47 results on '"C. Wesseler"'
Search Results
2. Efficacy of docetaxel plus ramucirumab as palliative second-line therapy following first-line chemotherapy plus immune-checkpoint-inhibitor combination treatment in patients with non-small cell lung cancer (NSCLC) UICC stage IV
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Wolfgang M. Brueckl, Gunther H. Wiest, C. Wesseler, Amanda Tufman, Petra Hoffknecht, Eckart Laack, Martin Reck, Jens Kollmeier, Achim Rittmeyer, Fabian Reich, Petros Christopoulos, Bernhard Ulm, Joachim H. Ficker, and Albrecht Stenzinger
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Oncology ,Chemotherapy ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,non-small cell lung cancer (NSCLC) ,medicine.disease ,medicine.disease_cause ,Angiogenesis inhibitor ,Ramucirumab ,Docetaxel ,Internal medicine ,medicine ,Clinical endpoint ,Original Article ,KRAS ,Lung cancer ,business ,medicine.drug - Abstract
Background Chemotherapy plus immune-checkpoint inhibitor (CTx+ICI) therapy has become the preferred 1st line treatment in patients with metastatic NSCLC without oncogenic driven mutations. However, the optimal subsequent 2nd line treatment is not defined and several alternatives exist. The purpose of this analysis was to evaluate the efficacy of 2nd line docetaxel plus ramucirumab (D+R) initiated after failure of 1st line CTx+ICI. Methods Retrospective data were collected during routine care from German thoracic oncology centers. Only patients who had received at least one course of 2nd line D+R were included. ORR, PFS, OS and numbers of courses of D+R were investigated with PFS after initiation of D+R being the primary endpoint. Results Seventy-seven patients met the inclusion criteria. 2nd line treatment with D+R achieved an ORR and DCR of 32.5% and 62.4%, respectively. Median PFS for 2nd line therapy was 3.9 months with a DOR of 6.4 months. Median OS of 15.5 and 7.5 months were observed from the start of 1st line therapy and 2nd line treatment, respectively. No unexpected toxicities occurred. Presence of KRAS mutations was associated with significantly worse median PFS to D+R (2.8 vs. 4.5 months in wild-type cases; P=0.021) and was an independent predictor of inferior PFS in multivariate analysis. Conclusions D+R is an effective and safe 2nd line treatment after failure of 1st line CTx+ICI irrespective of NSCLC histology. However, patients with a KRAS mutation did not benefit from D+R in terms of PFS and will require further investigations.
- Published
- 2021
3. 1325P Checkpoint inhibitor monotherapy in potentially study-eligible or non-study-eligible NSCLC patients in the German CRISP registry real-world cohort (AIO-TRK-0315)
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H-D. Hummel, B. Jaeschke, Martina Jänicke, Michael Thomas, J. Schröder, Martin Sebastian, A. Groth, Stefan Zacharias, C. Wesseler, Frank Griesinger, V. Petersen, C. Schumann, J. Wilke, S. Dörfel, A. Fleitz, A. Hipper, W. Eberhardt, Wilko Weichert, W. M. Brückl, and Jens Kern
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Oncology ,medicine.medical_specialty ,business.industry ,Immune checkpoint inhibitors ,Hematology ,language.human_language ,German ,Internal medicine ,Trk receptor ,Cohort ,language ,Medicine ,business - Published
- 2021
4. Integration of Tumor Mutation Burden and PD-L1 Testing in Routine Laboratory Diagnostics in Non-Small Cell Lung Cancer
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Lukas C. Heukamp, Balázs Jóri, S. Schatz, Eva-Maria Willing, Matthias Kröger, Harry J.M. Groen, Linda Diehl, Stefanie Schmidt, Markus Falk, Hayat Oum El Kheir Ramdani, Frank Griesinger, Markus Tiemann, C. Wesseler, Roopika Menon, Petra Hoffknecht, Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
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0301 basic medicine ,Oncology ,PD-L1 ,Cancer Research ,medicine.medical_specialty ,tumor mutational burden ,BLOCKADE ,NEOANTIGENS ,PHASE-1 ,medicine.disease_cause ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,IMMUNOHISTOCHEMISTRY ,Lung cancer ,immuno-oncology ,Mutation ,biology ,business.industry ,driver mutation ,Routine laboratory ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,routine diagnostics ,OPEN-LABEL ,EFFICACY ,Immune checkpoint ,respiratory tract diseases ,lung cancer ,1ST-LINE TREATMENT ,030104 developmental biology ,030220 oncology & carcinogenesis ,biology.protein ,NIVOLUMAB PLUS IPILIMUMAB ,Biomarker (medicine) ,Non small cell ,Antibody ,SENSITIVITY ,business - Abstract
In recent years, Non-small cell lung cancer (NSCLC) has evolved into a prime example for precision oncology with multiple FDA-approved &ldquo, precision&rdquo, drugs. For the majority of NSCLC lacking targetable genetic alterations, immune checkpoint inhibition (ICI) has become standard of care in first-line treatment or beyond. PD-L1 tumor expression represents the only approved predictive biomarker for PD-L1/PD-1 checkpoint inhibition by therapeutic antibodies. Since PD-L1-negative or low-expressing tumors may also respond to ICI, additional factors are likely to contribute in addition to PD-L1 expression. Tumor mutation burden (TMB) has emerged as a potential candidate, however, it is the most complex biomarker so far and might represent a challenge for routine diagnostics. We therefore established a hybrid capture (HC) next-generation sequencing (NGS) assay that covers all oncogenic driver alterations as well as TMB and validated TMB values by correlation with the assay (F1CDx) used for the CheckMate 227 study. Results of the first consecutive 417 patients analyzed in a routine clinical setting are presented. Data show that fast reliable comprehensive diagnostics including TMB and targetable alterations are obtained with a short turn-around time. Thus, even complex biomarkers can easily be implemented in routine practice to optimize treatment decisions for advanced NSCLC.
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- 2020
5. Treatment patterns of EGFR mt+ NSCLC IV patients: Real world data of the NOWEL network
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Lukas C. Heukamp, Markus Falk, Frank Griesinger, S. Sackmann, J. Roeper, K Wedeken, M Tiemann, C. Wesseler, and U Stropiep
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Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,business ,Real world data - Published
- 2020
6. A Randomized Phase III Study of Abemaciclib Versus Erlotinib in Patients with Stage IV Non-small Cell Lung Cancer With a Detectable KRAS Mutation Who Failed Prior Platinum-Based Therapy: JUNIPER
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Tuncay Göskel, Alan Y. Chiang, Fabrice Barlesi, Shun Lu, Gerard J. Oakley, Alexis B. Cortot, Helge Bischoff, Álvaro Taus, Keunchil Park, Jonathan W. Goldman, Nicolas Girard, C. Wesseler, Sameera R. Wijayawardana, Kellie Turner, Shawn T. Estrem, Ernest Nadal, Karla Hurt, Luis Paz-Ares, William J. John, Konstantin H. Dragnev, Manuel Cobo, Julien Mazieres, Marianna Koczywas, Anwar Hossain, and Ege Üniversitesi
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,abemaciclib ,medicine.disease_cause ,NSCLC ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Clinical endpoint ,KRAS ,neoplasms ,erloitinib ,Chemotherapy ,business.industry ,Hazard ratio ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Confidence interval ,respiratory tract diseases ,Clinical trial ,030104 developmental biology ,030220 oncology & carcinogenesis ,Toxicity ,Erlotinib ,business ,platinum-resistant ,medicine.drug - Abstract
Introduction JUNIPER compared the efficacy and safety of abemaciclib, a selective cyclin-dependent kinase 4 and 6 inhibitor, with erlotinib in patients with non-small cell lung cancer (NSCLC) harboring a Kirsten rat sarcoma (KRAS) mutation. Methods JUNIPER was a Phase III, multicenter, randomized, open-label trial of abemaciclib versus erlotinib in patients with stage IV NSCLC and a detectable mutation in codons 12 or 13 of the KRAS oncogene, who progressed after platinum-based chemotherapy and 1 additional therapy (could include immune checkpoint inhibitor therapy). Randomized patients (3:2) received either 200 mg abemaciclib twice daily or 150 mg erlotinib once daily with best supportive care until disease progression or unacceptable toxicity. the primary endpoint was overall survival (OS); secondary endpoints included overall response rate (ORR), progression-free survival (PFS), and safety. Results Between December 2014 and April 2017, 453 patients were randomly assigned to receive abemaciclib (N = 270) or erlotinib (N = 183). Median OS was 7.4 months (95% confidence interval [CI]: 6.5, 8.8) with abemaciclib and 7.8 months (95% CI: 6.4, 9.5) with erlotinib (hazard ratio [HR] = 0.968 [95% CI: 0.768, 1.219]; p = .77). Median PFS was 3.6 months (95% CI: 2.8, 3.8) with abemaciclib and 1.9 months (95% CI: 1.9, 2.0) with erlotinib (HR = 0.583 [95% CI: 0.470, 0.723]; p, Eli Lilly and CompanyEli Lilly, This study was funded by Eli Lilly and Company.
- Published
- 2020
7. Neues zur molekular gezielten Therapie
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C. Wesseler
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Pulmonary and Respiratory Medicine - Published
- 2017
8. P33.20 Evaluation of Combined Biomarker of Response to Immunotherapy in Patients with Advanced Non-Small Cell Lung Cancer
- Author
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Frank Griesinger, C. Wesseler, Lukas C. Heukamp, Ed Schuuring, H. Ramdani, Markus Tiemann, Hendricus Groen, Markus Falk, and S. Schatz
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Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Immunotherapy ,medicine.disease ,Internal medicine ,medicine ,Biomarker (medicine) ,In patient ,Non small cell ,Lung cancer ,business - Published
- 2021
9. Erfolgreiche interventionelle Embolisation einer schweren pulmonalen Blutung bei Pulmonalarterienagenesie mit ausgeprägter Kollateralbildung
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S Schwarz, GH Wiest, W Gross-Fengels, S Meierling, C Petermann, E Atug, and C Wesseler
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Pulmonary and Respiratory Medicine - Published
- 2017
10. Das maligne epitheloide Haemangioendotheliom (EHE) der Lunge – 2 Fälle einer seltenen Tumorentität ohne etablierte Therapiestandards
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C Geuchen, C Wesseler, HO Winzer, W Gross-Fengels, and GH Wiest
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Pulmonary and Respiratory Medicine - Published
- 2017
11. PET – positive Herde beidseits: Oligo – metastasiert? Synchrone/Metachrone Bronchialkarzinome?
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S Meierling, C Petermann, D Gökce-Gün, C Wesseler, W Gross-Fengels, and GH Wiest
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Pulmonary and Respiratory Medicine - Published
- 2017
12. Design der JUNIPER Studie auf Grundlage der Phase 1 Daten zu Abemaciclib: Eine randomisierte Phase 3 Studie zum Vergleich von Abemaciclib versus Erlotinib bei NSCLC im Stadium IV mit nachgewiesener KRAS mutation
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Edward M. Chan, A Patnaik, AW Tolcher, Lee S. Rosen, C. Kropf-Sanchen, L Wunderle, Jonathan W. Goldman, Geoffrey I. Shapiro, Luis Paz-Ares, Achim Rittmeyer, Martin Reck, G Schmid-Bindert, and C Wesseler
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Pulmonary and Respiratory Medicine - Published
- 2017
13. Risk of not receiving 2nd line therapy is high in EGFR mt+ patients: Real world data of certified lung cancer centers on treatment sequence in EGFR mt+ patients
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Frank Griesinger, Markus Tiemann, Gunther H. Wiest, S. Sackmann, Markus Falk, D. Ukena, C. Wesseler, S. Schatz, J. Roeper, and Lukas C. Heukamp
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Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Medicine ,Treatment sequence ,Line (text file) ,business ,Lung cancer ,medicine.disease ,Real world data - Published
- 2019
14. P74.02 Treatment Patterns of EGFR mt+ NSCLC IV pts: Real World Data of the NOWEL Network
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S. Sackmann, Markus Tiemann, Gunther H. Wiest, Lukas C. Heukamp, Frank Griesinger, C. Wesseler, Markus Falk, D. Ukena, and J. Roeper
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Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Medicine ,business ,Real world data - Published
- 2021
15. 1912TiP NICITA: Nivolumab with chemotherapy in pleural mesothelioma after surgery
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J. Jürgens, S. Sackmann, Mark Kriegsmann, C. Wesseler, Helge Bischoff, M. de Wit, Michael Ried, Marc A Schneider, Harland S. Winter, Cornelius F. Waller, Martin Reck, Martin E. Eichhorn, Niels Reinmuth, T. Wehler, Manuel Feißt, Michael Thomas, H.-G. Kopp, Rajiv Shah, Daniel C. Christoph, and Laura V. Klotz
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Oncology ,medicine.medical_specialty ,Chemotherapy ,business.industry ,Pleural mesothelioma ,Internal medicine ,medicine.medical_treatment ,medicine ,Hematology ,Nivolumab ,business - Published
- 2020
16. Efficacy of Docetaxel Plus Ramucirumab as Palliative Third-Line Therapy Following Second-Line Immune-Checkpoint-Inhibitor Treatment in Patients With Non-Small-Cell Lung Cancer Stage IV
- Author
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Bernhard Ulm, Achim Rittmeyer, Fabian Reich, Petra Hoffknecht, Amanda Tufman, Jens Kollmeier, Petros Christopoulos, Joachim H. Ficker, Eckart Laack, Martin Reck, Gunther H. Wiest, C. Wesseler, and Wolfgang M. Brueckl
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Oncology ,medicine.medical_specialty ,ramucirumab ,medicine.medical_treatment ,Immune checkpoint inhibitors ,immune checkpoint inhibitor ,lcsh:RC254-282 ,Ramucirumab ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Internal medicine ,medicine ,In patient ,030212 general & internal medicine ,Lung cancer ,Chemotherapy ,business.industry ,palliative treatment ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Angiogenesis inhibitor ,angiogenesis inhibitor ,Docetaxel ,030220 oncology & carcinogenesis ,Original Article ,business ,medicine.drug - Abstract
Background: Antiangiogenic agents have been shown to stimulate the immune system and cause synergistic effects with chemotherapy. Effects might be even stronger after immune-checkpoint-inhibitor (ICI) therapy. The purpose of this analysis was to evaluate the efficacy of ramucirumab plus docetaxel (R + D) as third-line treatment after failure of a first-line platinum-based chemotherapy and a second-line ICI treatment in patients with non-small-cell lung cancer (NSCLC) stage IV. Methods: Retrospective data were collected from 9 German thoracic oncology centers. Only patients who had received at least 1 cycle of third-line R + D were included. The numbers of cycles, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were investigated. Results: Sixty-seven patients met the criteria for inclusion. Third-line treatment with R + D achieved an ORR of 36% and a disease control rate (DCR) of 69%. Median PFS for third-line therapy was 6.8 months with a duration of response (DOR) of 10.2 months. A median OS of 29 months was observed from the start of first-line therapy with a median OS of 11.0 months from the start of third-line treatment. No unexpected toxicities occurred. Conclusion: R + D is a highly effective and safe third-line treatment after failure of second-line programmed cell death protein 1/programmed cell death-ligand 1 (PD1/PD-L1)-derived ICI therapy irrespective of NSCLC histology. As there may be synergistic effects of second- and third-line treatments, this sequence is a very suitable option for patients not treated with first-line ICI. In addition, R + D should continue to be investigated as a second-line treatment option after failure of chemotherapy plus ICI in the palliative first–line treatment.
- Published
- 2020
17. Immunotherapeutic maintenance treatment with toll-like receptor 9 agonist lefitolimod in patients with extensive-stage small-cell lung cancer: results from the exploratory, controlled, randomized, international phase II IMPULSE study
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Oliver Schmalz, K.-P. Fröhling, E. Wiegert, Martin Wolf, Rumo Leistner, Wolfgang Blau, Hans-Georg Kopp, C. Wesseler, Claudia Mauri, W. M. Brückl, Christian Herzmann, Jens Kollmeier, Kerstin Kapp, Veerle Surmont, Parvis Sadjadian, Monika Serke, Michael Thomas, A. Navarro, M. Domine Gomez, Christian Brandts, Burghardt Wittig, Yolanda Garcia Garcia, Christina Grah, Lothar Müller, Georg Pall, Maria Rosario Garcia Campelo, Santiago Ponce-Aix, Frank Griesinger, J. Riera-Knorrenschild, Michael Schmidt, José Manuel Trigo Perez, Michael Schröder, A. Meyer, Léon Bosquee, Christian Wilfried Scholz, Rudolf M. Huber, and Paul Germonpré
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,Thoracic Tumors ,Population ,lefitolimod ,law.invention ,Carboplatin ,Maintenance Chemotherapy ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Maintenance therapy ,Randomized controlled trial ,law ,TLR9 agonist ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Lung cancer ,education ,Survival rate ,Etoposide ,education.field_of_study ,business.industry ,Hazard ratio ,Cancer ,International Agencies ,SCLC ,Hematology ,Original Articles ,medicine.disease ,Prognosis ,Chemotherapy regimen ,Small Cell Lung Carcinoma ,Survival Rate ,030104 developmental biology ,030220 oncology & carcinogenesis ,Toll-Like Receptor 9 ,immunotherapy ,Cisplatin ,business ,Immunosuppressive Agents ,Leflunomide ,Follow-Up Studies - Abstract
Background The immune surveillance reactivator lefitolimod (MGN1703), a DNA-based TLR9 agonist, might foster innate and adaptive immune response and thus improve immune-mediated control of residual cancer disease. The IMPULSE phase II study evaluated the efficacy and safety of lefitolimod as maintenance treatment in extensive-stage small-cell lung cancer (ES-SCLC) after objective response to first-line chemotherapy, an indication with a high unmet medical need and stagnant treatment improvement in the last decades. Patients and methods 103 patients with ES-SCLC and objective tumor response (as per RECIST 1.1) following four cycles of platinum-based first-line induction therapy were randomized to receive either lefitolimod maintenance therapy or local standard of care at a ratio of 3 : 2 until progression or unacceptable toxicity. Results From 103 patients enrolled, 62 were randomized to lefitolimod, 41 to the control arm. Patient demographics and response patterns to first-line therapy were balanced. Lefitolimod exhibited a favorable safety profile and pharmacodynamic assessment confirmed the mode-of-action showing a clear activation of monocytes and production of interferon-gamma-induced protein 10 (IP-10). While in the intent-to-treat (ITT) population no relevant effect of lefitolimod on progression-free and overall survival (OS) could be observed, two predefined patient subgroups indicated promising results, favoring lefitolimod with respect to OS: in patients with a low frequency of activated CD86+ B cells (hazard ratio, HR 0.53, 95% CI: 0.26–1.08; n = 38 of 88 analyzed) and in patients with reported chronic obstructive pulmonary disease (COPD) (HR 0.48, 95% CI: 0.20–1.17, n = 25 of 103). Conclusions The IMPULSE study showed no relevant effect of lefitolimod on the main efficacy end point OS in the ITT, but (1) the expected pharmacodynamic response to lefitolimod, (2) positive OS efficacy signals in two predefined subgroups and (3) a favorable safety profile. These data support further exploration of lefitolimod in SCLC.
- Published
- 2018
18. Treatment patterns of EGFR mt+ NSCLC IV pts: Real-world data of the NOWEL network
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Gunther H. Wiest, D. Ukena, S. Schatz, Frank Griesinger, J. Roeper, S. Sackmann, Markus Falk, Markus Tiemann, and C. Wesseler
- Subjects
0301 basic medicine ,medicine.medical_specialty ,business.industry ,Hematology ,Light smoker ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Baseline characteristics ,Family medicine ,Medicine ,business ,Real world data - Abstract
Background The percentage of pts switching from 1st gen TKI in 1st line to 3rd gen TKI in 2nd line seems to be low with 30% and it is questionable whether these data represent real world treatments. Therefore, we investigated the treatment pattern and especially the attrition rate between 1st and 2nd line therapy in EGFR mt+ pts from the NOWEL network. Methods A retrospective study of 1539 pts with non-squamous NSCLC IV was accomplished. 965/1536 (63%) pts were tested for EGFR mt+ between 2009-2018. 148/965 (15%) pts with an EGFR mt+ were identified. To calculate PFS and OS we used Kaplan Meier methods and the log rang test for p-values. Results Baseline characteristics of 148 EGFR mt+ pts: median age 65 yrs; 64% female (n = 95/148); 64% never/light smoker (n = 94/148). 135/148 pts (91%) carried an EGFR mt+ either del19 (n = 81) or L858R (n = 55). 144/148 pts were treated with TKI on 1st or 2nd line (after chemotherapy) and 4 pts received no therapy at all. 14/144 pts are still on 1st line, 9 pts were lost to follow-up and 3 pts died while on 1st line therapy. We identified 118/144 candidates for 2nd line therapy (because of progression on 1st line TKI) and only 84/118 (70%) pts received a 2nd line therapy. 30% (36/118) of pts did not receive a 2nd line therapy because of bad PS (n = 26), pts refusal (n = 2), fast progression (n = 6) and death (n = 2). After accessibility of 3rd gen TKI 72 pts were candidates for 2nd line treatment and 51/71 pts (71%) received a 2nd line therapy. MOS of pts receiving 2nd line therapy after access to 3rd gen TKI was 35 mo for pts with 2nd line therapy vs. 10 mo without 2nd line (p Conclusions In real world, a significant number of pts treated with 1st or 2nd gen TKI do not reach 2nd line therapy even with broad accessibility of 3rd gen TKI. Reasons for not receiving 2nd line therapy are in most cases deterioration of PS, death and no testing for T790M in a minority of cases. These data are important for the interpretation of the OS data of the FLAURA study as they reflect real world treatment algorithms in dedicated German lung cancer centers. Legal entity responsible for the study Carl v. Ossietzky University of Oldenburg, Prof. Dr. Griesinger. Funding Has not received any funding. Disclosure J. Roeper: Honoraria (self): Boehringer Ingelheim; Honoraria (self): Roche; Honoraria (self): AstraZeneca. M. Falk: Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Boehriger Ingelheim; Honoraria (self): Roche; Honoraria (self): AstraZeneca. M. Tiemann: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy: Boehriger Ingelheim; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Roche ; Honoraria (self): AstraZeneca. F. Griesinger: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Boehriger Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Celegene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Takeda; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Siemens; Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: Bayer. All other authors have declared no conflicts of interest.
- Published
- 2019
19. A randomized phase 3 study of abemaciclib versus erlotinib in previously treated patients with stage IV NSCLC with KRAS mutation: JUNIPER
- Author
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Álvaro Taus, Alexis B. Cortot, C. Wesseler, Jonathan W. Goldman, Manuel Cobo, Julien Mazieres, William J. John, Luis Paz-Ares, Marianna Koczywas, Anwar Hossain, Shun Lu, Helge Bischoff, Alan Chiang, Nicolas Girard, Karla Hurt, Tuncay Göksel, Fabrice Barlesi, Konstantin H. Dragnev, Keunchil Park, Ernest Nadal, and Ege Üniversitesi
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,endocrine system diseases ,Phases of clinical research ,medicine.disease_cause ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,neoplasms ,Abemaciclib ,biology ,business.industry ,biology.organism_classification ,respiratory tract diseases ,030104 developmental biology ,chemistry ,[No Keyword] ,030220 oncology & carcinogenesis ,Erlotinib ,Juniper ,KRAS ,Stage iv ,Previously treated ,business ,Kras mutation ,medicine.drug - Abstract
WOS:000442916003199, [No Abstract Available]
- Published
- 2018
20. P1.01-82 Risk of Not Receiving 2nd Line Therapy is High in EGFR mt+ pts: Real World Data of Certified Lung Cancer Centers on Treatment Sequence in EGFR mt+ pts
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Markus Tiemann, C. Wesseler, S. Sackmann, Gunther H. Wiest, Lukas C. Heukamp, Markus Falk, Frank Griesinger, S. Schatz, J. Roeper, and D. Ukena
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Treatment sequence ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,030212 general & internal medicine ,Line (text file) ,business ,Lung cancer ,Real world data - Published
- 2018
21. Impact on OS and PFS of 2nd and 3 rd Generation TKI in EGFR mt+ and ALK+ patients: Results of the NOWEL network
- Author
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Lukas C. Heukamp, D. Ukena, Gunther H. Wiest, C. Wesseler, Markus Tiemann, S. Schatz, N. Neemann, S. Sackmann, J. Roeper, Frank Griesinger, A Lüers, Maria Netchaeva, and Markus Falk
- Subjects
Pulmonary and Respiratory Medicine - Published
- 2018
22. Risk of not receiving second-line therapy is high in EGFR mt+ patients: Real-world data of certified lung cancer centers on treatment sequence in EGFR mt+ patients
- Author
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J. Roeper, Lukas C. Heukamp, Gunther H. Wiest, S. Sackmann, Markus Falk, D. Ukena, C. Wesseler, S. Schatz, Frank Griesinger, Anne Christina Lueers, and Markus Tiemann
- Subjects
Oncology ,medicine.medical_specialty ,Second-line therapy ,business.industry ,Internal medicine ,medicine ,Hematology ,Treatment sequence ,Lung cancer ,medicine.disease ,business ,Real world data - Published
- 2019
23. P2.03b-022 Outcome in Molecularly Defined NSCLC within the NOWEL Network: The Influence of Sequential 2nd and 3rd Generation TKI in EGFR mt+ and ALK+ pts
- Author
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Lukas C. Heukamp, Maria Netchaeva, J. Roeper, D. Ukena, U Stropiep, C. Wesseler, Gunther H. Wiest, Markus Tiemann, Nicole Neemann, S. Sackmann, Cora Hallas, Markus Falk, Frank Griesinger, and Anne Christina Lueers
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,business ,Outcome (game theory) - Published
- 2017
24. Risk of not receiving 2nd line therapy is high in EGFR mt+ pts: Real world data of certified lung cancer centers on treatment sequence in EGFR mt+ pts
- Author
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Gunther H. Wiest, S. Sackmann, Markus Falk, Lukas C. Heukamp, Markus Tiemann, Frank Griesinger, D. Ukena, C. Wesseler, and J. Roeper
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Treatment sequence ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Osimertinib ,Line (text file) ,business ,Lung cancer ,Real world data - Abstract
e21220Background: Recently FLAURA study demonstrated significant PFS and numeric OS benefit for Osimertinib 1st line vs. 1st gen. TKI’s. The number of pts switching from 1st gen. to 3rd gen. TKI (3...
- Published
- 2018
25. 163P The influence of 2nd and 3rd generation TKI in EGFR mt+ and ALK+ patients on OS and PFS: Results of the NOWEL network
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Markus Tiemann, J. Roeper, D. Ukena, Gunther H. Wiest, Frank Griesinger, C. Wesseler, S. Sackmann, Anne Christina Lueers, Maria Netchaeva, and Markus Falk
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,business - Published
- 2018
26. Immuncheckpointinhibition als Therapieoption bei einschmelzenden Nichtkleinzelligen Lungenkarzinomen
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C Petermann, S Schwarz, C Wesseler, W Groß-Fengels, GH Wiest, S Meierling, and I Pink
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Pulmonary and Respiratory Medicine - Published
- 2018
27. P3.01-038 Impact on OS and PFS of 2nd and 3rd Generation TKI in EGFR Mt+ and ALK+ Patients: Results of the NOWEL Network
- Author
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C. Wesseler, Lukas C. Heukamp, Gunther H. Wiest, S. Sackmann, J. Roeper, Nicole Neemann, Markus Tiemann, Frank Griesinger, Cora Hallas, Markus Falk, Maria Netchaeva, Anne Christina Lueers, and D. Ukena
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Medicine ,business ,Nuclear medicine - Published
- 2017
28. Impact on OS and PFS of 2nd and 3rd generation TKI in EGFR mt+ and ALK+ pts: Results of the NOWEL network
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Gunther H. Wiest, Markus Tiemann, S. Sackmann, Lukas C. Heukamp, Anne Christina Lueers, Frank Griesinger, J. Roeper, C Hallas, C. Wesseler, Markus Falk, Maria Netchaeva, D. Ukena, and N. Neemann
- Subjects
0301 basic medicine ,Oncology ,03 medical and health sciences ,medicine.medical_specialty ,030104 developmental biology ,0302 clinical medicine ,business.industry ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,Hematology ,business - Published
- 2017
29. Impact on OS of 2nd and 3rd generation TKI in EGFR mt+ and ALK+ patients: Results of the NOWEL network
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Lukas C. Heukamp, C. Wesseler, Markus Falk, U Stropiep, Frank Griesinger, D. Ukena, S. Sackmann, Markus Tiemann, Cora Hallas, Gunther H. Wiest, Nicole Neemann, J. Roeper, Maria Netchaeva, and Anne Christina Lueers
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,03 medical and health sciences ,0302 clinical medicine ,Clinical research ,030228 respiratory system ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Mutation testing ,business ,Stage iv - Abstract
e20560 Background: Available clinical research data shows that early mutation testing for patients with NSCLC stage IV could lead to an effective choice of therapy for patients with proven mutations. Targeted therapies achieve a higher ORR, PFS, OS and a better quality of life than chemotherapy in mt+ patients. With the advent of 2nd and 3rd generation TKI´s effective in 1st generation TKI resistant tumors, we wanted to study the impact of these drugs on the outcome of patients in a real life setting in 3 lung cancer centers. Methods: 1383 patients from the three cancer centers diagnosed with NSCLC stage IV (UICC 7) were examined. Methods for the detection of mutations included Sanger Sequencing, hybridization based COBAS testing as well as hybrid cage next generation sequencing. Results: 880/1383 (64%) consecutive patients with non-squamous cell NSCLC from the cancer centers were studied for the presence of tumor mutations, especially for EGFR and ALK mutations. The EGFR mutation rate was 16.6% (141/880), and the ALK-translocation rate 3.8% (24/635). Median OS in EGFR mt+ patients was 31 (n = 78) vs. 32 (n = 38) vs. 16 (n = 14) months respectively (center 1 vs. center 2 vs. center 3). Median OS in ALK mt+ patients was 25 (n = 17) months in center 1 and 11 (n = 5) months in center 2 (p < 0.05). Use of 3rd generation TKI Osimertinib (n = 17) lead to a significantly higher OS (n = 17, median OS 67 mo) than the use of only 1st and 2nd generation TKI (n = 113, median OS 24 mo, p < 0.000). Similarly, use of 2nd and 3rd generation ALKi impacted significantly on median OS: Crizotinib alone n = 7, 17 months, Crizotinib followed by Ceritinib and/or Brigatinib (n = 9) median OS not reached, p < 0.001. Conclusions: Smalldifferences in OS were observed, depending on the treatment centers, but the use of multiple EGFR and ALK-I impacted highly significantly on the outcome of patients with EGFR and ALK-alterations in a real life setting.
- Published
- 2017
30. Identification of therapeutically targetable genomic alterations in a cohort of patients with CUP using a hybrid-capture based next generation sequencing assay
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T. Langenbuch, J. Mueller, C. Brandts, Sotirios Lakis, Lukas C. Heukamp, A. Hube, C. Wesseler, Frank Griesinger, Roopika Menon, Johannes M. Heuckmann, Tilmann Bochtler, H. Loeffler, Alwin Krämer, and A.P. Garcia
- Subjects
Genetics ,Cancer Research ,Oncology ,Cohort ,Hybrid capture ,Identification (biology) ,Biology ,DNA sequencing - Published
- 2016
31. Rare inland reindeer lichens at Mima Mounds in southwest Washington State
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C. Marks-Fife, K. Hansen, D. Miller, B. Mead, C. Wesseler, J. McAlpine, K. Wesseler, Jared Streich, A. Ottombrino, S. Theis, Michele S. Wiseman, B. Chipman, N. Nolte, J. DiMeglio, K. Isch, S. Vandruff, Bruce McCune, Robert J. Smith, A. Corkery, G. Bono, T. Prior, and R. Arvidson
- Subjects
geography.geographical_feature_category ,Cladonia ,biology ,Ecology ,Rare species ,Plant Science ,Vegetation ,biology.organism_classification ,Geography ,Habitat ,Propagule ,Boreal ,Lichen ,Mima mounds - Abstract
Isolated populations of four reindeer lichen species and varieties co-occur in a unique relict prairie habitat at Mima Mounds Natural Area Preserve, southwest Washington State, USA. The prairie is the type locality for mima mounds, unusual geologic features providing topographical variation that influences vegetation patterns. Reindeer lichens ( Cladonia subgenus Cladina ) are usually more typical of northern boreal regions and are very rare in inland valley habitats of the western states outside of Alaska. Our study established distributional, ecological, chemotypic, and phylogenetic information for the target species. The species that at first appeared to be C. arbuscula was revealed by DNA sequences to be C. ciliata var. tenuis . We found that topography was not as important as recent fire history in explaining reindeer lichen distribution; in the future, prescribed fire is likely to benefit reindeer lichens so long as it preserves pockets of refugia as propagule sources. We also detected moderate air pollution stress, which is projected to have impacts on lichen abundances and community compositions in the near future. Chemotype analysis revealed 6 reindeer lichen chemotypes, of which 2 are rare (C. ciliata var. tenuis and C. portentosa subsp. pacifica f. decolorans ). Phylogenetic analyses supported previous species concepts, showing C. portentosa is distinct from the closely-related group that includes C. rangiferina and two varieties of C. ciliata . We synthesized our findings to provide a key for distinguishing the reindeer lichens of Mima Prairie. We suggested that rare inland reindeer lichens may benefit from small prescribed burns and sowing of propagules in disturbed areas, as well as continued monitoring and designation as state sensitive species.
- Published
- 2012
32. Outcome of First-Line Treatment With Pembrolizumab According to KRAS/TP53 Mutational Status for Nonsquamous Programmed Death-Ligand 1-High (≥50%) NSCLC in the German National Network Genomic Medicine Lung Cancer.
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Bischoff P, Reck M, Overbeck T, Christopoulos P, Rittmeyer A, Lüders H, Kollmeier J, Kulhavy J, Kemper M, Reinmuth N, Röper J, Janning M, Sommer L, Aguinarte L, Koch M, Wiesweg M, Wesseler C, Waller CF, Kauffmann-Guerrero D, Stenzinger A, Stephan-Falkenau S, Trautmann M, Lassmann S, Tiemann M, Klauschen F, Sebastian M, Griesinger F, Wolf J, Loges S, and Frost N
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- Humans, Male, Female, Aged, Retrospective Studies, Middle Aged, Germany, Antineoplastic Agents, Immunological therapeutic use, Aged, 80 and over, B7-H1 Antigen metabolism, B7-H1 Antigen genetics, Adult, Treatment Outcome, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Proto-Oncogene Proteins p21(ras) genetics, Antibodies, Monoclonal, Humanized therapeutic use, Tumor Suppressor Protein p53 genetics, Mutation
- Abstract
Introduction: Programmed death-ligand 1 expression currently represents the only validated predictive biomarker for immune checkpoint inhibition in metastatic NSCLC in the clinical routine, but it has limited value in distinguishing responses. Assessment of KRAS and TP53 mutations (mut) as surrogate for an immunosupportive tumor microenvironment (TME) might help to close this gap., Methods: A total of 696 consecutive patients with programmed death-ligand 1-high (≥50%), nonsquamous NSCLC, having received molecular testing within the German National Network Genomic Medicine Lung Cancer between 2017 and 2020, with Eastern Cooperative Oncology Group performance status less than or equal to 1 and pembrolizumab as first-line palliative treatment, were included into this retrospective cohort analysis. Treatment efficacy and outcome according to KRAS/TP53 status were correlated with TME composition and gene expression analysis of The Cancer Genome Atlas lung adenocarcinoma cohort., Results: Proportion of KRASmut and TP53mut was 53% (G12C 25%, non-G12C 28%) and 51%, respectively. In KRASmut patients, TP53 comutations increased response rates (G12C: 69.7% versus 46.5% [TP53mut versus wild-type (wt)], p = 0.004; non-G12C: 55.4% versus 39.5%, p = 0.03), progression-free survival (G12C: hazard ratio [HR] = 0.59, p = 0.009, non-G12C: HR = 0.7, p = 0.047), and overall survival (G12C: HR = 0.72, p = 0.16, non-G12C: HR = 0.56, p = 0.002), whereas no differences were observed in KRASwt patients. After a median follow-up of 41 months, G12C/TP53mut patients experienced the longest progression-free survival and overall survival (33.7 and 65.3 mo), which correlated with high tumor-infiltrating lymphocyte densities in the TME and up-regulation of interferon gamma target genes. Proinflammatory pathways according to TP53 status (mut versus wt) were less enhanced and not different in non-G12C and KRASwt, respectively., Conclusions: G12C/TP53 comutations identify a subset of patients with a very favorable long-term survival with immune checkpoint inhibitor monotherapy, mediated by highly active interferon gamma signaling in a proinflammatory TME., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)
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- 2024
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33. Mobocertinib in Patients with EGFR Exon 20 Insertion-Positive Non-Small Cell Lung Cancer (MOON): An International Real-World Safety and Efficacy Analysis.
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Illini O, Saalfeld FC, Christopoulos P, Duruisseaux M, Vikström A, Peled N, Demedts I, Dudnik E, Eisert A, Hashemi SMS, Janzic U, Kian W, Mohorcic K, Mohammed S, Silvoniemi M, Rothschild SI, Schulz C, Wesseler C, Addeo A, Armster K, Itchins M, Ivanović M, Kauffmann-Guerrero D, Koivunen J, Kuon J, Pavlakis N, Piet B, Sebastian M, Velthaus-Rusik JL, Wannesson L, Wiesweg M, Wurm R, Albers-Leischner C, Aust DE, Janning M, Fabikan H, Herold S, Klimova A, Loges S, Sharapova Y, Schütz M, Weinlinger C, Valipour A, Overbeck TR, Griesinger F, Jakopovic M, Hochmair MJ, and Wermke M
- Subjects
- Male, Humans, Female, Aged, ErbB Receptors genetics, Exons, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Aniline Compounds, Indoles, Pyrimidines
- Abstract
EGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis on patients with EGFR Ex20-positive NSCLC enrolled in a mobocertinib early access program. We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Data from 86 patients with a median age of 67 years and a median of two prior lines of treatment were analyzed. Treatment-related adverse events (TRAEs) occurred in 95% of patients. Grade ≥3 TRAEs were reported in 38% of patients and included diarrhea (22%) and rash (8%). In 17% of patients, therapy was permanently discontinued, and two patients died due to TRAEs. Women were seven times more likely to discontinue treatment than men. In the overall cohort, the objective response rate to mobocertinib was 34% (95% CI, 24-45). The response rate in treatment-naïve patients was 27% (95% CI, 8-58). The median progression-free and overall survival was 5 months (95% CI, 3.5-6.5) and 12 months (95% CI, 6.8-17.2), respectively. The intracranial response rate was limited (13%), and one-third of disease progression cases involved the brain. Mobocertinib also showed antitumor activity following EGFR Ex20-specific therapy and vice versa. Potential mechanisms of resistance to mobocertinib included amplifications in MET, PIK3CA, and NRAS. Mobocertinib demonstrated meaningful efficacy in a real-world setting but was associated with considerable gastrointestinal and cutaneous toxicity.
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- 2024
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34. [Criteria for inpatient diagnostic and treatment of patients with lung cancer, mesothelioma or thymoma].
- Author
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Frost N, Wesseler C, Wörmann B, and Eberhardt WEE
- Abstract
Competing Interests: Disclosure The authors report no conflicts of interest in this work.
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- 2024
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35. The phase I/II eNRGy trial: Zenocutuzumab in patients with cancers harboring NRG1 gene fusions.
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Kim DW, Schram AM, Hollebecque A, Nishino K, Macarulla T, Rha SY, Duruisseaux M, Liu SV, Al Hallak MN, Umemoto K, Wesseler C, Cleary JM, Springfeld C, Neuzillet C, Joe A, Jauhari S, Ford J, and Goto K
- Subjects
- Humans, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized adverse effects, Female, Carcinoma, Pancreatic Ductal genetics, Carcinoma, Pancreatic Ductal drug therapy, Carcinoma, Pancreatic Ductal pathology, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology, Neoplasms drug therapy, Neoplasms genetics, Male, Receptor, ErbB-3 genetics, Receptor, ErbB-2 genetics, Receptor, ErbB-2 antagonists & inhibitors, Receptor, ErbB-2 metabolism, Oncogene Proteins, Fusion genetics, Antineoplastic Agents, Immunological therapeutic use, Antineoplastic Agents, Immunological adverse effects, Adult, Middle Aged, Neuregulin-1 genetics, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology
- Abstract
Neuregulin 1 ( NRG1 ) fusions are oncogenic drivers that have been detected in non-small-cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC) and other solid tumors. NRG1 fusions are rare, occurring in less than 1% of solid tumors. Patients with NRG1 fusion positive (NRG1+) cancer have limited therapeutic options. Zenocutuzumab is a novel, bispecific IgG1 antibody that targets both HER2 and HER3 proteins and inhibits NRG1 binding through a 'Dock & Block
® ' mechanism of action. Here, we describe the rationale and design of the phase II component of the eNRGy trial, part of the overall, open-label phase I/II, multicenter trial exploring the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and antitumor activity of zenocutuzumab in patients with NRG1+ NSCLC, PDAC or other solid tumors.- Published
- 2024
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36. Checkpoint Inhibitor Monotherapy in Potentially Trial-Eligible or Trial-Ineligible Patients With Metastatic NSCLC in the German Prospective CRISP Registry Real-World Cohort (AIO-TRK-0315).
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Griesinger F, Sebastian M, Brueckl WM, Hummel HD, Jaeschke B, Kern J, Wesseler C, Jänicke M, Fleitz A, Zacharias S, Hipper A, Groth A, Weichert W, Dörfel S, Petersen V, Schröder J, Wilke J, Eberhardt WEE, and Thomas M
- Abstract
Introduction: Patients with metastatic NSCLC (mNSCLC) treated with immune checkpoint inhibitors in clinical practice may often not meet the strict inclusion criteria of clinical trials. Our aim was to assess the trial eligibility of patients with mNSCLC treated with pembrolizumab monotherapy in real-world and to compare the outcome of "trial-ineligible" and "potentially trial-eligible" patients., Methods: Data from the prospective, clinical research platform CRISP were used to compare patient characteristics, treatment, and outcome of patients with programmed cell death-ligand 1 tumor proportion score greater than or equal to 50% tumors treated with pembrolizumab monotherapy who are deemed either "potentially trial-eligible" or "trial-ineligible" according to inclusion and exclusion criteria of the registrational studies (KEYNOTE-024 and -042)., Results: Of 746 patients included, 343 patients (46.0%) were classified as "trial-ineligible" and had significantly worse outcomes compared with "potentially trial-eligible" patients (n = 403, 54.0%): median progression-free survival: 6.2 (95% confidence interval [CI]: 5.2-8.4) versus 10.3 (95% CI: 8.4-13.8) months, hazard ratio (trial-ineligible versus potentially trial-eligible) of 1.43 (95% CI: 1.19-1.72), p less than 0.001; median overall survival: 15.9 (95% CI: 11.4-20.3) versus 25.3 (95% CI: 19.8-30.4) months, hazard ratio of 1.36 (95% CI: 1.10-1.67), p equals 0.004., Conclusions: Our data reveal that a considerable proportion of patients with mNSCLC are not eligible to participate in a clinical trial and were found to have worse outcomes than potentially trial-eligible patients, whose outcomes were comparable with those obtained from pivotal clinical trials. This is of substantial clinical relevance for physicians discussing outcomes to be expected with their patients and stresses the need for real-world effectiveness analyses., Competing Interests: Dr. Griesinger has received support for the present manuscript (grants to the institution) from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Takeda. Furthermore, he has received grants (to the institution) from Amgen and Siemens; personal fees for consulting from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Takeda; payment for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Takeda; support for attending meetings and/or travel from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Takeda; and personal fees for participation on a data safety monitoring board or advisory board from Merck Sharp & Dohme. He declares an unpaid fiduciary role in the German Society of Hematology and Oncology (first author of Oncopedia recommendations) and in the German Cancer Society (S3 guidelines author). Dr. Sebastian has a consulting or advisory role and has received honoraria from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Janssen-Cilag, Eli Lilly, Merck Sharp & Dohme, Merck-Serono, Novartis, Pfizer, Roche, Takeda, and Tesaro; he has also received research funding from AstraZeneca. Dr. Brueckl has received personal fees and fees for lectures from AstraZeneca, Bristol-Myers Squibb, Boehringer, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, and Roche and fees for educational events from AstraZeneca, Boehringer, Eli Lilly, Pfizer, and Roche. Furthermore, he has received congress fees and personal fees from AstraZeneca, Boehringer, and Roche Pharma and has received personal fees and support for participation on advisory boards from AstraZeneca, Boehringer, Bristol-Myers Squibb, Eli Lilly Pharma, Novartis, Merck Sharp & Dohme and Roche. He declares a patent planned (EP21183549). Dr. Hummel has received personal fees as steering board member and fees for consulting from Amgen; has received personal fees for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Amgen, Bristol-Myers Squibb, and Boehringer Ingelheim; payment for expert testimony from Amgen and Boehringer Ingelheim; support for attending meetings and/or travel from Amgen and Bristol-Myers Squibb; and personal fees for participation on a data safety monitoring board or advisory board from Amgen and Boehringer Ingelheim. Dr. Kern has received support for attending meetings and/or travel from AstraZeneca, Merck Sharp & Dohme, Pfizer, and Roche and for participation on advisory boards from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Merck/Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Takeda. Dr. Wesseler has received honoraria for lectures and travel from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi, and Takeda. Dr. Hipper and Mrs. Groth have received research funding (to their employer AIO-Studien-gGmbH) from Amgen Ltd., AstraZeneca GmbH, Boehringer Ingelheim Pharma GmbH & Co. KG, Bristol-Myers Squibb GmbH & Co. KGaA, Celgene GmbH, GlaxoSmithKline Research & Development Limited, Janssen-Cilag GmbH, Eli Lilly Deutschland GmbH, Merck Sharp & Dohme GmbH, Novartis Pharma GmbH, Pfizer Pharma GmbH, Roche Pharma AG, and Takeda Pharma Vertriebs GmbH & Co. KG. Dr. Weichert has received research support (to the institution) from AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, and Roche; fees for consulting, travel support, fees for participation on advisory boards and lectures, and payment or honoraria for presentations, speakers bureaus, manuscript writing, or educational events from ADC, Agilent, Amgen, Astellas, AstraZeneca, Bayer, Boehringer, Bristol-Myers Squibb, Eisai, GlaxoSmithKline, Illumina, Janssen, Eli Lilly, Merck, Molecular Health, Merck Sharp & Dohme, Novartis, Pfizer, Siemens, Takeda, and Roche. Mr. Dörfel holds iOMEDICO shares. Dr. Schröder has received consulting fees from iOMEDICO, Celgene, Roche, Bristol-Myers Squibb, Clovis Oncology GmbH, GlaxoSmithKline, Boehringer Ingelheim, Amgen, Novartis, Merck Sharp & Dohme, AOP, Searchlight, Pharma Partner, Medixline GmbH, Eisai, HE Research GmbH, AbbVie, NIO, I+E Research, Octapharma and IPSEN. Further he declares honoraria from iOMEDICO, Celgene, Roche, Bristol-Myers Squibb, Clovis Oncology GmbH, GlaxoSmithKline, Boehringer Ingelheim, Amgen, Novartis, Merck Sharp & Dohme, AOP, Searchlight, Pharma Partner, Medixline GmbH, Eisai, HE Research GmbH, AbbVie, NIO, I+E Research, Octapharma, IPSEN, BeiGene, and Miltenyi. Dr. Eberhardt has received research funding (to the institution) from Eli Lilly, AstraZeneca, and Bristol-Myers Squibb; honoraria for advisory boards from Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Janssen-Cilag, Merck/Merck Sharp & Dohme, Roche, Pfizer, Novartis, Takeda, Boehringer Ingelheim, and AbbVie; and honoraria for lectures from Amgen, Baumgart Consult, Bristol-Myers Squibb, Merck/Merck Sharp & Dohme, Roche, Pfizer, Novartis, Takeda, Boehringer Ingelheim, and AbbVie. Dr. Thomas has received research funding (to the institution) from AstraZeneca, Bristol-Myers Squibb, Merck, Roche, and Takeda; personal fees for speakers bureaus and advisory boards from Amgen, AstraZeneca, Beigene, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Daiichi Sankyo, GlaxoSmithKline, Janssen Oncology, Eli Lilly, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi, and Takeda; and support for attending meetings and/or travel from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Janssen Oncology, Eli Lilly, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi, and Takeda. The remaining authors declare no conflict of interest., (© 2024 by the International Association for the Study of Lung Cancer.)
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- 2023
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37. High In-Hospital Mortality in SARS-CoV-2-Infected Patients with Active Cancer Disease during Omicron Phase of the Pandemic: Insights from the CORONA Germany Study.
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Konermann FM, Gessler N, Wohlmuth P, Behr J, Feldhege J, Gloeckner C, Gunawardene MA, Herrlinger KR, Hoelting T, Pape UF, Reinmuth N, Stang A, Sheikhzadeh S, Arnold D, and Wesseler C
- Subjects
- Adult, Humans, SARS-CoV-2, Hospital Mortality, Pandemics, Cohort Studies, Germany epidemiology, COVID-19, Neoplasms
- Abstract
Introduction: SARS-CoV-2 infected patients with cancer have a worse outcome including a significant higher mortality, compared to non-cancer patients. However, limited data are available regarding in-hospital mortality during the Omicron phase of the pandemic. Therefore, the aim of the study was the comparison of mortality in patients with history of cancer and patients with active cancer disease during the different phases of the COVID-19 pandemic, focusing on the current Omicron variant of concern., Methods: We conducted a multicenter, observational, epidemiological cohort study at 45 hospitals in Germany. Until July 20, 2022, all adult hospitalized SARS-CoV-2 positive patients were included. The primary endpoint was in-hospital mortality regarding cancer status (history of cancer and active cancer disease) and SARS-CoV-2 virus type., Results: From March 11, 2020, to July 20, 2022, a total of 27,490 adult SARS-CoV-2 positive patients were included in the study. 2,578 patients (9.4%) had diagnosis of cancer, of whom 1,065 (41.3%) had history of cancer, whereas 1,513 (58.7%) had active cancer disease. Overall 3,749 out of the total of 27,490 patients (13.6%) died during the hospital stay. Patients with active cancer disease had a significantly higher mortality compared to patients without cancer diagnosis, in both phases of the pandemic (wild-type to Delta: OR 1.940 [1.646-2.285]); Omicron: 2.864 [2.354-3.486]). After adjustment to co-variables, SARS-CoV-2 infected patients with active cancer disease had the highest risk for in-hospital mortality compared to the other groups, in both phases of the pandemic., Conclusion: The CORONA Germany study indicates that hospitalized patients with active cancer disease are at high risk of death during a SARS-CoV-2 infection. Mortality of patients with history of cancer improved to nearly the level of non-cancer patients during Omicron phase., (© 2023 S. Karger AG, Basel.)
- Published
- 2023
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38. Is Dementia Associated with COVID-19 Mortality? A Multicenter Retrospective Cohort Study Conducted in 50 Hospitals in Germany.
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Kostev K, Gessler N, Wohlmuth P, Arnold D, Bein B, Bohlken J, Herrlinger K, Jacob L, Koyanagi A, Nowak L, Smith L, Wesseler C, Sheikhzadeh S, and Wollmer MA
- Subjects
- Humans, COVID-19 Testing, Germany epidemiology, Hospitalization, Hospitals, Retrospective Studies, Mortality, COVID-19, Dementia
- Abstract
Background: Dementia has been identified as a major predictor of mortality associated with COVID-19., Objective: The objective of this study was to investigate the association between dementia and mortality in COVID-19 inpatients in Germany across a longer interval during the pandemic., Methods: This retrospective study was based on anonymized data from 50 hospitals in Germany and included patients with a confirmed COVID-19 diagnosis hospitalized between March 11, 2020 and July, 20, 2022. The main outcome of the study was the association of mortality during inpatient stays with dementia diagnosis, which was studied using multivariable logistic regression adjusted for age, sex, and comorbidities as well as univariate logistic regression for matched pairs., Results: Of 28,311 patients diagnosed with COVID-19, 11.3% had a diagnosis of dementia. Prior to matching, 26.5% of dementia patients and 11.5% of non-dementia patients died; the difference decreased to 26.5% of dementia versus 21.7% of non-dementia patients within the matched pairs (n = 3,317). This corresponded to an increase in the risk of death associated with dementia (OR = 1.33; 95% CI: 1.16-1.46) in the univariate regression conducted for matched pairs., Conclusion: Although dementia was associated with COVID-19 mortality, the association was weaker than in previously published studies. Further studies are needed to better understand whether and how pre-existing neuropsychiatric conditions such as dementia may impact the course and outcome of COVID-19.
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- 2023
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39. NSCLC with uncommon EGFR mutations treated with atezolizumab plus bevacizumab and chemotherapy.
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Trummer A, Bethge A, Dickgreber N, Dittrich I, Golpon H, Hoffknecht P, Overbeck TR, Wesseler C, and Reck M
- Subjects
- Humans, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bevacizumab therapeutic use, Mutation, Protein Kinase Inhibitors therapeutic use, Retrospective Studies, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, ErbB Receptors genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics
- Abstract
Objectives: For refractory NSCLC patients with EGFR mutations, recent studies have demonstrated a favorable response to the combination of anti-angiogenic therapy and checkpoint inhibition but included only very few patients with uncommon EGFR mutations for which treatment options are still limited despite new targeted treatments., Materials and Methods: Sixteen stage IV NSCLC patients with uncommon EGFR mutations from 9 different German centers were treated in first or further line with Atezolizumab, Bevacizumab, Carboplatin and (nab-)Paclitaxel (ABCP). PFS was evaluated from start of ABCP and OS from time of initial diagnosis of stage IV., Results: Patients with either an Exon 20 insertion (n = 9) or other uncommon EGFR mutations (n = 7) received ABCP in first, second or further line. Nine patients had received a TKI therapy in first line with an ORR of 66.7 % and a median time-to-next-treatment of 6.7 months. After a median number of 4 ABCP cycles, 4 patients (25.0 %) required a dose reduction of chemotherapy and 5 patients (31.3 %) suffered from grade 3 or 4 toxicity. Overall response rate was 81.3 % and disease control rate 87.5 %. 14 patients (87.5 %) received a maintenance with AB and the median follow-up after initial diagnosis was 24.3 months. Median PFS was 13.6 months for both the entire cohort and for Exon 20 insertions. Corresponding median OS was either not reached or 30.7 months. Landmark analysis at 12 months gave a PFS of 42.8 % and an OS of 93.3 %. Four patients were rechallenged with ABCP while progressing under maintenance and responded again. In further line therapy, clinical benefit was achieved in all of 3 patients receiving Amivantamab, but in only one of four patients receiving mobocertinib., Conclusion: In this retrospective analysis, ABCP achieves an encouraging outcome for patients with uncommon EGFR mutations and is a valuable option in the early treatment course., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AT, ND, ID, PH, TO, CW and MR have received honoraria or travel expenses from Roche/Genentech. MR is part of the Speakers Bureau of Roche/Genentech., (Copyright © 2022 Elsevier B.V. All rights reserved.)
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- 2022
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40. The impact of TP53 co-mutations and immunologic microenvironment on outcome of lung cancer with EGFR exon 20 insertions.
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Christopoulos P, Kluck K, Kirchner M, Lüders H, Roeper J, Falkenstern-Ge RF, Szewczyk M, Sticht F, Saalfeld FC, Wesseler C, Hackanson B, Dintner S, Faehling M, Kuon J, Janning M, Kauffmann-Guerrero D, Kazdal D, Kurz S, Eichhorn F, Bozorgmehr F, Shah R, Tufman A, Wermke M, Loges S, Brueckl WM, Schulz C, Misch D, Frost N, Kollmeier J, Reck M, Griesinger F, Grohé C, Hong JL, Lin HM, Budczies J, Stenzinger A, and Thomas M
- Subjects
- Brain Neoplasms genetics, Brain Neoplasms secondary, Exons, Humans, Mutation, Platinum therapeutic use, Protein Kinase Inhibitors therapeutic use, Retrospective Studies, Tumor Microenvironment genetics, Antineoplastic Agents therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, ErbB Receptors genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology, Tumor Suppressor Protein p53 genetics
- Abstract
Background: EGFR exon20 insertions (ex20ins) are targeted by novel compounds in non-small-cell lung cancer (NSCLC). However, data about outcome under conventional therapies and the influence of molecular features are scarce., Patients and Methods: We retrospectively analysed 118 patients with evaluation of radiologic response based on RECIST v1.1. TP53 status was available for 88 cases., Results: Platinum doublets and chemoimmunotherapy showed similar response rates (20-25%), disease control rates (80%) and median progression-free survival (mPFS, ≈7 months), which were longer compared to monochemotherapy (9%, 59%, 4.1 months), EGFR inhibitors (0%, 46%, 3.0) and PD-(L)1 inhibitors (0%, 30%, 2.1; p < 0.05). Overall survival (OS) was not dependent on the choice of first-line treatment, but related to more lines of systemic therapy (p < 0.05). TP53 mutations and brain metastases were associated with shorter PFS under platinum doublets and EGFR inhibitors (HR 3.3-6.1, p < 0.01), and shorter OS for patients receiving both treatments (p < 0.05). More tumour CD8
+ and less Th1 cells were associated with longer OS independent of brain and TP53 status (p < 0.01). No difference in outcome was noted according to the ex20ins site and use of pemetrexed (vs. other cytotoxics) or bevacizumab. Long-lasting responses (>1 year) occasionally occurred under EGFR inhibitors for both 'near-' and 'far-loop' variants., Conclusions: Platinum doublets and chemoimmunotherapy have the highest activity with ORR of 20-25% and mPFS of approximately 7 months, regardless of the cytotoxic partner, while PD-(L)1 inhibitors show limited efficacy. TP53 mutations, brain metastases and a lower tumour CD8/Th1-cell ratio are independently associated with shorter survival., Competing Interests: Conflict of interest statement PC: research funding from Amgen, AstraZeneca, Boehringer Ingelheim, Novartis, Roche, Takeda, and advisory board/lecture fees from AstraZeneca, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Gilead, Novartis, Pfizer, Roche, Takeda. JR: lecture fees from AstraZeneca, Boehringer Ingelheim. FCS: research funding from Roche; non-financial support from Lilly; personal fees from Takeda, and Pfizer, outside the submitted work. BH: advisory board/lecture fees from AstraZeneca, Boehringer Ingelheim, BMS, MSD, Roche, Pfizer. JK: research funding from AstraZeneca and Celgene. MJ: speaker's honoraria from Roche, Boehringer, and travel grants from Daiichi Sankyo. DK: advisory boards/speakers honoraria from AstraZeneca, BMS, Boehringer Ingelheim, GSK, MSD, Novartis, Pfizer, Roche, Takeda. FE: speaker's honoraria from Roche. FB: research funding from AstraZeneca, BMS and Roche, and travel grants from BMS and MSD. RS: research funding from BMS, and speaker's honoraria from AstraZeneca and Roche. AT: research funding from BMS. MW: research funding from Roche; Personal fees from Roche, AstraZeneca, Boehringer, Kite, Novartis, Merck, BMS, Heidelberg Pharma; Non-financial support from AstraZeneca, BMS, Glenmark; outside the submitted work. SL: advisory board, speaker's honoraria and travel support from BerGenBio, Novartis, Lilly, BMS, MSD, Roche, Celgene, Takeda, AstraZeneca, Sanofi, as well as research funding from Roche, BMS, BerGenBio. WB: consulting fees from AstraZeneca, Boehringer Ingelheim, BMS, Lilly, MSD, Pfizer, Roche, Sanofi, honoraria for lectures from AstraZeneca, Boehringer Ingelheim, BMS, Lilly, MSD, Pfizer, Roche, Sanofi. Travel grants from AstraZeneca, Boehringer Ingelheim, MSD, Roche. CS: advisory board honoraria from AstraZeneca, Boehringer Ingelheim, BMS, MSD, Novartis, Roche, Pfizer, Takeda. Speaker's honoraria from AstraZeneca, Boehringer, Lilly, Roche, MSD, Takeda. DM: advisory board/lecture fees from AstraZeneca, BMS, Boehringer Ingelheim, Lilly, MSD, Novartis, Roche, Sanofi and Takeda (no personal honoraria) NF: advisory board/lecture fees from AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Pfizer, Roche, MSD, Takeda. JK: advisory board member without receiving any personal fees for Roche Pharma, Boehringer Ingelheim, BMS, MSD, Amgen, Lilly and Takeda. MR: advisory board/lecture fees from Amgen, AstraZeneca, BMS, Boehringer, Lilly, Merck, MSD, Novartis, Pfizer, Roche, Samsung. FG: grants and personal fees from AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Novartis, Pfizer, Roche, Takeda, as well as personal fees from AbbVie, Tesaro/GSK, Blueprint Medicines, Amgen. CG: advisory board/lecture fees from Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Takeda, MSD, Novartis, Pfizer, Roche, AbbVie, Tesaro/GSK and Blueprints Medicines. AS: advisory board honoraria from BMS, AstraZeneca, ThermoFisher, Novartis, speaker's honoraria from BMS, Illumina, AstraZeneca, Novartis, ThermoFisher, MSD, Roche, and research funding from Chugai and BMS. MT: advisory board honoraria from Novartis, Eli Lilly, BMS, MSD, Roche, Celgene, Takeda, AbbVie, Boehringer Ingelheim, Pfizer, speaker's honoraria from Eli Lilly, MSD, Takeda, Pfizer, research funding from AstraZeneca, BMS, Celgene, Novartis, Roche, Takeda, and travel grants from BMS, MSD, Novartis, Boehringer. All remaining authors have declared no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)- Published
- 2022
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41. Immune related endonucleases and GTPases are not associated with tumor response in patients with advanced non-small cell lung cancer treated with checkpoint inhibitors.
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Ramdani HO, Falk M, Heukamp LC, Schatz S, Tiemann M, Wesseler C, Diehl L, Schuuring E, Groen HJM, and Griesinger F
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- 5'-Nucleotidase analysis, ADP-Ribosylation Factors analysis, Aged, Aged, 80 and over, Apyrase analysis, B7 Antigens analysis, Biomarkers, Tumor genetics, Carcinoma, Non-Small-Cell Lung enzymology, Carcinoma, Non-Small-Cell Lung immunology, Carcinoma, Non-Small-Cell Lung mortality, Disease Progression, Female, GPI-Linked Proteins analysis, Humans, Immunohistochemistry, Lung Neoplasms enzymology, Lung Neoplasms immunology, Lung Neoplasms mortality, Male, Middle Aged, Mutation, Predictive Value of Tests, Progression-Free Survival, Receptors, Cytoplasmic and Nuclear analysis, Time Factors, Antibodies, Monoclonal, Humanized therapeutic use, Biomarkers, Tumor analysis, Carcinoma, Non-Small-Cell Lung drug therapy, Immune Checkpoint Inhibitors therapeutic use, Lung Neoplasms drug therapy, Nivolumab therapeutic use
- Abstract
Immune related endonucleases have recently been described as potential therapeutic targets and predictors of response to treatment with immune checkpoint inhibitors (ICI). The aim is to evaluate the association between the expression of 5 biomarkers involved in the immune response (CD73, CD39, VISTA, Arl4d and Cytohesin-3) in parallel with the more common ICI-predictive markers, PD-L1 expression and Tumor Mutation Burden (TMB) with response to ICI therapy in an advanced non-small cell lung cancer (NSCLC) cohort., Methods: Patients with advanced NSCLC treated with ICI single agent were divided into responders and non-responders according to RECIST v1.1 and duration of response (DOR) criteria. Immunohistochemistry was performed on pretreatment tumor tissue samples for PD-L1, CD73, CD39, VISTA, Arl4d, and Cytohesin-3 expression. TMB was estimated with NEOplus v2 RUO (NEO New Oncology GmbH) hybrid capture next generation sequencing assay. Resistance mutations in STK11/KEAP1 and positive predictive mutations in ARID1A/POLE were also evaluated., Results: Included were 56 patients who were treated with ICI single agent. The median progression-free and overall survival for the whole cohort was 3.0 (95% CI, 2.4-3.6) and 15 (95% CI, 9.7-20.2) months, respectively. The distribution of CD73 in tumor cells and CD39, VISTA, Arl4d and Cytohesin-3 expression in immune cells were not different between responders and non-responders. Also, PD-L1 and TMB were not predictive for response. The frequency of STK11, KEAP1 and ARID1A mutations was low and only observed in the non-responder group., Conclusion: Separate and combined expression of 5 biomarkers involved in the immune response (CD73, CD39, VISTA, Arl4d, and Cytohesin-3) was not associated with response in our cohort of advanced NSCLC patients receiving single agent ICI. To confirm our findings the analysis of independent larger cohorts is warranted., (Copyright © 2021 The Authors. Published by Elsevier GmbH.. All rights reserved.)
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- 2021
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42. Prognostic Impact of Acute Cardiovascular Events in COVID-19 Hospitalized Patients-Results from the CORONA Germany Study.
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Gunawardene MA, Gessler N, Wohlmuth P, Heitmann K, Anders P, Jaquet K, Herborn CU, Arnold D, Bein B, Bergmann MW, Herrlinger KR, Stang A, Schreiber R, Wesseler C, and Willems S
- Abstract
Background: Acute myocardial injury (AMJ), assessed by elevated levels of cardiac troponin, is associated with fatal outcome in coronavirus disease 2019 (COVID-19). However, the role of acute cardiovascular (CV) events defined by clinical manifestation rather than sole elevations of biomarkers is unclear in hospitalized COVID-19 patients., Objective: The aim of this study was to investigate acute clinically manifest CV events in hospitalized COVID-19 patients., Methods: From 1 March 2020 to 5 January 2021, we conducted a multicenter, prospective, epidemiological cohort study at six hospitals from Hamburg, Germany (a portion of the state-wide 45-center CORONA Germany cohort study) enrolling all hospitalized COVID-19 patients. Primary endpoint was occurrence of a clinically manifest CV-event., Results: In total, 132 CV-events occurred in 92 of 414 (22.2%) patients in the Hamburg-cohort: cardiogenic shock in 10 (2.4%), cardiopulmonary resuscitation in 12 (2.9%), acute coronary syndrome in 11 (2.7%), de-novo arrhythmia in 31 (7.5%), acute heart-failure in 43 (10.3%), myocarditis in 2 (0.5%), pulmonary-embolism in 11 (2.7%), thrombosis in 9 (2.2%) and stroke in 3 (0.7%). In the Hamburg-cohort, mortality was 46% (42/92) for patients with a CV-event and 33% (27/83) for patients with only AMJ without CV-event (OR 1.7, CI: (0.94-3.2), p = 0.077). Mortality was higher in patients with CV-events (Odds ratio(OR): 4.8, 95%-confidence-interval(CI): [2.9-8]). Age (OR 1.1, CI: (0.66-1.86)), atrial fibrillation (AF) on baseline-ECG (OR 3.4, CI: (1.74-6.8)), systolic blood-pressure (OR 0.7, CI: (0.53-0.96)), potassium (OR 1.3, CI: (0.99-1.73)) and C-reactive-protein (1.4, CI (1.04-1.76)) were associated with CV-events., Conclusion: Hospitalized COVID-19 patients with clinical manifestation of acute cardiovascular events show an almost five-fold increased mortality. In this regard, the emergence of arrhythmias is a major determinant.
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- 2021
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43. Efficacy of docetaxel plus ramucirumab as palliative second-line therapy following first-line chemotherapy plus immune-checkpoint-inhibitor combination treatment in patients with non-small cell lung cancer (NSCLC) UICC stage IV.
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Brueckl WM, Reck M, Rittmeyer A, Kollmeier J, Wesseler C, Wiest GH, Christopoulos P, Stenzinger A, Tufman A, Hoffknecht P, Ulm B, Reich F, Ficker JH, and Laack E
- Abstract
Background: Chemotherapy plus immune-checkpoint inhibitor (CTx+ICI) therapy has become the preferred 1st line treatment in patients with metastatic NSCLC without oncogenic driven mutations. However, the optimal subsequent 2nd line treatment is not defined and several alternatives exist. The purpose of this analysis was to evaluate the efficacy of 2nd line docetaxel plus ramucirumab (D+R) initiated after failure of 1st line CTx+ICI., Methods: Retrospective data were collected during routine care from German thoracic oncology centers. Only patients who had received at least one course of 2nd line D+R were included. ORR, PFS, OS and numbers of courses of D+R were investigated with PFS after initiation of D+R being the primary endpoint., Results: Seventy-seven patients met the inclusion criteria. 2nd line treatment with D+R achieved an ORR and DCR of 32.5% and 62.4%, respectively. Median PFS for 2nd line therapy was 3.9 months with a DOR of 6.4 months. Median OS of 15.5 and 7.5 months were observed from the start of 1st line therapy and 2nd line treatment, respectively. No unexpected toxicities occurred. Presence of KRAS mutations was associated with significantly worse median PFS to D+R (2.8 vs. 4.5 months in wild-type cases; P=0.021) and was an independent predictor of inferior PFS in multivariate analysis., Conclusions: D+R is an effective and safe 2nd line treatment after failure of 1st line CTx+ICI irrespective of NSCLC histology. However, patients with a KRAS mutation did not benefit from D+R in terms of PFS and will require further investigations., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tlcr-21-197). Albrecht Stenzinger serves as an unpaid editorial board member of Translational Lung Cancer Research from Sep 2019 to Sep 2021. The following authors received honoraria for lectures, presentation, speakers bureaus, manuscript writing or educational events: WMB from AstraZeneca, Boehringer, Novartis, MSD, BMS, Roche and Lilly; MR from Amgen, AstraZeneca, BMS, Boehringer, Lilly, Minde, Merck, MSD, Novartis, Pfizer and Roche; AR from AbbVIe, AstraZeneca, BMS, Boehringer, Lilly, MSD, Novartis, Pfizer and Roche; CW from Boehringer, Lilly, MSD, Roche, AstraZeneca, BMS, Sanofi Aventis and Takeda; GHW from Boehringer, Lilly, MSD, Roche, AstraZeneca, BMS, Sanofi Aventis, Takeda, Glaxo and Berlin Chemie; PC from Roche, Takeda, AstraZeneca and Novartis; AS from Aignostics, Bayer, Thermo Fisher, Illumina, AstraZeneca, Novartis, Pfizer, Roche, Seattle Genetics, MSD, BMS, Takeda and Lilly; AT from GSK, Novartis, Amgen, BMS, MSD, Lilly, Pfizer, Boehringer, Roche, Takeda and Celgene; JHF from AstraZeneca, Boehringer, Novartis, MSD, BMS and Roche. The following authors received support for attending meetings and/or travel: WMB from Boehringer, AstraZeneca and Roche; CW from Boehringer, MSD, Roche, AstraZeneca and BMS; GW from Boehringer, MSD, Roche, AstraZeneca and Berlin Chemie; PC from AstraZeneca, Takeda, Novartis and Lilly; AT from GSK, Novartis, Amgen, MSD, BMS, Lilly, Pfizer, Boehringer, Roche, Takeda and Celgene; JHF from Boehringer and AstraZeneca. The following authors participated on a data safety monitoring board or an advisory board: WMB on AstraZeneca, Boehringer, Novartis, MSD, Lilly, BMS and Roche; JK on Roche, Boehringer, BMS, Merck, Amgen, Takeda and Lilly (all outside the submitted work and all without receiving any personal fees; CW on Boehringer, MSD, Roche, AstraZeneca and MBS; GHW on Boehringer, MSD, Roche, AstraZeneca and BMS; PC on Pfizer, Chugai, Boehringer and Roche; AT on GSK, Novartis, Amgen, MSD, BMS, Lilly, Pfizer, Boehringer, Roche, Takeda, Celgene and AIO Leadership Group; PH on Lilly, MSD, BMS, AstraZeneca, Takeda, Roche, Boehringer and Pfizer; JHF on AstraZenca. The following authors receipt equipment, materials, drugs, medical writing, gifts or other services: WMB from Boehringer (for medical writing); JHF from Novartis (for medical writing); the following authors received consulting fees: AR from AbbVie, AstraZeneca, BMS, Boehringer, Lilly, MSD, Novartis, Pfizer and Roche. The following authors received grants or contracts form any entity: PC from Roche, Takeda, AstraZeneca and Novartis (all research grants to the institution; AT from AstraZeneca (research grant). The other authors have no conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)
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- 2021
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44. Clinical outcome, risk assessment, and seasonal variation in hospitalized COVID-19 patients-Results from the CORONA Germany study.
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Gessler N, Gunawardene MA, Wohlmuth P, Arnold D, Behr J, Gloeckner C, Herrlinger K, Hoelting T, Pape UF, Schreiber R, Stang A, Wesseler C, Willems S, Arms C, and Herborn CU
- Subjects
- Aged, Aged, 80 and over, COVID-19 epidemiology, COVID-19 mortality, Female, Geography, Germany epidemiology, Hospital Mortality, Humans, Male, Middle Aged, Outcome Assessment, Health Care methods, Pandemics, Prospective Studies, Risk Assessment methods, Risk Factors, SARS-CoV-2 physiology, Severity of Illness Index, COVID-19 prevention & control, Hospitalization statistics & numerical data, Outcome Assessment, Health Care statistics & numerical data, Risk Assessment statistics & numerical data, SARS-CoV-2 isolation & purification, Seasons
- Abstract
Background: After one year of the pandemic and hints of seasonal patterns, temporal variations of in-hospital mortality in COVID-19 are widely unknown. Additionally, heterogeneous data regarding clinical indicators predicting disease severity has been published. However, there is a need for a risk stratification model integrating the effects on disease severity and mortality to support clinical decision-making., Methods: We conducted a multicenter, observational, prospective, epidemiological cohort study at 45 hospitals in Germany. Until 1 January 2021, all hospitalized SARS CoV-2 positive patients were included. A comprehensive data set was collected in a cohort of seven hospitals. The primary objective was disease severity and prediction of mild, severe, and fatal cases. Ancillary analyses included a temporal analysis of all hospitalized COVID-19 patients for the entire year 2020., Findings: A total of 4704 COVID-19 patients were hospitalized with a mortality rate of 19% (890/4704). Rates of mortality, need for ventilation, pneumonia, and respiratory insufficiency showed temporal variations, whereas age had a strong influence on the course of mortality. In cohort conducting analyses, prognostic factors for fatal/severe disease were: age (odds ratio (OR) 1.704, CI:[1.221-2.377]), respiratory rate (OR 1.688, CI:[1.222-2.333]), lactate dehydrogenase (LDH) (OR 1.312, CI:[1.015-1.695]), C-reactive protein (CRP) (OR 2.132, CI:[1.533-2.965]), and creatinine values (OR 2.573, CI:[1.593-4.154]., Conclusions: Age, respiratory rate, LDH, CRP, and creatinine at baseline are associated with all cause death, and need for ventilation/ICU treatment in a nationwide series of COVID 19 hospitalized patients. Especially age plays an important prognostic role. In-hospital mortality showed temporal variation during the year 2020, influenced by age., Trial Registration Number: NCT04659187., Competing Interests: The authors have declared that no competing interests exist that could be perceived to bias this work. The commercial affiliation does not alter our adherence to PLOS ONE policies on sharing data and materials. SW reports grants and personal fees from Abbott and personal feels from Abbott, Boston Scientific, Boehringer Ingelheim, Bristol Myers Squibb, Bayer Vital, Acutus, and Daiichi Sankyo, outside the submitted work.
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- 2021
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45. A Randomized Phase III Study of Abemaciclib Versus Erlotinib in Patients with Stage IV Non-small Cell Lung Cancer With a Detectable KRAS Mutation Who Failed Prior Platinum-Based Therapy: JUNIPER.
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Goldman JW, Mazieres J, Barlesi F, Dragnev KH, Koczywas M, Göskel T, Cortot AB, Girard N, Wesseler C, Bischoff H, Nadal E, Park K, Lu S, Taus A, Cobo M, Estrem ST, Wijayawardana SR, Turner K, Oakley GJ 3rd, Hurt KC, Chiang AY, Hossain AM, John WJ, and Paz-Ares L
- Abstract
Introduction: JUNIPER compared the efficacy and safety of abemaciclib, a selective cyclin-dependent kinase 4 and 6 inhibitor, with erlotinib in patients with non-small cell lung cancer (NSCLC) harboring a Kirsten rat sarcoma ( KRAS ) mutation., Methods: JUNIPER was a Phase III, multicenter, randomized, open-label trial of abemaciclib versus erlotinib in patients with stage IV NSCLC and a detectable mutation in codons 12 or 13 of the KRAS oncogene, who progressed after platinum-based chemotherapy and 1 additional therapy (could include immune checkpoint inhibitor therapy). Randomized patients (3:2) received either 200 mg abemaciclib twice daily or 150 mg erlotinib once daily with best supportive care until disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS); secondary endpoints included overall response rate (ORR), progression-free survival (PFS), and safety., Results: Between December 2014 and April 2017, 453 patients were randomly assigned to receive abemaciclib (N = 270) or erlotinib (N = 183). Median OS was 7.4 months (95% confidence interval [CI]: 6.5, 8.8) with abemaciclib and 7.8 months (95% CI: 6.4, 9.5) with erlotinib (hazard ratio [HR] = 0.968 [95% CI: 0.768, 1.219]; p = .77). Median PFS was 3.6 months (95% CI: 2.8, 3.8) with abemaciclib and 1.9 months (95% CI: 1.9, 2.0) with erlotinib (HR = 0.583 [95% CI: 0.470, 0.723]; p <.000001). ORR was 8.9% and 2.7% (p = .010), and the disease control rate was 54.4% and 31.7% (p <.001) with abemaciclib and erlotinib, respectively. Safety results reflected the known safety profiles of abemaciclib and erlotinib., Conclusions: In this study, the primary endpoint of OS was not met; PFS and ORR were improved with manageable toxicity in the abemaciclib arm. The increases in response rates and PFS support further investigation of abemaciclib in other NSCLC subpopulations or in combination with other agents., Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02152631., (Copyright © 2020 Goldman, Mazieres, Barlesi, Dragnev, Koczywas, Göskel, Cortot, Girard, Wesseler, Bischoff, Nadal, Park, Lu, Taus, Cobo, Estrem, Wijayawardana, Turner, Oakley, Hurt, Chiang, Hossain, John and Paz-Ares.)
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- 2020
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46. Efficacy of Docetaxel Plus Ramucirumab as Palliative Third-Line Therapy Following Second-Line Immune-Checkpoint-Inhibitor Treatment in Patients With Non-Small-Cell Lung Cancer Stage IV.
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Brueckl WM, Reck M, Rittmeyer A, Kollmeier J, Wesseler C, Wiest GH, Christopoulos P, Tufman A, Hoffknecht P, Ulm B, Reich F, Ficker JH, and Laack E
- Abstract
Background: Antiangiogenic agents have been shown to stimulate the immune system and cause synergistic effects with chemotherapy. Effects might be even stronger after immune-checkpoint-inhibitor (ICI) therapy. The purpose of this analysis was to evaluate the efficacy of ramucirumab plus docetaxel (R + D) as third-line treatment after failure of a first-line platinum-based chemotherapy and a second-line ICI treatment in patients with non-small-cell lung cancer (NSCLC) stage IV., Methods: Retrospective data were collected from 9 German thoracic oncology centers. Only patients who had received at least 1 cycle of third-line R + D were included. The numbers of cycles, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were investigated., Results: Sixty-seven patients met the criteria for inclusion. Third-line treatment with R + D achieved an ORR of 36% and a disease control rate (DCR) of 69%. Median PFS for third-line therapy was 6.8 months with a duration of response (DOR) of 10.2 months. A median OS of 29 months was observed from the start of first-line therapy with a median OS of 11.0 months from the start of third-line treatment. No unexpected toxicities occurred., Conclusion: R + D is a highly effective and safe third-line treatment after failure of second-line programmed cell death protein 1/programmed cell death-ligand 1 (PD1/PD-L1)-derived ICI therapy irrespective of NSCLC histology. As there may be synergistic effects of second- and third-line treatments, this sequence is a very suitable option for patients not treated with first-line ICI. In addition, R + D should continue to be investigated as a second-line treatment option after failure of chemotherapy plus ICI in the palliative first-line treatment., Competing Interests: Declaration of Conflicting Interest:The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: W.M.B. and J.H.F. have received honoraria for consulting from Astra Zeneca, BMS, Boehringer Ingelheim, Celgene, Lilly, MSD, Pfizer, and Roche Pharma. P.C. reports consulting honoraria from Astra Zeneca, Boehringer Ingelheim, Chugai, Lilly, Novartis, Pfizer, Roche, and Takeda. P.H. has received honoraria for consulting from Boehringer Ingelheim, Pfizer, Takeda, Roche Pharma, Lilly, BMS, MSD, AstraZeneca, and Abbvie. F.R. has received honoraria for consulting from Astra Zeneca, Chugai Pharma, and Roche Pharma. C.W. and G.H.W. have received honoraria for consulting from Astra Zeneca, BMS, Boehringer Ingelheim, Lilly, MSD, Pfizer, and Roche Pharma. The other authors reported no conflict of interest., (© The Author(s) 2020.)
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- 2020
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47. Integration of Tumor Mutation Burden and PD-L1 Testing in Routine Laboratory Diagnostics in Non-Small Cell Lung Cancer.
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Schatz S, Falk M, Jóri B, Ramdani HO, Schmidt S, Willing EM, Menon R, Groen HJM, Diehl L, Kröger M, Wesseler C, Griesinger F, Hoffknecht P, Tiemann M, and Heukamp LC
- Abstract
In recent years, Non-small cell lung cancer (NSCLC) has evolved into a prime example for precision oncology with multiple FDA-approved "precision" drugs. For the majority of NSCLC lacking targetable genetic alterations, immune checkpoint inhibition (ICI) has become standard of care in first-line treatment or beyond. PD-L1 tumor expression represents the only approved predictive biomarker for PD-L1/PD-1 checkpoint inhibition by therapeutic antibodies. Since PD-L1-negative or low-expressing tumors may also respond to ICI, additional factors are likely to contribute in addition to PD-L1 expression. Tumor mutation burden (TMB) has emerged as a potential candidate; however, it is the most complex biomarker so far and might represent a challenge for routine diagnostics. We therefore established a hybrid capture (HC) next-generation sequencing (NGS) assay that covers all oncogenic driver alterations as well as TMB and validated TMB values by correlation with the assay (F1CDx) used for the CheckMate 227 study. Results of the first consecutive 417 patients analyzed in a routine clinical setting are presented. Data show that fast reliable comprehensive diagnostics including TMB and targetable alterations are obtained with a short turn-around time. Thus, even complex biomarkers can easily be implemented in routine practice to optimize treatment decisions for advanced NSCLC.
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- 2020
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