- Email: [email protected]
Longitudinal circulating tumour DNA (ctDNA) monitoring for early detection of disease progression and resistance in advanced NSCLC in FLAURA
abstracts
Annals of Oncology Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca. D. Planchard: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, MedImmune, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Honoraria (self): AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Research grant / Funding (institution): AstraZeneca, Bristol-Myers Squibb, AbbVie, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, MedImmune, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo; Travel / Accommodation / Expenses: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim , Roche, Merck, Novartis, prIME Oncology, Pfizer. J.F. Vansteenkiste: Research grant / Funding (institution): MSD; Advisory / Consultancy: – Apotex, AstraZeneca, Boehringer Ingelheim, MSD, Novartis, Roche; Speaker Bureau / Expert testimony: – AstraZeneca, BMS, MSD, Roche. J.E. Gray: Honoraria (self): AstraZeneca, Bristol-Myers Squibb, Takeda; Advisory / Consultancy: Bristol-Myers Squibb, Celgene, Takeda; Research grant / Funding (institution): Array, Merck, AstraZeneca, Genentech, Boehringer Ingelheim, Bristol-Myers Squibb. R. Shah: Honoraria (self), Travel / Accommodation / Expenses: Boehringer Ingelheim, Roche, AstraZeneca. P.K. Cheema: Honoraria (self), Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Merck, Takeda, Novartis, Genomic Health, Pfizer. M. Tiseo: Advisory / Consultancy: AstraZeneca, Bristol-Myers Squibb, MSD, Boehringer Ingelheim, Takeda; Research grant / Funding (institution): AstraZeneca, Boehringer Ingelheim. T. John: Advisory / Consultancy: Roche, BristolMyers Squibb, Merck, Ignyta, AstraZeneca, Takeda, Boehringer Ingelheim, Pfizer. R. Hodge: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. Y. Rukazenkov: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. J. Soria: Advisory / Consultancy: AstraZeneca, Astex, Clovis, GSK, GamaMabs, Lilly, MSD, Mission Therapeutics, Merus, Pfizer, PharmaMar, Pierre Fabre, Roche/Genentech, Sanofi, Servier, Symphogen, Takeda; Shareholder / Stockholder / Stock options: AstraZeneca, Gritstone; Full / Parttime employment: AstraZeneca. F. Imamura: Honoraria (self), Research grant / Funding (institution): AstraZeneca. S.S. Ramalingam: Honoraria (self), Advisory / Consultancy: AstraZeneca, Amgen, Bristol-Myers Squibb, Merck, Roche/Genentech, Loxo, Nektar, Tesaro; Research grant / Funding (institution): AstraZeneca, Amgen, Bristol-Myers Squibb, Merck, Tesaro, Advaxis, Takeda.
LBA17
Longitudinal circulating tumour DNA (ctDNA) monitoring for early detection of disease progression and resistance in advanced NSCLC in FLAURA
T. Reungwetwattana1, J. Gray2, A. Markovets3, N. Nogami4, J.S. Lee5, B.C. Cho6, B. Chewaskulyong7, M. Majem8, N. Peled9, K. Vishwanathan10, A. Todd11, Y. Rukazenkov12, M. Johnson13, C. Barrett3, J. Chmielecki3, R. Hartmaier3, S. Ramalingam14 1 Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, 2Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA, 3 Translational Medicines, Research and Early Development, Oncology R&D, AstraZeneca, Boston, MA, USA, 4Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan, 5Department of Medical Oncology, Seoul National University Bundang Hospital, Seoul, Republic of Korea, 6 Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea, 7Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai, Thailand, 8Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, 9Soroka Cancer Center, Ben-Gurion University, Beer Sheva, Israel, 10Clinical Pharmacology and Safety Science, R&D, AstraZeneca, Boston, MA, USA, 11Oncology Biometrics, Oncology R&D, AstraZeneca, Cambridge, UK, 12Oncology R&D, AstraZeneca, Cambridge, UK, 13 Quantitative Clinical Pharmacology, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge, UK, 14Winship Cancer Institute, Emory University, Atlanta, GA, USA Background: In the phase III FLAURA study (NCT02296125), the 3rd-generation EGFR-TKI osimertinib showed superior efficacy to comparator EGFR-TKIs in previously untreated EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC). Here we report results from an exploratory analysis of ctDNA for the early detection of disease progression (PD) in FLAURA. Methods: Treatment-naı¨ve patients (pts) with EGFRm (ex19del/L858R) locally advanced/metastatic NSCLC (n ¼ 556) were randomised 1:1 (osimertinib 80 mg qd: comparator [gefitinib 250 mg qd/erlotinib 150 mg qd]). Plasma samples were collected on Days 1, 8 and 15, then every 21 days for weeks (W) 3–18, then every 6W thereafter. In pts who had a plasma sample on PD and/or discontinuation, ctDNA droplet digital PCR (ddPCR; Biodesix) for EGFRm (ex19del/L858R/T790M) was performed at all available time points and C797S for post-W6 time points. C797S and T790M were the only resistance mutations assayed. ctDNA progression was defined with respect to the nadir ctDNA result and its proximity to the ddPCR detection and quantification limits. Results: The ctDNA progression analysis included 122/556 (22%) pts with valid longitudinal monitoring ddPCR data and RECIST PD by DCO1 (12 June 2017). Across both arms, ctDNA progression preceded or co-occurred with PD in 80/122 (66%) pts with 2.7 months (mo) median lead time; 9.5 mo median progression-free survival (mPFS; n ¼ 80). Acquired C797S or T790M was detected in 57/122 (47%) pts with ctDNA progression (osimertinib 4/50 [8%] C797S, comparator 53/72 [74%] T790M); median time to detection was 16.7 and 8.4 mo for the osimertinib and comparator arms, respectively, mirroring overall mPFS. In pts with ctDNA progression and PD (n ¼ 106), acquired T790M and C797S were detected either at the same time as, or earlier than PD in 41/106 (38%) pts (osimertinib 2/39 [5%], comparator 39/67 [58%]); median lead time was 1.4 mo. Conclusions: ctDNA monitoring may allow for earlier identification of pts who progress on first-line EGFR-TKI therapy and the detection of EGFR-mediated resistance mechanisms in advance of PD in EGFRm NSCLC. Future work aims to explore early detection of non-EGFR-mediated resistance.
Volume 30 | Supplement 9 | November 2019
Clinical trial identification: NCT02296125. Editorial acknowledgement: Donna Tillotson, PhD, of iMed Comms, Macclesfield, UK, an Ashfield Company, part of UDG Healthcare plc, funded by AstraZeneca in accordance with Good Publications Practice (GPP3) guidelines. Legal entity responsible for the study: AstraZeneca. Funding: AstraZeneca. Disclosure: J.E. Gray: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Array; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Takeda. A. Markovets: Shareholder / Stockholder / Stock options, Full / Parttime employment: AstraZeneca. N. Nogami: Honoraria (self): Pfizer Inc., Chugai Pharmaceutical Co. Ltd, Eli Lilly, Taiho Pharmaceutical Co. Ltd., AstraZeneca, Kyowa Hakko Kirin, Ono Pharmaceutical Co. Ltd., Bristol-Myers Squibb, MSD. B.C. Cho: Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Janssen, Yuhan, Ono Pharmaceutical, Dizal Pharma, MSD; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Licensing / Royalties: Champions Oncology; Honoraria (institution), Advisory / Consultancy: Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Pfizer, Eli Lilly, Takeda; Shareholder / Stockholder / Stock options: TheraCanVac Inc. B. Chewaskulyong: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca. M. Majem: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy: Tesaro; Speaker Bureau / Expert testimony: Hellsin; Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pierre Fabre; Speaker Bureau / Expert testimony: Amgen. N. Peled: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Novartis, Pfizer, Roche, Takeda; Advisory / Consultancy: Eli Lilly; Honoraria (self): Foundation Medicine; Shareholder / Stockholder / Stock options: Novellus Dx; Honoraria (self): Guardant360. K. Vishwanathan: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. A. Todd: Full / Part-time employment: AstraZeneca. Y. Rukazenkov: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. M. Johnson: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. C. Barrett: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. J. Chmielecki: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. R. Hartmaier: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca; Shareholder / Stockholder / Stock options, Licensing / Royalties, Nfe2l2 exon 2 ano/or exon 3 loss from work conducted at Foundation Medicine; provisional patent filed: Foundation Medicine. S.S. Ramalingam: Advisory / Consultancy, Research grant / Funding (self): Amgen, AstraZeneca, Bristol-Myers Squibb, Merck; Advisory / Consultancy: AbbVie, Celgene, Genentech, Lilly, Loxo, Takeda; Research grant / Funding (self): Tesaro.
LBA18
Survival and treatment patterns in patients (pts) with locally advanced or metastatic NSCLC treated with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIS): Analysis of US insurance claims databases
R. Soo1, T. Seto2, J.E. Gray3, P. Karimi4, A. Taylor5, W. Sawyer6, E. Thiel7, E. Marchlewicz7, M. Brouillette7 1 Department Haematology-Oncology, National University Hospital, Singapore, 2 Thoracic Oncology, NHO Kyushu Cancer Center, Fukuoka, Japan, 3Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA, 4 Oncology Business Unit, AstraZeneca, Gaithersburg, MD, USA, 5Oncology Business Unit, AstraZeneca, Cambridge, UK, 6Biometrics Oncology, AstraZeneca, Cambridge, UK, 7 Custom Data Analytics, IBM Watson Health, Cambridge, MA, USA Background: Most pts with EGFR mutation-positive (EGFRm) NSCLC develop firstline (1L) EGFR-TKI resistance. Previous analyses of US insurance databases have studied healthcare utilisation and expenditure in pts with EGFRm NSCLC starting first-/second-generation (1G/2G) EGFR-TKIs. We examined treatment patterns and survival rates among pts with locally advanced/metastatic NSCLC, who received 1L 1G/ 2G EGFR-TKIs, in a retrospective analysis of data from the MarketScan Commercial and Medicare Supplemental databases (all US census regions). We also assessed the effect of central nervous system metastases (CNS mets) on survival rates. Methods: Pts 18 yrs with EGFRm NSCLC who received 1L 1G/2G EGFR-TKI were analysed from date of first lung cancer diagnosis (index date) through a variable-length follow-up period. Pts included had 1 pharmacy claim for 1G/2G EGFR-TKI on/ within 60 days post index, and 2 non-diagnostic claims with a diagnosis code for lung cancer within 90 days of each other between 1/1/2015 and 31/3/2018. Excluded: pts receiving chemotherapy suitable for SCLC. Data were stratified by CNS mets status. Data that could be linked to the social security administration (SSA) death file were used for mortality analyses. Results: Of 578 pts (median age 63 yrs, 64% female), 275 (48%) had CNS mets and 303 (52%) had no CNS mets. Of the pts with CNS mets, 149 (54%) discontinued 1L EGFRTKI, of whom 124 (83%) initiated 2L therapy; 121 (40%) pts with no CNS mets discontinued 1L, 85 (70%) of whom initiated 2L therapy. The most frequently prescribed 1L EGFR-TKI was erlotinib (n ¼ 414, 72%). Overall, at 1L, 6% of pts received an add-on therapy, bevacizumab (n ¼ 17, 3%) being the most common. The most frequent 2L therapy was osimertinib (n ¼ 96, 46%). In pts with available SSA mortality data,
doi:10.1093/annonc/mdz446 | ix199
Annals of Oncology Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca. D. Planchard: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, MedImmune, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Honoraria (self): AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Research grant / Funding (institution): AstraZeneca, Bristol-Myers Squibb, AbbVie, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, MedImmune, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo; Travel / Accommodation / Expenses: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim , Roche, Merck, Novartis, prIME Oncology, Pfizer. J.F. Vansteenkiste: Research grant / Funding (institution): MSD; Advisory / Consultancy: – Apotex, AstraZeneca, Boehringer Ingelheim, MSD, Novartis, Roche; Speaker Bureau / Expert testimony: – AstraZeneca, BMS, MSD, Roche. J.E. Gray: Honoraria (self): AstraZeneca, Bristol-Myers Squibb, Takeda; Advisory / Consultancy: Bristol-Myers Squibb, Celgene, Takeda; Research grant / Funding (institution): Array, Merck, AstraZeneca, Genentech, Boehringer Ingelheim, Bristol-Myers Squibb. R. Shah: Honoraria (self), Travel / Accommodation / Expenses: Boehringer Ingelheim, Roche, AstraZeneca. P.K. Cheema: Honoraria (self), Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Merck, Takeda, Novartis, Genomic Health, Pfizer. M. Tiseo: Advisory / Consultancy: AstraZeneca, Bristol-Myers Squibb, MSD, Boehringer Ingelheim, Takeda; Research grant / Funding (institution): AstraZeneca, Boehringer Ingelheim. T. John: Advisory / Consultancy: Roche, BristolMyers Squibb, Merck, Ignyta, AstraZeneca, Takeda, Boehringer Ingelheim, Pfizer. R. Hodge: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. Y. Rukazenkov: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. J. Soria: Advisory / Consultancy: AstraZeneca, Astex, Clovis, GSK, GamaMabs, Lilly, MSD, Mission Therapeutics, Merus, Pfizer, PharmaMar, Pierre Fabre, Roche/Genentech, Sanofi, Servier, Symphogen, Takeda; Shareholder / Stockholder / Stock options: AstraZeneca, Gritstone; Full / Parttime employment: AstraZeneca. F. Imamura: Honoraria (self), Research grant / Funding (institution): AstraZeneca. S.S. Ramalingam: Honoraria (self), Advisory / Consultancy: AstraZeneca, Amgen, Bristol-Myers Squibb, Merck, Roche/Genentech, Loxo, Nektar, Tesaro; Research grant / Funding (institution): AstraZeneca, Amgen, Bristol-Myers Squibb, Merck, Tesaro, Advaxis, Takeda.
LBA17
Longitudinal circulating tumour DNA (ctDNA) monitoring for early detection of disease progression and resistance in advanced NSCLC in FLAURA
T. Reungwetwattana1, J. Gray2, A. Markovets3, N. Nogami4, J.S. Lee5, B.C. Cho6, B. Chewaskulyong7, M. Majem8, N. Peled9, K. Vishwanathan10, A. Todd11, Y. Rukazenkov12, M. Johnson13, C. Barrett3, J. Chmielecki3, R. Hartmaier3, S. Ramalingam14 1 Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, 2Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA, 3 Translational Medicines, Research and Early Development, Oncology R&D, AstraZeneca, Boston, MA, USA, 4Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan, 5Department of Medical Oncology, Seoul National University Bundang Hospital, Seoul, Republic of Korea, 6 Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea, 7Oncology Unit, Department of Medicine, Chiang Mai University, Chiang Mai, Thailand, 8Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, 9Soroka Cancer Center, Ben-Gurion University, Beer Sheva, Israel, 10Clinical Pharmacology and Safety Science, R&D, AstraZeneca, Boston, MA, USA, 11Oncology Biometrics, Oncology R&D, AstraZeneca, Cambridge, UK, 12Oncology R&D, AstraZeneca, Cambridge, UK, 13 Quantitative Clinical Pharmacology, Research and Early Development, Oncology R&D, AstraZeneca, Cambridge, UK, 14Winship Cancer Institute, Emory University, Atlanta, GA, USA Background: In the phase III FLAURA study (NCT02296125), the 3rd-generation EGFR-TKI osimertinib showed superior efficacy to comparator EGFR-TKIs in previously untreated EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC). Here we report results from an exploratory analysis of ctDNA for the early detection of disease progression (PD) in FLAURA. Methods: Treatment-naı¨ve patients (pts) with EGFRm (ex19del/L858R) locally advanced/metastatic NSCLC (n ¼ 556) were randomised 1:1 (osimertinib 80 mg qd: comparator [gefitinib 250 mg qd/erlotinib 150 mg qd]). Plasma samples were collected on Days 1, 8 and 15, then every 21 days for weeks (W) 3–18, then every 6W thereafter. In pts who had a plasma sample on PD and/or discontinuation, ctDNA droplet digital PCR (ddPCR; Biodesix) for EGFRm (ex19del/L858R/T790M) was performed at all available time points and C797S for post-W6 time points. C797S and T790M were the only resistance mutations assayed. ctDNA progression was defined with respect to the nadir ctDNA result and its proximity to the ddPCR detection and quantification limits. Results: The ctDNA progression analysis included 122/556 (22%) pts with valid longitudinal monitoring ddPCR data and RECIST PD by DCO1 (12 June 2017). Across both arms, ctDNA progression preceded or co-occurred with PD in 80/122 (66%) pts with 2.7 months (mo) median lead time; 9.5 mo median progression-free survival (mPFS; n ¼ 80). Acquired C797S or T790M was detected in 57/122 (47%) pts with ctDNA progression (osimertinib 4/50 [8%] C797S, comparator 53/72 [74%] T790M); median time to detection was 16.7 and 8.4 mo for the osimertinib and comparator arms, respectively, mirroring overall mPFS. In pts with ctDNA progression and PD (n ¼ 106), acquired T790M and C797S were detected either at the same time as, or earlier than PD in 41/106 (38%) pts (osimertinib 2/39 [5%], comparator 39/67 [58%]); median lead time was 1.4 mo. Conclusions: ctDNA monitoring may allow for earlier identification of pts who progress on first-line EGFR-TKI therapy and the detection of EGFR-mediated resistance mechanisms in advance of PD in EGFRm NSCLC. Future work aims to explore early detection of non-EGFR-mediated resistance.
Volume 30 | Supplement 9 | November 2019
Clinical trial identification: NCT02296125. Editorial acknowledgement: Donna Tillotson, PhD, of iMed Comms, Macclesfield, UK, an Ashfield Company, part of UDG Healthcare plc, funded by AstraZeneca in accordance with Good Publications Practice (GPP3) guidelines. Legal entity responsible for the study: AstraZeneca. Funding: AstraZeneca. Disclosure: J.E. Gray: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Array; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Takeda. A. Markovets: Shareholder / Stockholder / Stock options, Full / Parttime employment: AstraZeneca. N. Nogami: Honoraria (self): Pfizer Inc., Chugai Pharmaceutical Co. Ltd, Eli Lilly, Taiho Pharmaceutical Co. Ltd., AstraZeneca, Kyowa Hakko Kirin, Ono Pharmaceutical Co. Ltd., Bristol-Myers Squibb, MSD. B.C. Cho: Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Janssen, Yuhan, Ono Pharmaceutical, Dizal Pharma, MSD; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Licensing / Royalties: Champions Oncology; Honoraria (institution), Advisory / Consultancy: Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Pfizer, Eli Lilly, Takeda; Shareholder / Stockholder / Stock options: TheraCanVac Inc. B. Chewaskulyong: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca. M. Majem: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy: Tesaro; Speaker Bureau / Expert testimony: Hellsin; Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pierre Fabre; Speaker Bureau / Expert testimony: Amgen. N. Peled: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Novartis, Pfizer, Roche, Takeda; Advisory / Consultancy: Eli Lilly; Honoraria (self): Foundation Medicine; Shareholder / Stockholder / Stock options: Novellus Dx; Honoraria (self): Guardant360. K. Vishwanathan: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. A. Todd: Full / Part-time employment: AstraZeneca. Y. Rukazenkov: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. M. Johnson: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. C. Barrett: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. J. Chmielecki: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. R. Hartmaier: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca; Shareholder / Stockholder / Stock options, Licensing / Royalties, Nfe2l2 exon 2 ano/or exon 3 loss from work conducted at Foundation Medicine; provisional patent filed: Foundation Medicine. S.S. Ramalingam: Advisory / Consultancy, Research grant / Funding (self): Amgen, AstraZeneca, Bristol-Myers Squibb, Merck; Advisory / Consultancy: AbbVie, Celgene, Genentech, Lilly, Loxo, Takeda; Research grant / Funding (self): Tesaro.
LBA18
Survival and treatment patterns in patients (pts) with locally advanced or metastatic NSCLC treated with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIS): Analysis of US insurance claims databases
R. Soo1, T. Seto2, J.E. Gray3, P. Karimi4, A. Taylor5, W. Sawyer6, E. Thiel7, E. Marchlewicz7, M. Brouillette7 1 Department Haematology-Oncology, National University Hospital, Singapore, 2 Thoracic Oncology, NHO Kyushu Cancer Center, Fukuoka, Japan, 3Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA, 4 Oncology Business Unit, AstraZeneca, Gaithersburg, MD, USA, 5Oncology Business Unit, AstraZeneca, Cambridge, UK, 6Biometrics Oncology, AstraZeneca, Cambridge, UK, 7 Custom Data Analytics, IBM Watson Health, Cambridge, MA, USA Background: Most pts with EGFR mutation-positive (EGFRm) NSCLC develop firstline (1L) EGFR-TKI resistance. Previous analyses of US insurance databases have studied healthcare utilisation and expenditure in pts with EGFRm NSCLC starting first-/second-generation (1G/2G) EGFR-TKIs. We examined treatment patterns and survival rates among pts with locally advanced/metastatic NSCLC, who received 1L 1G/ 2G EGFR-TKIs, in a retrospective analysis of data from the MarketScan Commercial and Medicare Supplemental databases (all US census regions). We also assessed the effect of central nervous system metastases (CNS mets) on survival rates. Methods: Pts 18 yrs with EGFRm NSCLC who received 1L 1G/2G EGFR-TKI were analysed from date of first lung cancer diagnosis (index date) through a variable-length follow-up period. Pts included had 1 pharmacy claim for 1G/2G EGFR-TKI on/ within 60 days post index, and 2 non-diagnostic claims with a diagnosis code for lung cancer within 90 days of each other between 1/1/2015 and 31/3/2018. Excluded: pts receiving chemotherapy suitable for SCLC. Data were stratified by CNS mets status. Data that could be linked to the social security administration (SSA) death file were used for mortality analyses. Results: Of 578 pts (median age 63 yrs, 64% female), 275 (48%) had CNS mets and 303 (52%) had no CNS mets. Of the pts with CNS mets, 149 (54%) discontinued 1L EGFRTKI, of whom 124 (83%) initiated 2L therapy; 121 (40%) pts with no CNS mets discontinued 1L, 85 (70%) of whom initiated 2L therapy. The most frequently prescribed 1L EGFR-TKI was erlotinib (n ¼ 414, 72%). Overall, at 1L, 6% of pts received an add-on therapy, bevacizumab (n ¼ 17, 3%) being the most common. The most frequent 2L therapy was osimertinib (n ¼ 96, 46%). In pts with available SSA mortality data,
doi:10.1093/annonc/mdz446 | ix199