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Brain metastases, treatment patterns and outcomes in ROS1-positive NSCLC patients from US oncology community centers
abstracts
Annals of Oncology
1551P
Brain metastases, treatment patterns and outcomes in ROS1-positive NSCLC patients from US oncology community centers
M.G. Krebs1, L. Perez2, A. Surinach3, R.C. Doebele4, R. Martina5, M. Martinec2, T. Riehl6, N.J. Meropol7, W. Wong6, G. Crane8 1 Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester and The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK, 2F. Hoffmann-La Roche Ltd, Basel, Switzerland, 3 Genesis Research, Hoboken, NJ, USA, 4Thoracic Oncology Research Initiative, University of Colorado, Aurora, CO, USA, 5Biostatistics, University of Liverpool, Liverpool, UK, 6 Genentech, South San Francisco, CA, USA, 7Flatiron Health, New York, NY, USA, 8 F. Hoffmann-La Roche Ltd, Welwyn Garden City, UK Background: As new targeted therapies with CNS penetration and activity for nonsmall cell lung cancer (NSCLC) with ROS1 gene fusions (ROS1þ) emerge, there is a need to characterize the disease course of patients (pts) receiving current treatment, especially in relation to CNS metastases (met). Methods: We evaluated an anonymized cohort of ROS1þ NSCLC pts from the Flatiron Health electronic health record (EHR)-derived database of US cancer centers (2011–2018). Descriptive statistics were used for clinical and treatment pattern characterization. Kaplan-Meier curves estimated median overall survival (OS), real-world progression-free survival (rwPFS, using physician documentation in the EHR) and rwPFS in the CNS, from 1st-line treatment (1L) after diagnosis of advanced/metastatic NSCLC (aNSCLC Dx). Due to low numbers of pts in some groups, 95% CI are not reported. Results: We identified 129 ROS1þ aNSCLC pts who received 1L treatment including crizotinib (n ¼ 52, 40.3%), chemotherapy (n ¼ 34, 26.4%), combination systemic therapy (n ¼ 25, 19.4%), clinical study drug (n ¼ 4, 3.1%), or no treatment (n ¼ 14, 10.9%). For 1L crizotinib (the only approved therapy for ROS1þ NSCLC) after aNSCLC Dx median rwPFS: 8.6 m (95% CI: 6.2–12.1); OS: 19.9 m (95% CI: 15.1–NR). For pts receiving other 1L drugs median rwPFS: 5.9 m (95% CI: 4.1–7.2); OS: 18.1 m (95% CI: 12.9–34.6). There were 24 pts (18%) with CNS met at diagnosis and 20 pts (19%) at follow-up. Most pts with CNS met at or after diagnosis received surgery/ radiotherapy (37/44, 84.1%). For CNS met pts who received 1L crizotinib after local treatment (6/11), median rwPFS: 8.0 m; OS: 27 m. From 1L crizotinib, pts with CNS met at follow-up only (10/21 pts with CNS mets who received 1L crizotinib), median rwPFS: 7.2 m; rwPFS-CNS: 9.1 m; OS: 15.1 m. For pts with no CNS mets anytime median rwPFS: 10.0 m; OS: 21.5 m from 1L crizotinib (34/55 pts). Conclusions: In the US, ROS1þ NSCLC pts receive various 1L treatments after aNSCLC Dx. CNS was a site of metastasis in 44/129 ROS1þ NSCLC pts. Surgery/radiotherapy for CNS mets prior to systemic therapy appeared to result in favorable outcomes, however conclusions on the natural history of cancers with rare mutations rely on very small patient numbers. Editorial acknowledgement: Laura Vergoz and Charlotte Kennerley, PhD of Gardiner-Caldwell Communications, funded by F. Hoffmann-La Roche. Legal entity responsible for the study: F. Hoffmann-La Roche. Funding: F. Hoffmann-La Roche. Disclosure: M.G. Krebs: Advisory / Consultancy, Officer / Board of Directors: Roche, Achilles Therapeutics, Octimet, Janssen; Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca, Bayer, BerGenBio, Blueprint, Carrick, Immutep, Incyte, Janssen, Merck, Octimet, Roche; Travel / Accommodation / Expenses: AstraZeneca, BerGenBio. L. Perez: Research grant / Funding (institution), Shareholder / Stockholder / Stock options: Roche. A. Surinach: Full / Part-time employment: Genesis Research. R.C. Doebele: Shareholder / Stockholder / Stock options: Rain Therapeutics; Advisory / Consultancy: Chair of Scientific Advisory Board for Rain Therapeutics; Honoraria (self): Guardant; Advisory / Consultancy: Pfizer, Trovagene, Ariad, Takeda, AstraZeneca, Genentech/Roche, Ignyta, Loxo, Rain Therapeutics; Research grant / Funding (self), Research grant / Funding (institution): Ignyta, Loxo, Mirati; Licensing / Royalties: Molecular, Rain Therapeutics, GVKbio, Chugai, Loxo, Ignyta, Genentech, Ariad, Foundation Medicine, Black Diamond. M. Martinec: Research grant / Funding (self), Shareholder / Stockholder / Stock options, Full / Part-time employment: F. Hoffmann-La Roche Ltd. T. Riehl: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche/Genentech. N.J. Meropol: Shareholder / Stockholder / Stock options: Roche; Shareholder / Stockholder / Stock options, Full / Part-time employment: Flatiron Health, Inc. W. Wong: Shareholder / Stockholder / Stock options: Roche; Full / Part-time employment: Genentech. G. Crane: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. All other authors have declared no conflicts of interest.
Volume 30 | Supplement 5 | October 2019
1552P
Patients with metastatic non-small cell lung cancer and targetable molecular alterations in Germany. Treatment and first outcome data from the prospective German Registry Platform CRISP (AIO-TRK-0315)
F. Griesinger1, W.E.E. Eberhardt2, A. Nusch3, M. Reiser4, M-O. Zahn5, N.W. Marschner6, M. J€anicke7, A. Fleitz7, L. Spring7, J. Sahlmann8, A. Karatas9, A. Hipper9, W. Weichert10, C. Waller11, M. Reck12, P. Christopoulos13, M. Sebastian14, M. Thomas15 1 Oncology, Pius Hospital, University of Oldenburg, Oldenburg, Germany, 2Department of Medical Oncology, University Hospital Essen, Westdeutsches Tumorzentrum, Essen, amatologie und internistische Onkologie, Ratingen, Germany, 3Onkologie, Praxis fu¨r H€ amatologie, PIOH (Ko¨ln Zentrum), Germany, 4Praxis Internistischer Onkologie und H€ Cologne, Germany, 5Oncology & Haematology, MVZ Onkologische Kooperation Harz, 6 are Onkologie & H€ amatologie, Goslar, Germany, Oncology, Praxis fu¨r interdisziplin€ Freiburg, Germany, 7Clinical Epidemiology and Health Economics, IOMEDICO, Freiburg, 8 Germany, Department of Data Management, Statistics and Medical Informatics, IOMEDICO AG, Freiburg Im Breisgau, Germany, 9AIO, Studien gGmbH, Berlin, Germany, 10 Institute of Pathology, Technische Universit€ at Mu¨nchen, Munich, Germany, 11Klinik fu¨r Innere Medizin, H€ amatologie, Onkologie und Stammzelltransplantation, Universit€ atsklinikum Freiburg, Freiburg Im Breisgau, Germany, 12Thoracic Oncology, Lung Clinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, Grosshansdorf, Germany, 13Translational Lung Research Center Heidelberg (TLRC-H), Thoraxklinik Heidelberg, Heidelberg, Germany, 14Department of Hematology/ Medical Oncology, Universit€ atsklinikum Frankfurt, Frankfurt am Main, Germany, 15 Medical Oncology, Thoraxklinik Heidelberg, Heidelberg, Germany Background: Guidelines for metastatic non-small cell lung cancer recommend stratified treatment by biomarker test results. We used CRISP to evaluate treatment and outcome of patients (pts) with targetable molecular alterations. Methods: Currently 163 sites in Germany have recruited >3700 pts at start of 1st-line who will be followed until death or end of project. Data from 2204 pts recruited by 133 sites from 12/2015 to 06/2018 was analyzed. Progression-free survival (PFS) was determined in pts observed 1 year (recruited <06/2017 (n ¼ 906), outcome sample (ous)). Results: 94%/65% of 1732/472 pts with non-squamous/squamous tumors were tested for any biomarker. In 2018 test rate was 96%/75% and 49%/33% were tested for all biomarkers (EGFR, ALK, ROS1, BRAF) with approved targeted therapies (aTT). An alteration in EGFR, ALK, ROS1 or BRAF was detected in 9%, 3%, 2%, and 2% of pts, respectively. Details on the type of alteration will be presented. Of pts with druggable EGFR mutation (EGFRþ pts, n ¼ 149) 78% received EGFR-aTT in 1st-line. In 2nd-line, 20% received EGFR-aTT, 15% something else, 11% died prior to 2nd-line, 54% were still in 1st-line. Median PFS of EGFRþ pts was 7.1 months (n ¼ 67, 61% events, 95%-CI 5.2-10.1), in total 46% (n ¼ 31) of pts had died (ous). Of pts with druggable ALK alteration (n ¼ 55), 47% received ALK-aTT in 1st-line. In 2nd-line, 22% received ALK-aTT, 11% something else, 13% died prior to 2nd-line, 54% were still in 1st-line. In the ous (n ¼ 29), 55% (n ¼ 16) of tumors had already progressed, in total 24% (n ¼ 7) of pts had died. All 6 pts with druggable ROS1 alteration received chemotherapy as 1st-line, while 6 of the 9 pts with druggable BRAF mutation and start of treatment in 2017/18 received a BRAF-ATT in 1st-line. Conclusions: CRISP presents current real life data from Germany. Pts are frequently tested for molecular alterations. While EGFR-aTT is well established as 1st-line and first data are promising for BRAF-aTT, pts with ALK/ROS alteration do not seem to be routinely treated with 1st-line aTT, reasons are not yet clear and will be further evaluated. Outcome of pts will be further analyzed after longer follow-up. Clinical trial identification: NCT02622581. Legal entity responsible for the study: AIO-Studien-gGmbH. Funding: AstraZeneca GmbH, Boehringer Ingelheim Pharma GmbH & Co. KG, Bristol-Myers Squibb GmbH & Co. KGaA, Celgene GmbH, MSD Sharp & Dohme GmbH, Lilly Deutschland GmbH, Novartis Pharma GmbH, Pfizer Pharma GmbH, Roche Pharma AG, and Takeda Pharma Vertriebs GmbH & Co. KG. Disclosure: F. Griesinger: Honoraria (institution), Advisory / Consultancy: Ariad; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myer-Squibb; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Celgene; Honoraria (institution), Advisory / Consultancy: Clovis; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Merck-Sharp-Dome; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Roche. N.W. Marschner: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): MSD Sharp & Dohme; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Leadership role, Shareholder / Stockholder / Stock options, Officer / Board of Directors: iOMEDICO. M. J€anicke: Leadership role, Full / Part-time employment: iOMEDICO. A. Fleitz: Full / Part-time employment: iOMEDICO. L. Spring: Full / Part-time employment: iOMEDICO. J. Sahlmann: Leadership role, Full / Part-time employment: iOMEDICO. A. Karatas: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): MSD Sharp & Dohme; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Roche. A. Hipper: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding
doi:10.1093/annonc/mdz260 | v639
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz260.073/5578180 by guest on 24 October 2019
Results: Allele-specific PCR detected MET exon 14 skipping in 35/1415 (2.5%) EGFR mutation–negative LCs. There was a highly pronounced association with the elderly age of the patients (median age 69 years as compared to 62 years in EGFR/ALK/MET mutation-negative cases; p ¼ 1.821e-06). 34/35 (97%) LCs with MET exon 14 skipping mutations showed preferential expression of the affected MET allele, while the wildtype transcript was almost undetectable in these tumors. In addition, we identified a subset of MET wild-type LCs, which produced normal MET transcript but also expressed residual amounts of MET exon 14D RNA message, probably due to alternative splicing. Conclusions: The mere detection of MET exon 14D signal by allele-specific PCR does not warrant the presence of corresponding clonal MET mutation. Comparison of expression of MET exon 14D and wild-type alleles is essential for reliable identification of tumors carrying drug-sensitizing MET lesions. Legal entity responsible for the study: The authors. Funding: Russian Science Foundation (grant 17-75-30027). Disclosure: All authors have declared no conflicts of interest.
Annals of Oncology
1551P
Brain metastases, treatment patterns and outcomes in ROS1-positive NSCLC patients from US oncology community centers
M.G. Krebs1, L. Perez2, A. Surinach3, R.C. Doebele4, R. Martina5, M. Martinec2, T. Riehl6, N.J. Meropol7, W. Wong6, G. Crane8 1 Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester and The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK, 2F. Hoffmann-La Roche Ltd, Basel, Switzerland, 3 Genesis Research, Hoboken, NJ, USA, 4Thoracic Oncology Research Initiative, University of Colorado, Aurora, CO, USA, 5Biostatistics, University of Liverpool, Liverpool, UK, 6 Genentech, South San Francisco, CA, USA, 7Flatiron Health, New York, NY, USA, 8 F. Hoffmann-La Roche Ltd, Welwyn Garden City, UK Background: As new targeted therapies with CNS penetration and activity for nonsmall cell lung cancer (NSCLC) with ROS1 gene fusions (ROS1þ) emerge, there is a need to characterize the disease course of patients (pts) receiving current treatment, especially in relation to CNS metastases (met). Methods: We evaluated an anonymized cohort of ROS1þ NSCLC pts from the Flatiron Health electronic health record (EHR)-derived database of US cancer centers (2011–2018). Descriptive statistics were used for clinical and treatment pattern characterization. Kaplan-Meier curves estimated median overall survival (OS), real-world progression-free survival (rwPFS, using physician documentation in the EHR) and rwPFS in the CNS, from 1st-line treatment (1L) after diagnosis of advanced/metastatic NSCLC (aNSCLC Dx). Due to low numbers of pts in some groups, 95% CI are not reported. Results: We identified 129 ROS1þ aNSCLC pts who received 1L treatment including crizotinib (n ¼ 52, 40.3%), chemotherapy (n ¼ 34, 26.4%), combination systemic therapy (n ¼ 25, 19.4%), clinical study drug (n ¼ 4, 3.1%), or no treatment (n ¼ 14, 10.9%). For 1L crizotinib (the only approved therapy for ROS1þ NSCLC) after aNSCLC Dx median rwPFS: 8.6 m (95% CI: 6.2–12.1); OS: 19.9 m (95% CI: 15.1–NR). For pts receiving other 1L drugs median rwPFS: 5.9 m (95% CI: 4.1–7.2); OS: 18.1 m (95% CI: 12.9–34.6). There were 24 pts (18%) with CNS met at diagnosis and 20 pts (19%) at follow-up. Most pts with CNS met at or after diagnosis received surgery/ radiotherapy (37/44, 84.1%). For CNS met pts who received 1L crizotinib after local treatment (6/11), median rwPFS: 8.0 m; OS: 27 m. From 1L crizotinib, pts with CNS met at follow-up only (10/21 pts with CNS mets who received 1L crizotinib), median rwPFS: 7.2 m; rwPFS-CNS: 9.1 m; OS: 15.1 m. For pts with no CNS mets anytime median rwPFS: 10.0 m; OS: 21.5 m from 1L crizotinib (34/55 pts). Conclusions: In the US, ROS1þ NSCLC pts receive various 1L treatments after aNSCLC Dx. CNS was a site of metastasis in 44/129 ROS1þ NSCLC pts. Surgery/radiotherapy for CNS mets prior to systemic therapy appeared to result in favorable outcomes, however conclusions on the natural history of cancers with rare mutations rely on very small patient numbers. Editorial acknowledgement: Laura Vergoz and Charlotte Kennerley, PhD of Gardiner-Caldwell Communications, funded by F. Hoffmann-La Roche. Legal entity responsible for the study: F. Hoffmann-La Roche. Funding: F. Hoffmann-La Roche. Disclosure: M.G. Krebs: Advisory / Consultancy, Officer / Board of Directors: Roche, Achilles Therapeutics, Octimet, Janssen; Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca, Bayer, BerGenBio, Blueprint, Carrick, Immutep, Incyte, Janssen, Merck, Octimet, Roche; Travel / Accommodation / Expenses: AstraZeneca, BerGenBio. L. Perez: Research grant / Funding (institution), Shareholder / Stockholder / Stock options: Roche. A. Surinach: Full / Part-time employment: Genesis Research. R.C. Doebele: Shareholder / Stockholder / Stock options: Rain Therapeutics; Advisory / Consultancy: Chair of Scientific Advisory Board for Rain Therapeutics; Honoraria (self): Guardant; Advisory / Consultancy: Pfizer, Trovagene, Ariad, Takeda, AstraZeneca, Genentech/Roche, Ignyta, Loxo, Rain Therapeutics; Research grant / Funding (self), Research grant / Funding (institution): Ignyta, Loxo, Mirati; Licensing / Royalties: Molecular, Rain Therapeutics, GVKbio, Chugai, Loxo, Ignyta, Genentech, Ariad, Foundation Medicine, Black Diamond. M. Martinec: Research grant / Funding (self), Shareholder / Stockholder / Stock options, Full / Part-time employment: F. Hoffmann-La Roche Ltd. T. Riehl: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche/Genentech. N.J. Meropol: Shareholder / Stockholder / Stock options: Roche; Shareholder / Stockholder / Stock options, Full / Part-time employment: Flatiron Health, Inc. W. Wong: Shareholder / Stockholder / Stock options: Roche; Full / Part-time employment: Genentech. G. Crane: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. All other authors have declared no conflicts of interest.
Volume 30 | Supplement 5 | October 2019
1552P
Patients with metastatic non-small cell lung cancer and targetable molecular alterations in Germany. Treatment and first outcome data from the prospective German Registry Platform CRISP (AIO-TRK-0315)
F. Griesinger1, W.E.E. Eberhardt2, A. Nusch3, M. Reiser4, M-O. Zahn5, N.W. Marschner6, M. J€anicke7, A. Fleitz7, L. Spring7, J. Sahlmann8, A. Karatas9, A. Hipper9, W. Weichert10, C. Waller11, M. Reck12, P. Christopoulos13, M. Sebastian14, M. Thomas15 1 Oncology, Pius Hospital, University of Oldenburg, Oldenburg, Germany, 2Department of Medical Oncology, University Hospital Essen, Westdeutsches Tumorzentrum, Essen, amatologie und internistische Onkologie, Ratingen, Germany, 3Onkologie, Praxis fu¨r H€ amatologie, PIOH (Ko¨ln Zentrum), Germany, 4Praxis Internistischer Onkologie und H€ Cologne, Germany, 5Oncology & Haematology, MVZ Onkologische Kooperation Harz, 6 are Onkologie & H€ amatologie, Goslar, Germany, Oncology, Praxis fu¨r interdisziplin€ Freiburg, Germany, 7Clinical Epidemiology and Health Economics, IOMEDICO, Freiburg, 8 Germany, Department of Data Management, Statistics and Medical Informatics, IOMEDICO AG, Freiburg Im Breisgau, Germany, 9AIO, Studien gGmbH, Berlin, Germany, 10 Institute of Pathology, Technische Universit€ at Mu¨nchen, Munich, Germany, 11Klinik fu¨r Innere Medizin, H€ amatologie, Onkologie und Stammzelltransplantation, Universit€ atsklinikum Freiburg, Freiburg Im Breisgau, Germany, 12Thoracic Oncology, Lung Clinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, Grosshansdorf, Germany, 13Translational Lung Research Center Heidelberg (TLRC-H), Thoraxklinik Heidelberg, Heidelberg, Germany, 14Department of Hematology/ Medical Oncology, Universit€ atsklinikum Frankfurt, Frankfurt am Main, Germany, 15 Medical Oncology, Thoraxklinik Heidelberg, Heidelberg, Germany Background: Guidelines for metastatic non-small cell lung cancer recommend stratified treatment by biomarker test results. We used CRISP to evaluate treatment and outcome of patients (pts) with targetable molecular alterations. Methods: Currently 163 sites in Germany have recruited >3700 pts at start of 1st-line who will be followed until death or end of project. Data from 2204 pts recruited by 133 sites from 12/2015 to 06/2018 was analyzed. Progression-free survival (PFS) was determined in pts observed 1 year (recruited <06/2017 (n ¼ 906), outcome sample (ous)). Results: 94%/65% of 1732/472 pts with non-squamous/squamous tumors were tested for any biomarker. In 2018 test rate was 96%/75% and 49%/33% were tested for all biomarkers (EGFR, ALK, ROS1, BRAF) with approved targeted therapies (aTT). An alteration in EGFR, ALK, ROS1 or BRAF was detected in 9%, 3%, 2%, and 2% of pts, respectively. Details on the type of alteration will be presented. Of pts with druggable EGFR mutation (EGFRþ pts, n ¼ 149) 78% received EGFR-aTT in 1st-line. In 2nd-line, 20% received EGFR-aTT, 15% something else, 11% died prior to 2nd-line, 54% were still in 1st-line. Median PFS of EGFRþ pts was 7.1 months (n ¼ 67, 61% events, 95%-CI 5.2-10.1), in total 46% (n ¼ 31) of pts had died (ous). Of pts with druggable ALK alteration (n ¼ 55), 47% received ALK-aTT in 1st-line. In 2nd-line, 22% received ALK-aTT, 11% something else, 13% died prior to 2nd-line, 54% were still in 1st-line. In the ous (n ¼ 29), 55% (n ¼ 16) of tumors had already progressed, in total 24% (n ¼ 7) of pts had died. All 6 pts with druggable ROS1 alteration received chemotherapy as 1st-line, while 6 of the 9 pts with druggable BRAF mutation and start of treatment in 2017/18 received a BRAF-ATT in 1st-line. Conclusions: CRISP presents current real life data from Germany. Pts are frequently tested for molecular alterations. While EGFR-aTT is well established as 1st-line and first data are promising for BRAF-aTT, pts with ALK/ROS alteration do not seem to be routinely treated with 1st-line aTT, reasons are not yet clear and will be further evaluated. Outcome of pts will be further analyzed after longer follow-up. Clinical trial identification: NCT02622581. Legal entity responsible for the study: AIO-Studien-gGmbH. Funding: AstraZeneca GmbH, Boehringer Ingelheim Pharma GmbH & Co. KG, Bristol-Myers Squibb GmbH & Co. KGaA, Celgene GmbH, MSD Sharp & Dohme GmbH, Lilly Deutschland GmbH, Novartis Pharma GmbH, Pfizer Pharma GmbH, Roche Pharma AG, and Takeda Pharma Vertriebs GmbH & Co. KG. Disclosure: F. Griesinger: Honoraria (institution), Advisory / Consultancy: Ariad; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myer-Squibb; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Celgene; Honoraria (institution), Advisory / Consultancy: Clovis; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Merck-Sharp-Dome; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Roche. N.W. Marschner: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): MSD Sharp & Dohme; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Leadership role, Shareholder / Stockholder / Stock options, Officer / Board of Directors: iOMEDICO. M. J€anicke: Leadership role, Full / Part-time employment: iOMEDICO. A. Fleitz: Full / Part-time employment: iOMEDICO. L. Spring: Full / Part-time employment: iOMEDICO. J. Sahlmann: Leadership role, Full / Part-time employment: iOMEDICO. A. Karatas: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): MSD Sharp & Dohme; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Roche. A. Hipper: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding
doi:10.1093/annonc/mdz260 | v639
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz260.073/5578180 by guest on 24 October 2019
Results: Allele-specific PCR detected MET exon 14 skipping in 35/1415 (2.5%) EGFR mutation–negative LCs. There was a highly pronounced association with the elderly age of the patients (median age 69 years as compared to 62 years in EGFR/ALK/MET mutation-negative cases; p ¼ 1.821e-06). 34/35 (97%) LCs with MET exon 14 skipping mutations showed preferential expression of the affected MET allele, while the wildtype transcript was almost undetectable in these tumors. In addition, we identified a subset of MET wild-type LCs, which produced normal MET transcript but also expressed residual amounts of MET exon 14D RNA message, probably due to alternative splicing. Conclusions: The mere detection of MET exon 14D signal by allele-specific PCR does not warrant the presence of corresponding clonal MET mutation. Comparison of expression of MET exon 14D and wild-type alleles is essential for reliable identification of tumors carrying drug-sensitizing MET lesions. Legal entity responsible for the study: The authors. Funding: Russian Science Foundation (grant 17-75-30027). Disclosure: All authors have declared no conflicts of interest.