavatheeswaran, C. Dumitru, and H. Borghaei

Subjects
Pulmonary and Respiratory Medicine, Oncology
Published
2023
Full Text
View/download PDF

7. 41P Efficacy of first-line (1L) nivolumab (N) + ipilimumab (I) by tumor histologic subtype in patients (pts) with metastatic nonsquamous NSCLC (mNSQ-NSCLC)

Author

H. Borghaei, D. Balli, L. Paz-Ares, M. Reck, S.S. Ramalingam, J.R. Brahmer, T-E. Ciuleanu, A. Pluzanski, J-S. Lee, J. Gainor, M. Schenker, A. Schoenfeld, R. Bernabe Caro, N. Ready, K.H. Lee, B. Zurawski, C. Audigier-Valette, V. Baxi, W. Geese, and K.J. O’Byrne

Subjects
Pulmonary and Respiratory Medicine, Oncology
Published
2023
Full Text
View/download PDF

9. Isatuximab plus atezolizumab in patients with advanced solid tumors: results from a phase I/II, open-label, multicenter study

Author

M. Simonelli, E. Garralda, F. Eskens, M. Gil-Martin, C.-J. Yen, R. Obermannova, Y. Chao, S. Lonardi, B. Melichar, V. Moreno, M.-L. Yu, A. Bongiovanni, E. Calvo, S. Rottey, J.-P. Machiels, A. Gonzalez-Martin, L. Paz-Ares, C.-L. Chang, W. Mason, C.-C. Lin, D.A. Reardon, M. Vieito, A. Santoro, R. Meng, G. Abbadessa, F. Menas, H. Lee, Q. Liu, C. Combeau, N. Ternes, S. Ziti-Ljajic, C. Massard, Medical Oncology, Institut Català de la Salut, [Simonelli M] IRCCS Humanitas Research Hospital, Rozzano, Italy. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy. [Garralda E] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Eskens F] Erasmus MC Cancer Institute, Rotterdam, the Netherlands. [Gil-Martin M] Institut Català d’Oncologia-IDIBELL, L’Hospitalet, Barcelona, Spain. [Yen CJ] National Cheng Kung University, Tainan, Taiwan. [Santoro A] Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, and UCL - (SLuc) Service d'oncologie médicale

Subjects
atezolizumab, Cancer Research, anti-PD-L1, Carcinoma, Hepatocellular, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Other subheadings::Other subheadings::/drug therapy [Other subheadings], Quimioteràpia combinada, B7-H1 Antigen, neoplasias [ENFERMEDADES], Càncer de fetge, SDG 3 - Good Health and Well-being, anti-CD38, Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Medicine and Health Sciences, Tumor Microenvironment, Humans, Tumors, Càncer - Tractament, Cell Physiological Phenomena::Cellular Microenvironment::Tumor Microenvironment [PHENOMENA AND PROCESSES], fenómenos fisiológicos celulares::microambiente celular::microambiente tumoral [FENÓMENOS Y PROCESOS], Liver Neoplasms, terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Forkhead Transcription Factors, solid tumors, Neoplasms [DISEASES], Oncology, Liver cancer, isatuximab
Abstract

Atezolizumab; Isatuximab; Solid tumors Atezolizumab; Isatuximab; Tumores sólidos Atezolizumab; Isatuximab; Tumors sòlids Background The anti-CD38 antibody isatuximab is approved for the treatment of relapsed/refractory multiple myeloma, but there are no data on its efficacy in solid tumors. This phase I/II study (NCT03637764) assessed the safety and activity of isatuximab plus atezolizumab (Isa + Atezo), an anti-programmed death-ligand 1 (PD-L1) antibody, in patients with immunotherapy-naive solid tumors: epithelial ovarian cancer (EOC), glioblastoma (GBM), hepatocellular carcinoma (HCC), and squamous cell carcinoma of the head and neck (SCCHN). Patients and methods Phase I assessed safety, tolerability, pharmacokinetics, pharmacodynamics, and the recommended phase II dose (RP2D) of isatuximab 10 mg/kg intravenously (i.v.) every week for 3 weeks followed by once every 3 weeks + atezolizumab 1200 mg i.v. every 3 weeks. Phase II used a Simon’s two-stage design to assess the overall response rate or progression-free survival rate at 6 months (GBM cohort). Interim analysis was carried out at 6 months following first dose of the last enrolled patient in each cohort. Pharmacodynamic biomarkers were tested for CD38, PD-L1, tumor-infiltrating immune cells, and FOXP3+ regulatory T cells (Tregs) in the tumor microenvironment (TME). Results Overall, 107 patients were treated (EOC, n = 18; GBM, n = 33; HCC, n = 27; SCCHN, n = 29). In phase I, Isa + Atezo showed an acceptable safety profile, no dose-limiting toxicities were observed, and RP2D was confirmed. Most patients experienced ≥1 treatment-emergent adverse event (TEAE), with ≤48.5% being grade ≥3. The most frequent TEAE was infusion reactions. The study did not continue to stage 2 based on prespecified targets. Tumor-infiltrating CD38+ immune cells were reduced and almost cleared after treatment. Isa + Atezo did not significantly modulate Tregs or PD-L1 expression in the TME. Conclusions Isa + Atezo had acceptable safety and tolerability. Clinical pharmacodynamic evaluation revealed efficient target engagement of isatuximab via treatment-mediated reduction of CD38+ immune cells in the TME. Based on clinical data, CD38 inhibition does not improve responsiveness to PD-L1 blockade in these patients. This work was sponsored by Sanofi (no grant number).

Published
2022

10. VP3-2022: Pembrolizumab (pembro) versus placebo for early-stage non-small cell lung cancer (NSCLC) following complete resection and adjuvant chemotherapy (chemo) when indicated: Randomized, triple-blind, phase III EORTC-1416-LCG/ETOP 8-15 – PEARLS/KEYNOTE-091 study

Author

L. Paz-Ares, M.E.R. O'Brien, M. Mauer, U. Dafni, K. Oselin, L. Havel, E. Esteban Gonzalez, D. Isla, A. Martinez-Marti, M. Faehling, M. Tsuboi, J-S. Lee, K. Nakagawa, J. Yang, S.M. Keller, N. Jha, S.I. Marreaud, R.A. Stahel, S. Peters, and B. Besse

Subjects
Oncology, Hematology
Published
2022
Full Text
View/download PDF

11. Actualisation des données de phase I de recherche de dose et premières données de la phase d’expansion du tarlatamab, un anticorps bispécifique ciblant la protéine DLL3 et engageant les lymphocytes T, dans le cancer bronchique à petites cellules (CBPC)

Author

S. Champiat, H. Izumi, M. Johnson, H. Borghaei, T. Owonikoko, V. Lai, M. Boyer, H.D. Hummel, R. Govindan, N. Steeghs, F. Blackhall, N. Reguart, A. Dowlati, K. Ouali, Y. Zhang, A. Goldrick, S. Mukherjee, and L. Paz-Ares

Subjects
Pulmonary and Respiratory Medicine
Published
2023
Full Text
View/download PDF

13. 165P SCLC subtypes are associated with distinct dinicopathological features and outcomes: A biomarker analysis from the CANTABRICO study

Author

P. Rocha, I. Sanchez, L. Masfarre Pinto, M. Giner, N. Navarro Gorro, A. Rios Hoyo, A. Taus Garcia, S. Pérez-Buira, É. Torres-Fernandez, S. Clave, B. Bellosillo Paricio, F. Rojo, L. Paz-Ares, C. Martí Cubells, C. Aguado de la Rosa, M.D. Isla Casado, R. Garcia-Campelo, L. Baez, Á. Callejo Mellén, and E. Arriola

Subjects
Pulmonary and Respiratory Medicine, Oncology
Published
2023
Full Text
View/download PDF

14. 1010P Assessment of early resistance mechanisms to first-line osimertinib in EGFR-mutant NSCLC using spatial transcriptomics

Author

G. Ruiz de Garibay, B. Roch, P. Garrido Lopez, D. Isla, C. Aguado, A. Callejo Perez, R. Marse Fabregat, M.R. Garcia Campelo, A. Blasco Cordellat, J.M. Sanchez Torres, R. Bernabe Caro, O.J. Juan Vidal, J. De Castro Carpeno, F.F. Franco, I. Ramos Garcia, A. Gomez Rueda, E. Conde Gallego, S. Ponce Aix, L. Paz-Ares, and J. Zugazagoitia

Subjects
Oncology, Hematology
Published
2022
Full Text
View/download PDF

17. EP08.01-029 NIVIPI-BRAIN, A Phase II Study of Nivolumab plus Ipilimumab Combined with Chemotherapy for Patients with NSCLC and Synchronous Brain Metastases

Author

E. Nadal, A. Cantero, A.L. Ortega, M. Dómine, A. Barba, A. Blasco, J. García, J. Mosquera, S. Vázquez, D. Rodríguez, R. López-Castro, O. Juan-Vidal, A. Sánchez, L. Paz-Ares, A. Hernández, P. Iranzo, P. Diz, M. Provencio, M. Simó, V. Navarro, and J. Bruna

Subjects
Pulmonary and Respiratory Medicine, Oncology
Published
2022
Full Text
View/download PDF

18. OA03.04 Phase I A Study to Evaluate GDC-6036 Monotherapy in Patients with Non-small Cell Lung Cancer (NSCLC) with KRAS G12C Mutation

Author

A. Sacher, M.R. Patel, W.H. Miller, J. Desai, E. Garralda, S. Bowyer, T.W. Kim, M. De Miguel, A. Falcon, M.G. Krebs, J. Lee, M. Cheng, S.-W. Han, E. Shacham-Shmueli, M. Forster, G. Jerusalem, E. Massarelli, L. Paz-Ares Rodriguez, H. Prenen, I. Walpole, K. Arbour, Y. Choi, N.V. Dharia, M. Lin, S. Mandlekar, S. Royer Joo, Z. Shi, J. Schutzman, and P. LoRusso

Subjects
Pulmonary and Respiratory Medicine, Oncology
Published
2022
Full Text
View/download PDF

24. P2.07-02 RET Fusion Testing with FISH and Real-Time PCR: a Comparison with RNA-Based Next-Generation Sequencing in RET Positive NSCLC

Author

S. Hernandez, J.L. Rodriguez Carrillo, A. Caminoa, A. Benito, R. Martinez, M. Alonso, S. Clave, E. Arriola, I. Esteban-Rodriguez, J. De Castro, I. Sansano, E. Felip, I. Abdulkader, J. Garcia, F. Rojo, M. Domine, C. Teixido, N. Reguart, D. Compañ, A. Insa, N. Mancheño, S. Palanca, O. Juan, N. Baixeras, E. Nadal, M. Cebollero, A. Calles, P. Martin, C. Salas, M. Provencio, I. Aranda, B. Massuti, L. Lopez-Vilaro, M. Majem, P. Garrido, L. Paz-Ares, F. Lopez-Rios, and E. Conde

Subjects
Pulmonary and Respiratory Medicine, Oncology
Published
2022
Full Text
View/download PDF

26. 1532P Phase IIIb study of durvalumab plus platinum-etoposide in first-line treatment of extensive-stage small cell lung cancer (CANTABRICO): Preliminary efficacy results

Author

D. Isla, E. Arriola, M.R. Garcia Campelo, P. Diz Tain, C. Marti Blanco, M.M. Lopez-Brea Piqueras, A.L. Moreno Vega, L.A. Leon Mateos, J.M. Oramas Rodriguez, V. Gutierrez Calderon, M. Majem Tarruella, A. Sanchez Hernandez, C. Aguado de la Rosa, R. Alvarez Cabellos, J.L. Marti Ciriquian, A. Moreno Paul, J.L. Firvida Perez, Á. Callejo Mellén, L. Baez, and L. Paz-Ares

Subjects
Oncology, Hematology
Published
2022
Full Text
View/download PDF

31. ESMO expert consensus statements on the management of EGFR mutant non-small-cell lung cancer

Author

A. Passaro, N. Leighl, F. Blackhall, S. Popat, K. Kerr, M.J. Ahn, M.E. Arcila, O. Arrieta, D. Planchard, F. de Marinis, A.M. Dingemans, R. Dziadziuszko, C. Faivre-Finn, J. Feldman, E. Felip, G. Curigliano, R. Herbst, P.A. Jänne, T. John, T. Mitsudomi, T. Mok, N. Normanno, L. Paz-Ares, S. Ramalingam, L. Sequist, J. Vansteenkiste, I.I. Wistuba, J. Wolf, Y.L. Wu, S.R. Yang, J.C.H. Yang, Y. Yatabe, G. Pentheroudakis, S. Peters, and Pulmonary Medicine

Subjects
Consensus, Lung Neoplasms, treatment, EGFR, Hematology, targeted therapy, Medical Oncology, testing, ErbB Receptors, lung cancer, Oncology, SDG 3 - Good Health and Well-being, consensus, Carcinoma, Non-Small-Cell Lung, Humans
Abstract

The European Society for Medical Oncology (ESMO) held a virtual consensus-building process on epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer in 2021. The consensus included a multidisciplinary panel of 34 leading experts in the management of lung cancer. The aim of the consensus was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where the available evidence is either limited or conflicting. The main topics identified for discussion were: (i) tissue and biomarkers analyses; (ii) early and locally advanced disease; (iii) metastatic disease and (iv) clinical trial design, patient's perspective and miscellaneous. The expert panel was divided into four working groups to address questions relating to one of the four topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the recommendations developed, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation.

Published
2022
Full Text
View/download PDF

33. Outcomes with durvalumab after chemoradiotherapy in stage IIIA-N2 non-small-cell lung cancer: an exploratory analysis from the PACIFIC trial

Author

S, Senan, M, Özgüroğlu, D, Daniel, A, Villegas, D, Vicente, S, Murakami, R, Hui, C, Faivre-Finn, L, Paz-Ares, Y L, Wu, H, Mann, P A, Dennis, S J, Antonia, Radiation Oncology, and CCA - Cancer Treatment and quality of life

Subjects
Cancer Research, Lung Neoplasms, multimodality therapy, Antibodies, Monoclonal, Chemoradiotherapy, chemotherapy, radiation therapy, surgery, Oncology, Carcinoma, Non-Small-Cell Lung, Disease Progression, Humans, immunotherapy
Abstract

Background: The phase III PACIFIC trial (NCT02125461) established consolidation durvalumab as standard of care for patients with unresectable, stage III non-small-cell lung cancer (NSCLC) and no disease progression following chemoradiotherapy (CRT). In some cases, patients with stage IIIA-N2 NSCLC are considered operable, but the relative benefit of surgery is unclear. We report a post hoc, exploratory analysis of clinical outcomes in the PACIFIC trial, in patients with or without stage IIIA-N2 NSCLC. Materials and methods: Patients with unresectable, stage III NSCLC and no disease progression after ≥2 cycles of platinum-based, concurrent CRT were randomized 2: 1 to receive durvalumab (10 mg/kg intravenously; once every 2 weeks for up to 12 months) or placebo, 1-42 days after CRT. The primary endpoints were progression-free survival (PFS; assessed by blinded independent central review according to RECIST version 1.1) and overall survival (OS). Treatment effects within subgroups were estimated by hazard ratios (HRs) from unstratified Cox proportional hazards models. Results: Of 713 randomized patients, 287 (40%) had stage IIIA-N2 disease. Baseline characteristics were similar between patients with and without stage IIIA-N2 NSCLC. With a median follow-up of 14.5 months (range: 0.2-29.9 months), PFS was improved with durvalumab versus placebo in both patients with [HR = 0.46; 95% confidence interval (CI), 0.33-0.65] and without (HR = 0.62; 95% CI 0.48-0.80) stage IIIA-N2 disease. Similarly, with a median follow-up of 25.2 months (range: 0.2-43.1 months), OS was improved with durvalumab versus placebo in patients with (HR = 0.56; 95% CI 0.39-0.79) or without (HR = 0.78; 95% CI 0.57-1.06) stage IIIA-N2 disease. Durvalumab had a manageable safety profile irrespective of stage IIIA-N2 status. Conclusions: Consistent with the intent-to-treat population, treatment benefits with durvalumab were confirmed in patients with stage IIIA-N2, unresectable NSCLC. Prospective studies are needed to determine the optimal treatment approach for patients who are deemed operable.

Published
2022
Full Text
View/download PDF

34. Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN

Author

L. Paz-Ares, Y. Chen, N. Reinmuth, K. Hotta, D. Trukhin, G. Statsenko, M.J. Hochmair, M. Özgüroğlu, J.H. Ji, M.C. Garassino, O. Voitko, A. Poltoratskiy, E. Musso, L. Havel, I. Bondarenko, G. Losonczy, N. Conev, H. Mann, T.B. Dalvi, H. Jiang, and J.W. Goldman

Subjects
Cancer Research, Lung Neoplasms, Oncology, Antineoplastic Combined Chemotherapy Protocols, Antibodies, Monoclonal, Humans, Antibodies, Monoclonal, Humanized, Small Cell Lung Carcinoma, Etoposide, Platinum
Abstract

In the phase III CASPIAN study, first-line durvalumab in combination with etoposide plus either cisplatin or carboplatin (EP) significantly improved overall survival (OS) versus EP alone in extensive-stage small-cell lung cancer (ES-SCLC). Durvalumab plus tremelimumab plus EP numerically improved OS versus EP, but did not reach statistical significance. Here we report updated OS in censored patients after median follow-up of3 years.805 patients with treatment-naïve ES-SCLC were randomized 1 : 1 : 1 to durvalumab plus EP, durvalumab plus tremelimumab plus EP, or EP. The two primary endpoints were OS for durvalumab plus EP versus EP and for durvalumab plus tremelimumab plus EP versus EP.As of 22 March 2021 (median follow-up 39.4 months, 86% maturity), durvalumab plus EP continued to demonstrate improved OS versus EP: hazard ratio (HR) 0.71 [95% confidence interval (CI) 0.60-0.86; nominal P = 0.0003]; median OS was 12.9 versus 10.5 months, and 36-month OS rate was 17.6% versus 5.8%. Durvalumab plus tremelimumab plus EP continued to numerically improve OS versus EP: HR 0.81 (95% CI: 0.67-0.97; nominal P = 0.0200); median OS was 10.4 months, and 36-month OS rate was 15.3%. Twenty-seven and nineteen patients in the durvalumab plus EP and durvalumab plus tremelimumab plus EP arms, respectively, remained on durvalumab treatment at data cut-off.Three times more patients were estimated to be alive at 3 years when treated with durvalumab plus EP versus EP, with the majority still receiving durvalumab at data cut-off, further establishing durvalumab plus EP as first-line standard of care for ES-SCLC.

Published
2022

36. 76P Safety profile of adjuvant pembrolizumab (pembro) in melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC): Pooled analysis of phase III clinical trials

Author

J.J. Luke, G.V. Long, C. Robert, M.S. Carlino, T.K. Choueiri, N.B. Haas, M.E.R. O'Brien, L. Paz-Ares, S. Peters, T.B. Powles, M.A. Leiby, J. Lin, Y. Zhao, C. Krepler, R.F. Perini, M.C. Pietanza, A. Samkari, T. Gruber, N. Ibrahim, and A.M.M. Eggermont

Subjects
Oncology, Immunology and Allergy
Published
2022
Full Text
View/download PDF

39. 1549TiP DeLLphi-303: Phase Ib first-line combination study of tarlatamab, a DLL3-targeting half-life extended bispecific T-cell engager (HLE BiTE®), with carboplatin, etoposide, and PD-L1 inhibition in extensive stage small cell lung cancer (ES-SCLC)

Author

S.M. Gadgeel, J. Al-Mondhiry, M-J. Ahn, S-W. Kim, L. Paz-Ares, H. Prenen, M. Boyer, J.G. Bustamante Alvarez, B. Solomon, S. Huang, M. Minocha, M. Kistler, and N. Hashemi Sadraei

Subjects
Oncology, Hematology
Published
2022
Full Text
View/download PDF

41. EP16.03-011 The European Program for ROutine Testing of Patients with Advanced Lung Cancer (EPROPA) 1 Year Activity

Author

F. Passiglia, L. Righi, A. Listì, F. Tabbò, P. Bironzo, M.L. Reale, C. Sini, S. Vallone, F. Arizio, M.V. Pacchiana Parravicini, L. Mazilu, H. Linardou, E. Roca, L. Buffoni, K. Mohorcic, V. Barbieri, D. Pignataro, A. Araujo, L. Paz Ares, E. Felip, N. Secen, A. Comanescu, E. Szmytke, G. Scagliotti, and S. Novello

Subjects
Pulmonary and Respiratory Medicine, Oncology
Published
2022
Full Text
View/download PDF

45. 1049P Clinical outcomes in patients (pts) with tumor PD-L1 < 1% with first-line (1L) nivolumab (NIVO) + ipilimumab (IPI) + 2 cycles of chemotherapy (chemo) vs chemo alone for metastatic NSCLC (mNSCLC): Results from CheckMate 9LA

Author

T. John, T-E. Ciuleanu, M. Cobo Dols, M. Schenker, B. Zurawski, J. Menezes, E.A. Richardet, J. Bennouna, Y. Cheng, E. Felip, O.J. Juan Vidal, A. Alexandru, L. Paz-Ares, S. Lu, M. Reck, N. Hu, X. Zhang, D.J. Grootendorst, L. Eccles, and D.P. Carbone

Subjects
Oncology, Hematology
Published
2022
Full Text
View/download PDF

50. 75TiP Open-label, phase II study of tusamitamab ravtansine (SAR408701) in combination with pembrolizumab and with pembrolizumab + platinum-based chemotherapy +/− pemetrexed in patients with CEACAM5-positive nonsquamous NSCLC (CARMEN-LC05)

Author

L. Paz-Ares, S. Parakh, J. Park, C. Rojas, F. Orlandi, R. Veillon, N. Isambert, T. Nagy, V. Muller, B. Medgyasszay, D. Rodriguez-Abreu, A. Fernandez, A. Puaud, S. Bensfia, N. Yang, and A. Spira

Subjects
Oncology, Hematology
Published
2022
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results