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Background The ongoing phase III ARCHER 1050 study (NCT01774721) compared dacomitinib (daco) with gefitinib (gef) as first-line therapy for pts with advanced epidermal growth factor receptor-positive (EGFR+) non-small cell lung cancer (NSCLC). Progression-free survival, duration of response, and OS significantly improved with daco vs gef. The improvement in OS was previously reported after median follow-up of 31.3 months (mo) with 220 (48.7%) total deaths. Here, final OS results are reported after a median follow-up of 47.9 mo in ARCHER 1050 to evaluate the persistence of OS improvement with daco. Methods Pts with newly diagnosed EGFR+ NSCLC were randomized 1:1 to daco or gef. Randomization was stratified by race and EGFR mutation type. Results Over a median follow-up of 47.9 mo as of 13 May 2019, 285 deaths occurred (133 [58.6%] in the daco arm [n = 227] and 152 [67.6%] in the gef arm [n = 225]). OS was still significantly improved with daco vs gef (stratified hazard ratio [HR], 0.748; 95% confidence interval [CI], 0.591–0.947; 2-sided P = 0.0155). Median OS (95% CI) with daco was 34.1 mo (29.5–39.8) vs 27.0 mo (24.4–31.6) with gef. OS30 was 56.4% with daco and 45.7% with gef. Median OS, unstratified HR, and P values for interaction are also reported by race and EGFR mutation type (Table). Dose reductions occurred in 154 (67.8%) pts receiving daco; median OS (95% CI) in pts with and without dose reductions was 42.5 (36.7–not estimable [NE]) and 20.7 (15.4–25.6) mo, respectively. In pts reduced to a lowest daco dose of 30 mg (n = 89) and 15 mg (n = 65), median OS was 36.7 mo (28.8–44.7) and NE (40.1 mo–NE), respectively. Conclusions With extended follow-up (median 47.9 mo), daco continues to improve OS over gef in pts with advanced EGFR+ NSCLC; the same trend was observed in most subgroups defined by race and EGFR status. The benefit of OS was maintained in patients who received dose reductions. Table: LBA19 Overall survival by demographics (ITT population)   Events/N (%)   Median a (month)   HR (95% CI) (Unstratified)  P b   Daco  Gef  Daco  Gef  Overall  133/227 (58.6)  152/225 (67.6)  34.1  27.0  0.775 (0.614–0.978)    Race per CRF Asian Mainland Chinese Japanese other East Asian Non-Asian  95/170 (55.9) 69/114 (60.5) 22/40 (55.0) 4/16 (25.0) 38/57 (66.7)  115/176 (65.3) 87/117 (74.4) 22/41 (53.7) 6/18 (33.3) 37/49 (75.5)  37.7 32.5 42.2 NE 29.5  29.1 24.9 44.8 NE 20.6  0.759 (0.578–0.996) 0.687 (0.501–0.943) 0.985 (0.546–1.780) 0.787 (0.222–2.791) 0.758 (0.480–1.196)  0.9886 c   EGFR at randomization Exon 19 deletion Exon 21 L858R substitution mutation  73/134 (54.5) 60/93 (64.5)  82/133 (61.7) 70/92 (76.1)  36.7 32.5  30.8 23.2  0.847 (0.618, 1.161) 0.665 (0.470, 0.941)  0.3292    Events/N (%)   Median a (month)   HR (95% CI) (Unstratified)  P b   Daco  Gef  Daco  Gef  Overall  133/227 (58.6)  152/225 (67.6)  34.1  27.0  0.775 (0.614–0.978)    Race per CRF Asian Mainland Chinese Japanese other East Asian Non-Asian  95/170 (55.9) 69/114 (60.5) 22/40 (55.0) 4/16 (25.0) 38/57 (66.7)  115/176 (65.3) 87/117 (74.4) 22/41 (53.7) 6/18 (33.3) 37/49 (75.5)  37.7 32.5 42.2 NE 29.5  29.1 24.9 44.8 NE 20.6  0.759 (0.578–0.996) 0.687 (0.501–0.943) 0.985 (0.546–1.780) 0.787 (0.222–2.791) 0.758 (0.480–1.196)  0.9886 c   EGFR at randomization Exon 19 deletion Exon 21 L858R substitution mutation  73/134 (54.5) 60/93 (64.5)  82/133 (61.7) 70/92 (76.1)  36.7 32.5  30.8 23.2  0.847 (0.618, 1.161) 0.665 (0.470, 0.941)  0.3292  a Kaplan-Meier estimate; b P interaction; c P for interaction of treatment by Asian vs non-Asian CI, confidence interval; CRF, case report form; daco, dacomitinib; ECOG PS, Eastern Cooperative Oncology Group Performance Status; EGFR, epidermal growth factor receptor; gef, gefitinib; HR, Hazard ratio; ITT, intention-to-treat, NE, not estimable. Table: LBA19 Overall survival by demographics (ITT population)   Events/N (%)   Median a (month)   HR (95% CI) (Unstratified)  P b   Daco  Gef  Daco  Gef  Overall  133/227 (58.6)  152/225 (67.6)  34.1  27.0  0.775 (0.614–0.978)    Race per CRF Asian Mainland Chinese Japanese other East Asian Non-Asian  95/170 (55.9) 69/114 (60.5) 22/40 (55.0) 4/16 (25.0) 38/57 (66.7)  115/176 (65.3) 87/117 (74.4) 22/41 (53.7) 6/18 (33.3) 37/49 (75.5)  37.7 32.5 42.2 NE 29.5  29.1 24.9 44.8 NE 20.6  0.759 (0.578–0.996) 0.687 (0.501–0.943) 0.985 (0.546–1.780) 0.787 (0.222–2.791) 0.758 (0.480–1.196)  0.9886 c   EGFR at randomization Exon 19 deletion Exon 21 L858R substitution mutation  73/134 (54.5) 60/93 (64.5)  82/133 (61.7) 70/92 (76.1)  36.7 32.5  30.8 23.2  0.847 (0.618, 1.161) 0.665 (0.470, 0.941)  0.3292    Events/N (%)   Median a (month)   HR (95% CI) (Unstratified)  P b   Daco  Gef  Daco  Gef  Overall  133/227 (58.6)  152/225 (67.6)  34.1  27.0  0.775 (0.614–0.978)    Race per CRF Asian Mainland Chinese Japanese other East Asian Non-Asian  95/170 (55.9) 69/114 (60.5) 22/40 (55.0) 4/16 (25.0) 38/57 (66.7)  115/176 (65.3) 87/117 (74.4) 22/41 (53.7) 6/18 (33.3) 37/49 (75.5)  37.7 32.5 42.2 NE 29.5  29.1 24.9 44.8 NE 20.6  0.759 (0.578–0.996) 0.687 (0.501–0.943) 0.985 (0.546–1.780) 0.787 (0.222–2.791) 0.758 (0.480–1.196)  0.9886 c   EGFR at randomization Exon 19 deletion Exon 21 L858R substitution mutation  73/134 (54.5) 60/93 (64.5)  82/133 (61.7) 70/92 (76.1)  36.7 32.5  30.8 23.2  0.847 (0.618, 1.161) 0.665 (0.470, 0.941)  0.3292  a Kaplan-Meier estimate; b P interaction; c P for interaction of treatment by Asian vs non-Asian CI, confidence interval; CRF, case report form; daco, dacomitinib; ECOG PS, Eastern Cooperative Oncology Group Performance Status; EGFR, epidermal growth factor receptor; gef, gefitinib; HR, Hazard ratio; ITT, intention-to-treat, NE, not estimable. Clinical trial identification NCT01774721. Editorial acknowledgement Jessica Yuan (inScience Communications, Springer Healthcare, New York, NY, USA). Legal entity responsible for the study Pfizer Inc. Funding Pfizer Inc. and SFJ Pharmaceuticals® Disclosure T.S.K. Mok: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: ACEA Pharma; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Alpha Biopharma Co. Ltd.; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amoy Diagnostics Co. Ltd.; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, before 1/1/19: AstraZeneca ; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: BI; Honoraria (self), Advisory / Consultancy: Blueprint Medicines Corporation; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: CStone Pharmaceuticals; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Honoraria (self), Advisory / Consultancy: Fishawack Facilitate Ltd; Honoraria (self), Advisory / Consultancy: Hengrui Therapeutics Inc.; Honoraria (self), Advisory / Consultancy: Ignyta, Inc.; Honoraria (self), Advisory / Consultancy, Sept 2019: Incyte Corporation; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: InMed Medical Communication; Honoraria (self), Advisory / Consultancy, Jun 2019: Iqvia; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Loxo-Oncology; Honoraria (self), Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): MSD; Honoraria (self), Advisory / Consultancy: MoreHealth; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy: OncoGenex Pharmaceuticals, Inc.; Honoraria (self), Advisory / Consultancy: OrigiMed; Honoraria (self), Advisory / Consultancy: PeerVoice; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: PrIME Oncology; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche/Genentech; Honoraria (self), Advisory / Consultancy: Sanofi-Aventis R&D; Honoraria (self), Advisory / Consultancy: SFJ Pharmaceutical Ltd.; Honoraria (self), Advisory / Consultancy: Takeda Pharmaceuticals HK Ltd.; Honoraria (self), Advisory / Consultancy: Vertex Pharmaceuticals; Honoraria (self), Advisory / Consultancy: Yuhan Corporation; Advisory / Consultancy: Cirina; Advisory / Consultancy, uncompensated: GeneDecode Co. Ltd.; Speaker Bureau / Expert testimony: Taiho; Speaker Bureau / Expert testimony: Takeda Oncology; Leadership role, Officer / Board of Directors, Remunerated: AstraZeneca PLC; Leadership role, Officer / Board of Directors, Remunerated: Hutchison Chi-Med; Leadership role, Officer / Board of Directors, Non-remunerated: American Society of Clinical Oncology; Leadership role, Officer / Board of Directors, Non-remunerated: Asian Thoracic Oncology Research Group ; Leadership role, Officer / Board of Directors, Non-remunerated: Chinese Lung Cancer Research Foundation Limited; Leadership role, Officer / Board of Directors, Non-remunerated: Chinese Society of Clinical Oncology; Leadership role, Officer / Board of Directors, Non-remunerated: Hong Kong Cancer Fund; Leadership role, Officer / Board of Directors, Non-remunerated: Hong Kong Cancer Therapy Society ; Leadership role, Officer / Board of Directors, term ended on 30/4/19: International Association for the Study of Lung Cancer ; Research grant / Funding (institution): Clovis Oncology; Research grant / Funding (institution): Roche; Research grant / Funding (institution): SFJ; Research grant / Funding (institution): XCovery; Shareholder / Stockholder / Stock options, Shareholder: Hutchison Chi-Med; Shareholder / Stockholder / Stock options, Shareholder: Sanomics Ltd.; Shareholder / Stockholder / Stock options, now Biolidics Ltd.; Stock option: Clearbridge Biomedics; Shareholder / Stockholder / Stock options, Stock option: Loxo-Oncology; Shareholder / Stockholder / Stock options, Stock option: OrigiMed Co. Ltd.; Shareholder / Stockholder / Stock options, Stock option: Virtus Medical Group; Research grant / Funding (institution): AstraZeneca. K.H. Lee: Advisory / Consultancy: MSD; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS. K. Nakagawa: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Astellas Pharma Inc.; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Takeda Pharmaceutical Co. Ltd; Honoraria (self), Research grant / Funding (institution): AstraZeneca K.K.; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (institution): MSD K.K.; Honoraria (self), Research grant / Funding (institution): Eli Lilly Japan K.K.; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (institution): Nippon Boehringer Ingelheim Co. Ltd.; Honoraria (self), Research grant / Funding (institution): Daiichi Sankyo Co. Ltd.; Honoraria (self), Research grant / Funding (institution): Novartis Pharma K.K.; Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (institution): Pfizer Japan Inc.; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb Company; Honoraria (self): Nikkei Business Publications, Inc.; Honoraria (self): Kyorin Pharmaceutical Co. Ltd.; Honoraria (self): Medicus Shuppan, Publishers Co. Ltd.; Honoraria (self): CareNet, Inc; Honoraria (self): Thermo Fisher Scientific K.K.; Honoraria (self): Nichi-Iko Pharmaceutical Co. Ltd.; Honoraria (self): Nanzando Co. Ltd; Honoraria (self): Hisamitsu Pharmaceutical Co. Inc; Honoraria (self): Medical Review Co. Ltd.; Honoraria (self): Yodosha Co. Ltd; Honoraria (self): Yomiuri Telecasting Corporation; Research grant / Funding (institution): Icon Japan K.K.; Research grant / Funding (institution): Quintiles Inc.; Research grant / Funding (institution): CMIC Shift Zero K.K.; Research grant / Funding (institution): Eisai Co. Ltd.; Research grant / Funding (institution): Parexel International Corp.; Research grant / Funding (institution): Kissei Pharmaceutical Co. Ltd.; Research grant / Funding (institution): Iqvia; Research grant / Funding (institution): Kyowa Hakko Kirin Co. Ltd; Research grant / Funding (institution): EPS Corporation; Research grant / Funding (institution): SymBio Pharmaceuticals Limited; Research grant / Funding (institution): Bayer Yakuhin, Ltd; Research grant / Funding (institution): Merck Serono Co. Ltd.; Research grant / Funding (institution): A2 Healthcare Corp.; Research grant / Funding (institution): AbbVie Inc.. S. Niho: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self): Chugai; Honoraria (self): Taiho; Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (institution): Eli Lilly; Honoraria (self): Novartis; Honoraria (self): Boehringer Ingelheim; Research grant / Funding (institution): Merck Serono. R. Linke: Full / Part-time employment: SFJ Pharmaceuticals®. M.R. Migliorino: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BI; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche. A. Pluzanski: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp & Dohme; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche. K. Noonan: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. Y. Tang: Full / Part-time employment: Pfizer Inc. K.D. Wilner: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc. Y. Wu: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self): Eli Lilly; Honoraria (self): Pfizer; Honoraria (self): MSD; Honoraria (self): BMS. [ABSTRACT FROM AUTHOR]

Background In the ongoing phase 3 comparison of dacomitinib (daco) and gefitinib (gef) (ARCHER 1050; NCT01774721) as first-line therapy for EGFR-mutation-positive (EGFR+) advanced NSCLC, daco was associated with significant improvement in progression free survival (PFS) and overall survival (OS). Here we present results for the subset of Asian patients (pts). Methods Eligible pts with newly diagnosed stage IIIB/IV or recurrent EGFR+ advanced NSCLC were randomized (1:1) to oral daco 45 mg once daily or gef 250 mg. Randomization was stratified by race and EGFR mutation (exon 19 del/exon 21 L858R) status. The primary efficacy endpoint was PFS by blinded independent radiologic central review (BIRC). Secondary endpoints were OS, objective response rate (ORR) and duration of response (DOR) by BIRC, and safety. Results Of 346 Asian pts, 170 were randomized to daco treatment and 176 to gef. Demographics and baseline characteristics of the groups were well balanced. At the July 29, 2016 data cutoff, the hazard ratio for PFS was 0.510 (95% confidence interval [CI] 0.392, 0.664), favoring daco (2-sided p value < 0.0001). Median PFS was 16.5 months (95% CI 12.9, 18.4) for daco and 9.3 months for gef (95% CI 9.2, 11.0). OS, ORR and DOR are shown in the table. Treatment-related adverse events (TRAEs) occurring in ≥ 50% of daco-treated pts were diarrhea (88.2%), paronychia (64.7%), and dermatitis acneiform (56.5%). In the gef arm, diarrhea (52.3%) was the only TRAE that occurred in ≥ 50% of pts. The daco dose was reduced in 67.6% of pts associated with adverse events (AEs); gef dose was reduced to every other day dosing in 9.7% of pts associated with AEs. Conclusions First-line daco was associated with significant prolongation of PFS compared with gef in Asian pts with EGFR+ advanced NSCLC. Daco treatment showed improved OS, ORR, and DOR compared to gef treatment. The AE profile for daco and gef in Asian pts was consistent with the overall ARCHER 1050 study. Table: 480P Key secondary endpoints   Dacomitinib N = 170  Gefitinib N = 176  Median overall survival, months (95% CI) a   34.2 (30.1, NE  29.1 (25.2,NE)  Objective response rate, % (95% CI)  77.1 (70.0, 83.1)  72.7 (65.5, 79.2)  ---Patients with complete response (n, %)  9 (5.3)  4 (2.3)  ---Patients with partial response (n, %)  122 (71.8)  124 (70.5)  Median duration of response, months (95% CI)  16.6 (13.8, 30.4)  8.3 (8.1, 10.2)    Dacomitinib N = 170  Gefitinib N = 176  Median overall survival, months (95% CI) a   34.2 (30.1, NE  29.1 (25.2,NE)  Objective response rate, % (95% CI)  77.1 (70.0, 83.1)  72.7 (65.5, 79.2)  ---Patients with complete response (n, %)  9 (5.3)  4 (2.3)  ---Patients with partial response (n, %)  122 (71.8)  124 (70.5)  Median duration of response, months (95% CI)  16.6 (13.8, 30.4)  8.3 (8.1, 10.2)  CI, confidence interval; N/n;number of patients; NE; not estimable. a Feb 17, 2017 was the data cutoff for final OS analysis. Table: 480P Key secondary endpoints   Dacomitinib N = 170  Gefitinib N = 176  Median overall survival, months (95% CI) a   34.2 (30.1, NE  29.1 (25.2,NE)  Objective response rate, % (95% CI)  77.1 (70.0, 83.1)  72.7 (65.5, 79.2)  ---Patients with complete response (n, %)  9 (5.3)  4 (2.3)  ---Patients with partial response (n, %)  122 (71.8)  124 (70.5)  Median duration of response, months (95% CI)  16.6 (13.8, 30.4)  8.3 (8.1, 10.2)    Dacomitinib N = 170  Gefitinib N = 176  Median overall survival, months (95% CI) a   34.2 (30.1, NE  29.1 (25.2,NE)  Objective response rate, % (95% CI)  77.1 (70.0, 83.1)  72.7 (65.5, 79.2)  ---Patients with complete response (n, %)  9 (5.3)  4 (2.3)  ---Patients with partial response (n, %)  122 (71.8)  124 (70.5)  Median duration of response, months (95% CI)  16.6 (13.8, 30.4)  8.3 (8.1, 10.2)  CI, confidence interval; N/n;number of patients; NE; not estimable. a Feb 17, 2017 was the data cutoff for final OS analysis. Clinical trial identification NCT01774721. Editorial acknowledgement Medical writing support was provided by Michelle Daniels (inScience Communications, Springer Healthcare, Philadelphia, PA, USA). Legal entity responsible for the study Pfizer Inc. Funding Pfizer Inc. Disclosure T.S.K. Mok: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: ACEA Pharma; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Alpha Biopharma Co. Ltd.; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amoy Diagnostics Co. LTD.; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, before 1/1/19: AstraZeneca; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: BI; Honoraria (self), Advisory / Consultancy: Blueprint Medicines Corporation; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: CStone Pharmaceuticals; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Honoraria (self), Advisory / Consultancy: Fishawack Facilitate Ltd; Honoraria (self), Advisory / Consultancy: Hengrui Therapeutics Inc.; Honoraria (self), Advisory / Consultancy: Ignyta, Inc.; Honoraria (self), Advisory / Consultancy, Sept 2019: Incyte Corporation; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: InMed Medical Communication; Honoraria (self), Advisory / Consultancy, Jun 2019: IQVIA; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Loxo-Oncology; Honoraria (self), Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): MSD; Honoraria (self), Advisory / Consultancy: MoreHealth; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy: OncoGenex Pharmaceuticals, Inc.; Honoraria (self), Advisory / Consultancy: OrigiMed; Honoraria (self), Advisory / Consultancy: PeerVoice; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: PrIME Oncology; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche/Genentech; Honoraria (self), Advisory / Consultancy: Sanofi-Aventis R&D; Honoraria (self), Advisory / Consultancy: SFJ Pharmaceutical Ltd.; Honoraria (self), Advisory / Consultancy: Takeda Pharmaceuticals HK Ltd.; Honoraria (self), Advisory / Consultancy: Vertex Pharmaceuticals; Honoraria (self), Advisory / Consultancy: Yuhan Corporation; Advisory / Consultancy: Cirina; Advisory / Consultancy, uncompensated: geneDecode Co. Ltd.; Speaker Bureau / Expert testimony: Taiho; Speaker Bureau / Expert testimony: Takeda Oncology; Leadership role, Officer / Board of Directors, Remunerated: AstraZeneca PLC; Leadership role, Officer / Board of Directors, Remunerated: Hutchison Chi-Med; Leadership role, Officer / Board of Directors, Non-remunerated: American Society of Clinical Oncology; Leadership role, Officer / Board of Directors, Non-remunerated: Asian Thoracic Oncology Research Group; Leadership role, Officer / Board of Directors, Non-remunerated: Chinese Lung Cancer Research Foundation Limited; Leadership role, Officer / Board of Directors, Non-remunerated: Chinese Society of Clinical Oncology; Leadership role, Officer / Board of Directors, Non-remunerated: Hong Kong Cancer Fund; Leadership role, Officer / Board of Directors, Non-remunerated: Hong Kong Cancer Therapy Society; Leadership role, Officer / Board of Directors, term ended on 30/4/19: International Association for the Study of Lung Cancer ; Research grant / Funding (institution): Clovis Oncology; Research grant / Funding (institution): Roche; Research grant / Funding (institution): SFJ; Research grant / Funding (institution): XCovery; Shareholder / Stockholder / Stock options, Shareholder: Hutchison Chi-Med; Shareholder / Stockholder / Stock options, Shareholder: Sanomics Ltd.; Shareholder / Stockholder / Stock options, now Biolidics Ltd.; Stock option: Clearbridge Biomedics; Shareholder / Stockholder / Stock options, Stock option: Loxo-Oncology; Shareholder / Stockholder / Stock options, Stock option: OrigiMed Co. Ltd.; Shareholder / Stockholder / Stock options, Stock option: Virtus Medical Group; Research grant / Funding (institution): AstraZeneca. K.H. Lee: Advisory / Consultancy: MSD; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS. K. Nakagawa: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Astellas Pharma Inc.; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Takeda Pharmaceutical Co. Ltd; Honoraria (self), Research grant / Funding (institution): AstraZeneca K.K.; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical Co.Ltd.; Honoraria (self), Research grant / Funding (institution): MSD K.K.; Honoraria (self), Research grant / Funding (institution): Eli Lilly Japan K.K.; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (institution): Nippon Boehringer Ingelheim Co. Ltd.; Honoraria (self), Research grant / Funding (institution): Daiichi Sankyo Co. Ltd.; Honoraria (self), Research grant / Funding (institution): Novartis Pharma K.K.; Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (institution): Pfizer Japan Inc.; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self): Nikkei Business Publications, Inc.; Honoraria (self): Kyorin Pharmaceutical Co. Ltd.; Honoraria (self): Medicus Shuppan, Publishers Co. Ltd.; Honoraria (self): CareNet, Inc.; Honoraria (self): Thermo Fisher Scientific K.K.; Honoraria (self): Nichi-Iko Pharmaceutical Co. Ltd.; Honoraria (self): Nanzando Co. Ltd; Honoraria (self): Hisamitsu Pharmaceutical Co. Inc; Honoraria (self): Medical Review Co. Ltd.; Honoraria (self): Yodosha Co. Ltd; Honoraria (self): Yomiuri Telecasting Corporation; Research grant / Funding (institution): ICON Japan K.K.; Research grant / Funding (institution): Quintiles Inc.; Research grant / Funding (institution): CMIC Shift Zero K.K.; Research grant / Funding (institution): Eisai Co. Ltd.; Research grant / Funding (institution): Parexel International Corp.; Research grant / Funding (institution): Kissei Pharmaceutical Co. Ltd.; Research grant / Funding (institution): IQVIA; Research grant / Funding (institution): Kyowa Hakko Kirin Co. Ltd; Research grant / Funding (institution): EPS Corporation; Research grant / Funding (institution): SymBio Pharmaceuticals Limited; Research grant / Funding (institution): Bayer Yakuhin, Ltd; Research grant / Funding (institution): Merck Serono Co. Ltd.; Research grant / Funding (institution): A2 Healthcare Corp.; Research grant / Funding (institution): AbbVie Inc.. S. Niho: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self): Chugai; Honoraria (self): Taiho; Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (institution): Eli Lilly; Honoraria (self): Novartis; Honoraria (self): Boehringer Ingelheim; Research grant / Funding (institution): Merck Serono. R. Linke: Full / Part-time employment: SFJ Pharmaceuticals®. C.H. Wong: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. Y. Tang: Full / Part-time employment: Pfizer Inc. M. Singh: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. K.D. Wilner: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc. Y-L. Wu: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self): Eli Lilly; Honoraria (self): Pfizer; Honoraria (self): MSD; Honoraria (self): BMS. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background In AURA3 (NCT02151981), osimertinib, a 3rd-generation EGFR-TKI, significantly prolonged progressionfree survival (PFS) and improved response rate vs plt-pem in pts with centrally confirmed EGFR T790M advanced NSCLC and progression on a prior EGFR-TKI. Here we report mature OS data. Methods Adult pts were randomised 2:1 to receive oral osimertinib (80 mg once daily) or intravenous pem (500 mg per m2 of body surface area) + carboplatin (target area under the curve 5)/cisplatin (75 mg per m2), every 3 weeks, ≤6 cycles. Treatment beyond progression (RECIST 1.1) was allowed if clinical benefit continued. Pts receiving plt-pem could cross over to osimertinib on disease progression. Asymptomatic CNS metastases were allowed. Primary endpoint was investigator-assessed PFS. OS and safety are reported as secondary endpoints. Data cut-off (DCO): 15 March 2019. Results In total, 419 pts were randomised (osimertinib, n = 279; plt-pem, n = 140); 99 pts (71%) crossed over to osimertinib from plt-pem. At DCO, 188 pts (67%) in the osimertinib arm vs 93 pts (66%) in the plt-pem arm had died, including 66/99 (67%) crossover pts; median OS 26.8 mo (95% confidence interval [CI] 23.5, 31.5) vs 22.5 mo (95% CI 20.2, 28.8) respectively, hazard ratio (HR) 0.87 (95% CI 0.67, 1.12; p = 0.277); survival rate at 24 mo was 55% vs 43% and at 36 mo was 37% vs 30%. Time to first subsequent treatment showed a large, clinically meaningful numerical advantage towards osimertinib, HR 0.21 (95% CI 0.16, 0.28; p < 0.001); time to second subsequent treatment, HR 0.87 (95% CI 0.69, 1.11; p = 0.263). In both arms, 99% pts had any adverse event (AE). Any AE grade ≥3 causally related to study treatment was 9% vs 34% for osimertinib and plt-pem respectively. Most common AEs were diarrhoea, 44% (grade ≥3, 1%), and nausea, 49% (grade ≥3, 4%), with osimertinib and plt-pem respectively. Conclusions A numerical advantage in OS was observed for pts receiving osimertinib vs plt-pem, with the majority of pts in the plt-pem arm having crossed over to osimertinib. The safety profile of osimertinib remains consistent with previous findings. Clinical trial identification NCT02151981. Editorial acknowledgement Laura Crocker, BMedSci, of iMed Comms, an Ashfield Company, who provided medical writing support funded by AstraZeneca. Legal entity responsible for the study AstraZeneca. Funding AstraZeneca. Disclosure Y-L. Wu: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self): Eli Lilly; Honoraria (self): Pfizer; Honoraria (self): MSD; Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim. T.S.K. Mok: Honoraria (self): ACEA Pharma, Alpha Biopharma Co. Ltd. Amgen, Amoy Diagnostics Co. LTD. AstraZeneca (before 1/1/19), Bayer, BI, Blueprint Medicines Corporation, BMS, Celgene, CStone Pharmaceuticals, Eli Lilly, Fishawack Facilitate Ltd, Hengrui Therapeutics Inc. Ignyt; Advisory / Consultancy: ACEA Pharma, Alpha Biopharma Co. Ltd. Amgen, Amoy Diagnostics Co. LTD. AstraZeneca (before 1/1/19), Bayer, BI, Blueprint Medicines Corporation, BMS, Celgene, Cirina, CStone Pharmaceuticals, Eli Lilly, Fishawack Facilitate Ltd, geneDecode Co. Ltd. (un; Leadership role: AstraZeneca PLC, Hutchison Chi-Med; Research grant / Funding (institution): AstraZeneca, BMS, Clovis Oncology, MSD, Novartis, Pfizer, Roche, SFJ, XCovery; Shareholder / Stockholder / Stock options: Shareholder: Hutchison Chi-Med, Sanomics Ltd. Stock option: Clearbridge Biomedics (now Biolidics Ltd.), Loxo-Oncology, OrigiMed Co. Ltd. Virtus Medical Group; Full / Part-time employment: The Chinese University of Hong Kong; Officer / Board of Directors: Remunerated: AstraZeneca PLC, Hutchison Chi-Med Non-remunerated: American Society of Clinical Oncology (ASCO) Asian Thoracic Oncology Research Group (ATORG) Chinese Lung Cancer Research Foundation Limited (CLCRF) Chinese Society of Clinical Oncology (CS. J-Y. Han: Honoraria (self): Roche, AstraZeneca, Bristol-Myers Squibb, MSD, Takeda; Advisory / Consultancy: AstraZeneca, Bristol-Myers Squibb, MSD, Takeda, Pfizer, Novartis, Lilly; Research grant / Funding (self): Roche, Pfizer, Ono Pharmaceutical, Takeda. M-J. Ahn: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca, Merck, Sharp & Dohme, Ono Pharmaceutical, Lilly, Roche; Advisory / Consultancy: Alpha Pharmaceutical, Takeda. 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. S-W. Kim: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca. F.A. Shepherd: Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: AstraZeneca. J. Laskin: Research grant / Funding (institution): AstraZeneca, Roche, Boehringer Ingelheim, Pfizer; Honoraria (self): AstraZeneca, Roche, Pfizer. H. Akamatsu: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Honoraria (institution): Chugai; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Pfizer; Honoraria (self), Honoraria (institution): Boehringer Ingelheim. W-C. Su: Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Boehringer Ingelheim. T. John: Advisory / Consultancy: Roche, Bristol-Myers Squibb, Merck, Ignyta, AstraZeneca, Takeda, Boehringer Ingelheim, Pfizer. M. Sebastian: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca, Roche, Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer, Boehringer Ingelheim, Celgene, Takeda, Bristol-Myers Squibb, MSD; Honoraria (self), Advisory / Consultancy: Lilly. H. Mann: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. M. Miranda: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. G. Laus: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. Y. Rukazenkov: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. V. Papadimitrakopoulou: Honoraria (self): F Hoffman-La Roche; Advisory / Consultancy: Nektar Therapeutics, AstraZeneca Pharmaceuticals, Arrys Therapeutics, Merck&Co, LOXO Oncology, Araxes Pharma, F.Hoffman-LaRoche Ltd, Janssen Research Foundation, Bristol-Myers Squibb, Clovis Oncology, Eli Lilly &Co, Novartis Pharmaceuticals Corp. Takeda ; Research grant / Funding (institution): Eli Lilly &Co, Novartis, Merck, AstraZeneca Pharmaceuticals, F Hoffman-La Roche, Nektar Therapeutics, Janssen, Bristol-Myers Squibb, Checkmate, Incyte. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Acquired resistance (AR) to programmed cell death protein 1/programmed death-ligand 1 [PD-(L)1] blockade is frequent in non-small-cell lung cancer (NSCLC), occurring in a majority of initial responders. Patients with AR may have unique properties of persistent antitumor immunity that could be re-harnessed by investigational immunotherapies. The absence of a consistent clinical definition of AR to PD-(L)1 blockade and lack of uniform criteria for ensuing enrollment in clinical trials remains a major barrier to progress; such clinical definitions have advanced biologic and therapeutic discovery. We examine the considerations and potential controversies in developing a patient-level definition of AR in NSCLC treated with PD-(L)1 blockade. Taking into account the specifics of NSCLC biology and corresponding treatment strategies, we propose a practical, clinical definition of AR to PD-(L)1 blockade for use in clinical reports and prospective clinical trials. Patients should meet the following criteria: received treatment that includes PD-(L)1 blockade; experienced objective response on PD-(L)1 blockade (inclusion of a subset of stable disease will require future investigation); have progressive disease occurring within 6 months of last anti-PD-(L)1 antibody treatment or rechallenge with anti-PD-(L)1 antibody in patients not exposed to anti-PD-(L)1 in 6 months. • In NSCLC, acquired resistance to immunotherapy is common and poorly understood. • A uniform clinical definition is imperative to further characterize patients and develop a rational approach to overcoming acquired resistance. • The proposed definition seeks to unify language for future reports and clinical trials in NSCLC. • We also highlight specific areas of uncertainty in classification of acquired resistance that require urgent attention and could lead to further refinements in the future. [ABSTRACT FROM AUTHOR]

Background: The irreversible epidermal growth factor receptor (EGFR) inhibitors have demonstrated efficacy in NSCLC patients with activating EGFR mutations, but it is unknown if they are superior to the reversible inhibitors. Dacomitinib is an oral, small-molecule irreversible inhibitor of all enzymatically active HER family tyrosine kinases. Methods: The ARCHER 1009 (NCT01360554) and A7471028 (NCT00769067) studies randomized patients with locally advanced/metastatic NSCLC following progression with one or two prior chemotherapy regimens to dacomitinib or erlotinib. EGFR mutation testing was performed centrally on archived tumor samples. We pooled patients with exon 19 deletion and L858R EGFR mutations from both studies to compare the efficacy of dacomitinib to erlotinib. Results: One hundred twenty-one patients with any EGFR mutation were enrolled; 101 had activating mutations in exon 19 or 21. For patients with exon19/21 mutations, the median progression-free survival was 14.6 months [95% confidence interval (CI) 9.0-18.2] with dacomitinib and 9.6 months (95% CI 7.4-12.7) with erlotinib [unstratified hazard ratio (HR) 0.717 (95% CI 0.458-1.124), two-sided log-rank, P = 0.146]. The median survival was 26.6 months (95% CI 21.6-41.5) with dacomitinib versus 23.2 months (95% CI 16.0-31.8) with erlotinib [unstratified HR 0.737 (95% CI 0.431-1.259), two-sided log-rank, P = 0.265]. Dacomitinib was associated with a higher incidence of diarrhea and mucositis in both studies compared with erlotinib. Conclusions: Dacomitinib is an active agent with comparable efficacy to erlotinib in the EGFR mutated patients. The subgroup with exon 19 deletion had favorable outcomes with dacomitinib. An ongoing phase III study will compare dacomitinib to gefitinib in first-line therapy of patients with NSCLC harboring common activating EGFR mutations (ARCHER 1050; NCT01774721). [ABSTRACT FROM AUTHOR]

Background There is an expanding list of therapeutically relevant biomarkers for NSCLC and effective molecular profiling is paramount. We sought to comprehensively and prospectively evaluate the molecular epidemiology of NSCLC in Asia and ascertain the extent of access to relevant therapies. The study is being conducted by the Asian Thoracic Oncology Research Group (ATORG) – an academic co-operative lung cancer trials group in Asia. Methods ATORG-001 is a prospective, multi-centre study of NSCLC patients (pts) throughout Asia. Eligible pts must have good performance status (ECOG ≤2), adequate organ function and ≤3 prior lines of cytotoxic chemotherapy. Archival tissue specimens are sent to a central laboratory in Singapore (Singapore General Hospital) for profiling, consisting of NGS with the Oncomine Focus Assay (52 gene panel including fusions) and PD-L1 immunohistochemistry. Results are returned to investigators in a clinically relevant timeframe. Baseline demographics, pre-existing molecular profile and prior treatment details are collected. Treatment and pt outcomes are followed for 2 years. Recruitment commenced in Jan 2019 in 3 sites (National Cancer Centre Singapore, Chinese University of Hong Kong, University Malaya Medical Centre). We report an interim analysis for the first 27 of a planned 500 pts. Results As of 01 Jul 2019, 27 pts have enrolled with median age 67 yrs (range 46-79), 59% male, 81% adenocarcinoma, 52% stage IV, 37% non-smokers, median lines of prior therapy 1 (range 0-6) and 85% with no known oncogenic driver. Pre-existing mutation status was known in 89% for EGFR and 63% for ALK. Median turnaround time from tissue acquisition to profiling results was 22 days (range 15-74). New alterations were most common in KRAS (19%), MYC (15%), CDK4 (7%) and ERBB2 (7%). Potentially actionable new alterations were found in 7 (26%) pts, including KRAS G12C mutation (7%), BRAF G469A mutation (4%), ERBB2 exon 20 insertion (4%), ERBB2 amplification (4%), FGFR2 amplification (4%) and MET exon 14 skipping mutation (4%). Conclusions Enrolment is ongoing with additional sites and countries planned to comprehensively evaluate the molecular epidemiology of NSCLC in Asia. Legal entity responsible for the study Asian Thoracic Oncology Research Group. Funding Asian Thoracic Oncology Research Group, Novartis. Disclosure A.C. Tan: Travel / Accommodation / Expenses: ASLAN Pharmaceuticals. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]