Found 4 Presentations For Request "Ahn"
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Proffered Paper session III Proffered Paper session

105O - Osimertinib for patients (pts) with leptomeningeal metastases (LM) associated with EGFRm advanced NSCLC: The AURA LM study

Presentation Number
105O
Lecture Time
08:54 - 09:06
Speakers
  • M. Ahn (Seoul, Korea, Republic of)
Location
Room A, Geneva Palexpo, Geneva, Switzerland
Date
Fri, 12.04.2019
Time
08:30 - 10:00
Authors
  • M. Ahn (Seoul, Korea, Republic of)
  • C. Chiu (Taipei, Taiwan)
  • Y. Cheng (Changchun, Jilin, China)
  • J. Han (Goyang, KR, Korea, Republic of)
  • S. Goldberg (New Haven, United States of America)
  • A. Greystoke (Newcastle-upon-Tyne, Tyne and Wear, United Kingdom)
  • J. Crawford (Durham, NC, United States of America)
  • Y. Zhao (Zhengzhou, China)
  • X. Huang (Cambridge, United Kingdom)
  • M. Johnson (Cambridge, United Kingdom)
  • K. Vishwanathan (Waltham, United States of America)
  • A. Mendoza-Naranjo (Cambridge, United Kingdom)
  • T. Mok (Shatin, Hong Kong PRC)

Abstract

Background

Osimertinib, a 3rd-generation EGFR-TKI selective for both sensitising and EGFR T790M resistance mutations, has shown efficacy in pts with CNS metastases; encouraging activity has been reported in pts with LM at 160 mg once daily (QD) (BLOOM; NCT02228369). We report LM activity with osimertinib 80 mg QD in pts with LM from studies across the AURA program (NCT01802632; NCT02094261; NCT02442349; NCT02151981).

Methods

Pts with EGFR T790M positive advanced NSCLC and progression on EGFR-TKI received osimertinib 80 mg QD. Patients with LM and CNS metastases were eligible if asymptomatic and stable. Baseline brain scans were mandated in pts with known or treated CNS metastases at study entry; pts with evidence of LM by neuroradiological blinded independent review (BICR) were included for retrospective analysis. Follow-up brain scans were assessed for radiologic LM response by LM BICR per Response Assessment in Neuro-Oncology LM criteria. LM objective response rate (ORR), LM duration of response (DoR), LM progression-free survival (PFS) and overall survival (OS) were assessed retrospectively. Results are based on individual data cutoffs for each study. A longitudinal analysis overlaid changes from baseline non-CNS tumour size with LM responses at each visit for AURA LM and BLOOM LM pts.

Results

22 LM pts from the AURA studies were included for analysis. Median treatment exposure was 7.3 mo (range 2.3–16.5). Baseline characteristics were broadly consistent with the overall AURA study population: median age 58 yrs; female 59%; Asian 82%; WHO PS 1 82%. LM ORR was 55% (95% CI 32, 76); complete or partial LM response reported in 6 pts (27%) each. Median LM DoR was not reached (95% CI 2.8, not calculable [NC]). Median LM PFS was 11.1 mo (95% CI 4.6, NC). OS was 18.8 mo (95% CI 6.3, NC). Graphical assessment of longitudinal analysis showed similar non-CNS and LM responses in AURA LM and BLOOM LM pts.

Conclusions

Consistent with early efficacy outputs from BLOOM (160mg QD), osimertinib 80 mg QD showed a clinically meaningful benefit in pts with T790M-positive NSCLC and radiographically-detected LM. Additional studies are needed to further evaluate the CNS efficacy of osimertinib 80 mg QD in pts with EGFRm NSCLC and LM.

Clinical trial identification

AURA extension (NCT01802632), AURA2 (NCT02094261), AURA3 (NCT02151981), AURA17 (NCT02442349).

Editorial acknowledgement

Medical support was provided by Robert Harrison, PhD, of iMed Comms, Macclesfield, UK, an Ashfield Company, part of UDG Healthcare plc, and funded by AstraZeneca, Cambridge, UK, in accordance with Good Publications Practice (GPP3) guidelines.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

M-J. Ahn: Speakers’ bureau: AstraZeneca, MSD, ONO, Lilly, Roche; Consultant: Alpha Pharmaceutical. C-H. Chiu: Honorarium: AZ, BI, Novartis, Pfizer, Roche. J-Y. Han: Honoraria: Roche, AstraZeneca, BMS, MSD; Advisory role: AstraZeneca, BMS, MSD, Lilly, Novartis, Pfizer; Research fund: Roche, Pfizer, ONO. S.B. Goldberg: Research support: AstraZeneca; Advisory board member: AstraZeneca, Boehringer Ingelheim, Eli Lilly, Bristol-Myers Squibb, Genentech, Amgen, Spectrum. A. Greystoke: Consultancy fees, speaker fees: AstraZeneca. J. Crawford: Scientific advisor: Amgen, Enzychem, Merck, Pfizer; Consultant: Amgen, AstraZeneca, Coherus, Enzychem, Merck, Pfizer; Research support: AstraZeneca, Genentech, Helsinn; Chair/DSMB member: Beyond Spring, G1 Therapeutics, Janssen, Merrimack, Mylan, Roche. X. Huang, M. Johnson, K. Vishwanathan, A. Mendoza-Naranjo: Employee, shareholder: AstraZeneca. T.S.K. Mok: Leadership (for-profit): ChiMed, Sanomics Ltd.; Leadership (non-profit): IASLC, ASCO, Chinese Society of Clinical Oncology; Shareholder: Sanomics Ltd.; Honoraria: AZ, BI, Roche/Genentech, Pfizer, Lilly, Merck Serono, MSD, Novartis, SFJ, ACEA, Vertex, BMS, Oncogenex, Celgene, Ignyta, Cirina, Fishawack Facilitate, Takeda Oncology, Janssen, ChiMed; Consulting/advisory role: AZ, BI, Roche/Genentech, Pfizer, Lilly, Merck Serono, MSD, Novartis, SFJ Company, ACEA, Vertex, BMS, GeneDecode, Oncogenex, Celgene, Ignyta, Cirina, Fishawack Facilitate, Janssen, Takeda Oncolog, ChiMed; Research funding: AZ, BI, Pfizer, Novartis, SFJ, Roche, MSD, Clovis Oncology, BMS, Eisai, Taiho, Merck Serono, XCovery. All other authors have declared no conflicts of interest.

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Proffered Paper session I Proffered Paper session

LBA4 - Effect of post-study immunotherapy (IO) on overall survival (OS) outcome in patients with metastatic (m) NSCLC treated with first-line durvalumab (D) vs chemotherapy (CT) in the phase III MYSTIC study

Presentation Number
LBA4
Lecture Time
17:45 - 18:00
Speakers
  • N. Reinmuth (Gauting, Germany)
Location
Room C, Geneva Palexpo, Geneva, Switzerland
Date
Wed, 10.04.2019
Time
16:30 - 18:15
Authors
  • N. Reinmuth (Gauting, Germany)
  • B. Cho (Seoul, Korea, Republic of)
  • K. Lee (Cheongju, Korea, Republic of)
  • A. Luft (Saint-Petersburg, Russian Federation)
  • M. Ahn (Seoul, Korea, Republic of)
  • J. Schneider (Mineola, United States of America)
  • F. Shepherd (Toronto, Canada)
  • S. Geater (Hat Yai, Thailand)
  • Z. Pápai-Székely (Székesfehérvár, Hungary)
  • T. Van Ngoc (Ho Chi Minh, Viet Nam)
  • M. Garassino (Milan, Italy)
  • F. Liu (Gaithersburg, United States of America)
  • D. Clemett (Cambridge, United Kingdom)
  • P. Thiyagarajah (Cambridge, United Kingdom)
  • M. Ouwens (London, United Kingdom)
  • U. Scheuring (Melbourn, United Kingdom)
  • S. Peters (Lausanne, Switzerland)
  • N. Rizvi (New York, NY, United States of America)

Abstract

Background

In MYSTIC (NCT02453282), an open-label, Phase 3 study of first-line D (anti-PD-L1) ± tremelimumab vs platinum-based CT in mNSCLC, while not statistically significant, a clinically meaningful improvement in OS was seen with D vs CT in pts with tumour cell PD-L1 expression ≥25% (PD-L1 TC ≥25%; HR 0.76 [97.54% CI 0.56–1.02], p=0.036). Here we describe subsequent treatment patterns and explore the effect of subsequent IO on the OS outcome with D vs CT.

Methods

IO/CT-naïve mNSCLC pts were randomised to D (20 mg/kg i.v. q4w until disease progression) or CT (up to 6 cycles; pemetrexed maintenance permitted). In-study crossover from CT to D was not allowed. For D vs CT, the primary endpoint was OS in pts with PD-L1 TC ≥25%. Three statistical models were employed in exploratory analyses to evaluate the effect of subsequent (post-study) IO on the OS data: the rank preserving structural failure time (RPSFT) method, the inverse probability of censoring weighting (IPCW) method, and a 2-stage method.

Results

163 and 162 pts with PD-L1 TC ≥25% were randomised to D and CT, respectively. At data cut-off (04 Oct 2018), 44.8% of pts in the D arm and 58.6% of pts in the CT arm had received subsequent treatment (Table). Most pts started subsequent treatment within 2 mos of discontinuing study treatment. Among pts who received subsequent treatment, IO was administered to 10/73 (13.7%) pts in the D arm and 64/95 (67.4%) pts in the CT arm; most commonly nivolumab. Using the 2-stage method, which was the most appropriate for evaluating the effect of subsequent IO, OS was improved with D vs CT (HR 0.66 [95% CI 0.51, 0.86]).

Durvalumab (n=163)Chemotherapy (n=162)
Pts who received study treatment, n (%)161 (98.8)153 (94.4)
→Pts who discontinued study treatment136 (83.4)152 (93.8)
→Pts remaining on study treatment25 (15.3)1 (0.6)
Pts who received any subsequent treatment, n (%)73 (44.8)95 (58.6)
→Immunotherapy10 (6.1)64 (39.5)
→→Nivolumab3 (1.8)50 (30.9)
→→Pembrolizumab4 (2.5)11 (6.8)
→→Atezolizumab2 (1.2)3 (1.9)
→→Durvalumab02 (1.2)
→→Tremelimumab01 (0.6)
→→Other immunotherapy1 (0.6)2 (1.2)
→Cytotoxic chemotherapy70 (42.9)58 (35.8)
→Other systemic therapies*18 (11.0)18 (11.1)

Denominators for percentages are the number of pts randomised.

Excluding immunotherapy and cytotoxic chemotherapy.

Conclusions

In the MYSTIC study, a markedly higher proportion of pts in the CT arm than in the D arm received subsequent IO, which may have confounded the primary OS outcome. An exploratory analysis showed increased OS benefit with first-line D vs CT after adjusting for the effect of subsequent IO.

Editorial acknowledgement

Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Samantha Holmes, PhD, of Cirrus Communications (Macclesfield, UK), an Ashfield company, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca PLC.

Funding

AstraZeneca.

Disclosure

N. Reinmuth: Personal fees: BMS, Roche, AstraZeneca, Takeda, Novartis, Boehringer Ingelheim, MSD, Lilly, outside the conduct of the study. B.C. Cho: Grants/research support: Novartis, AstraZeneca, Yuhan, ONO/BMS, MSD, Bayer; Advisor/honoraria fees: AstraZeneca, Roche, Boehringer Ingelheim, Yuhan, BMS, MSD, Novartis; Speaker’s bureau fees: AZ, BMS, MSD, Novartis. J. Schneider: Stock/other ownership: AstraZeneca, Bristol-Myers Squibb, Pfizer, Celgene, Loxo; Consulting/advisory role: Takeda Oncology; Research funding: AstraZeneca, Bristol-Myers Squibb. F.A. Shepherd: Consultancy/advisory role: Lilly, AstraZeneca, Boehringer Ingelheim, Merck Serono; Stock ownership: Lilly, AstraZeneca; Honoraria: Lilly, AstraZeneca, BMS, Roche/Genentech, Merck Sharp & Dohme, Merck Serono, Boehringer Ingelheim; Research funding: Lilly, Pfizer, BMS, AstraZeneca, Roche Canada, Merrimack. S. Peters: Personal fees: AbbVie, Amgen, AZ, Bayer, Biocartis, BI, BMS, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche, Foundation Medicine, Illumina, Janssen, MSD, Merck Serono, Merrimack, Novartis, Pharma Mar, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda; Non-financial support: Amgen, AZ, BI, BMS, Clovis, F. Hoffmann-La Roche, Illumina, MSD, Merck Serono, Novartis, Pfizer. S.L. Geater: Research grants/funding: AstraZeneca, Roche, Novartis. T. Van Ngoc: Research funding: AstraZeneca, GSK, Novartis. M.C. Garassino: Personal fees: Eli Lilly, Boehringer Ingelheim, Otsuka Pharma, AstraZeneca, Novartis, BMS, Roche, Pfizer, Celgene, Incyte, Inivata, Takeda, Tiziana Science, Clovis, Merck Serono, Bayer, MSD, GSK. F. Liu, D. Clemett, P. Thiyagarajah, M. Ouwens, U. Scheuring: Full-time employment: AstraZeneca. N. Rizvi: Advisory boards: AbbVie, AZ, BMS, EMD Serono, Genentech, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Neogenomics, Oncomed, Gritstone, Bellicum; Equity: Oncomed, Gritstone, Bellicum, ARMO; Royalties: PGDX (patent filed by MSKCC). All other authors have declared no conflicts of interest.

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Proffered Paper session II Proffered Paper session

109O - Entrectinib in locally advanced or metastatic ROS1 fusion-positive non-small cell lung cancer (NSCLC): Integrated analysis of ALKA-372-001, STARTRK-1 and STARTRK-2

Presentation Number
109O
Lecture Time
09:39 - 09:51
Speakers
  • F. Barlesi (Marseille, CEDEX 20, France)
Location
Room A, Geneva Palexpo, Geneva, Switzerland
Date
Thu, 11.04.2019
Time
09:00 - 10:30
Authors
  • F. Barlesi (Marseille, CEDEX 20, France)
  • A. Drilon (New York, NY, United States of America)
  • F. De Braud (Milano, Italy)
  • B. Cho (Seoul, Korea, Republic of)
  • M. Ahn (Seoul, Korea, Republic of)
  • S. Siena (Milano, Italy)
  • M. Krebs (Manchester, United Kingdom)
  • C. Lin (Taipei, Taiwan)
  • T. John (Heidelberg, VIC, Australia)
  • D. Tan (Singapore, Singapore)
  • T. Seto (FUKUOKA, Fukuoka, Japan)
  • R. Dziadziuszko (Gdansk, Poland)
  • H. Arkenau (London, United Kingdom)
  • C. Rolfo (Baltimore, MD, United States of America)
  • J. Wolf (Cologne, Germany)
  • C. Ye (South San Francisco, United States of America)
  • T. Riehl (South San Francisco, United States of America)
  • S. Eng (South San Francisco, United States of America)
  • R. Doebele (Aurora, United States of America)

Abstract

Background

Entrectinib is a potent ROS1 inhibitor (as well as TRKA/B/C), designed to effectively penetrate the central nervous system (CNS); brain metastases are common in patients (pts) with advanced ROS1 fusion-positive NSCLC. Entrectinib achieves therapeutic levels in the CNS with antitumour activity in multiple intracranial tumour models. We present updated integrated safety and efficacy data from three Phase 1/2 entrectinib studies (ALKA-372-001 [EudraCT 2012-000148-88], STARTRK-1 [NCT02097810], STARTRK-2 [NCT02568267]) in pts with locally advanced/metastatic ROS1 fusion-positive NSCLC.

Methods

The analysis included pts with ROS1 inhibitor-naïve NSCLC harbouring a ROS1 fusion identified via nucleic acid-based diagnostic platforms. The ROS1 safety-evaluable population included pts who received ≥1 dose of entrectinib; the integrated efficacy analysis included pts with at least 6 months of follow-up. Tumour assessments were done at wk 4 and then every 8 wks by blinded independent central review (BICR), using RECIST v1.1. Primary endpoints by BICR: overall response rate (ORR), duration of response (DOR). Key secondary endpoints: progression-free survival (PFS), safety. Additional endpoints: intracranial ORR (complete/partial response), DOR in pts with intracranial response, PFS in pts with or without baseline CNS disease.

Results

In the ROS1 safety-evaluable population (n = 134), at least one treatment-related AE (TRAE) of any grade was seen in 93% of pts. Pts with at least one TRAE by highest grade were: grade 1/2, 59%; grade 3, 31%; grade 4, 4%. There were no grade 5 TRAEs. TRAEs led to dose reduction or discontinuation in 34% and 5% of pts, respectively. Efficacy outcomes are summarised in the table.

Conclusions

Entrectinib is highly active in pts with ROS1 fusion-positive NSCLC, including pts with CNS disease. Entrectinib is well tolerated with a manageable safety profile.

Clinical trial identification

ALKA-372-001 = EudraCT 2012-000148-88 – start date: 2015, trials ongoing STARTRK-1= NCT02097810 – start date: 2014, active, not recruiting (last update 2018) STARTRK-2 = NCT02568267 – start date: 2015, recruiting (last update 2018).

Editorial acknowledgement

Medical writing and editorial support provided by Charlotte Kennerley PhD of Gardiner-Caldwell Communications, Ashfield Healthcare Communications and was sponsored by Roche in accordance with Good Publication Practice guidelines.

Legal entity responsible for the study

F. Hoffmann-La Roche.

Funding

Ignyta, Inc., a wholly owned subsidiary of F. Hoffmann-La Roche Ltd.

Disclosure

F. Barlesi: Honoraria: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Clovis Oncology, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer, Takeda. A. Drilon: Advisory boards: Bayer, Ignyta, Loxo Oncology, Pfizer, Roche/Genentech, TP Therapeutics; Research funding: Loxo Oncology. F. De Braud: Advisory boards: Novartis, Roche/Genetech, Merk Serono, Bristol-Myers Squibb, GlaxoSmithKline, BMS, Celgene, Servier, Ignyta, Pfizer, MSD, Philogen, AstraZeneca, Boehringer Ingelheim, Sanofi Aventis, Giscad, Italfarmaco, Eli Lilly, Amgen, Nadirex. S. Siena: Advisory boards: Amgen, Bayer, BMS, CheckmAb, Celgene, Incyte, Merck, Novartis, Roche and Seattle Genetics. M.G. Krebs: Honoraria for Advisory boards: Roche, Janssen, Octimet, Achilles therapeutics; Travel grants: AstraZeneca. C.C. Lin: Honoraria: AstraZeneca, BeiGene, Daiichi Sankyo, Novartis, Roche; Advisory boards: Blueprint, Boehringer Ingelheim, Novartis. T. John: Advisory boards: BMS, AstraZeneca, Boehringer, Takeda, Pfizer, Novartis, Merck, Ignyta, Roche. D.S.W. Tan: Grants and honoraria for Advisory boards: Novartis, Bayer, Boehringer Ingelheim, Merck, AstraZeneca, BMS, Roche, Pfizer and grants from GSK, Novartis, AstraZeneca. T. Seto: Honoraria/research: Astellas, AZ, Bayer, BMS, Chugai, Daiichi Sankyo, Eisai, EliLilly, Kissei, Kyowa HakkoKirin, MerckSerono, Mochida, MSD, Nippon, Novartis, BI, NipponKayakuOno, Pfizer, Roche, Sanofi, ShowaYakuhinKako, Taiho, Takeda, YakultHonsha, Verastem. R. Dziadziuszko: Honoraria, consulting fees: Roche, Pfizer, Boehringer Ingelheim, Clovis Oncology, Novartis, AstraZeneca, Tesaro. H-T. Arkenau: Employee: HCA; Advisory boards: Beigene, Guardant Health, Bicycle. C. Rolfo: Honoraria, Advisory boards: Mylan, Novartis, MSD, GuardantHealth, AstraZeneca. J. Wolf: Corporate sponsored research: BMS, MSD, Novartis, Pfizer; Advisory boards: AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Ignyta, Lilly MSD, Novartis, Pfizer, Roche. C. Ye, T. Riehl, S. Eng: Employee: Genentech. R.C. Doebele: Research: Ignyta; Advisory boards; Roche, Ignyta, Takeda, AstraZeneca, Bayer; Stock ownership: Rain Therapeutics; Patent or biological material licensing fees: Ignyta, Abbott Molecular, Rain Therapeutics. All other authors have declared no conflicts of interest.

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ESMO-IASLC Best Abstracts Proffered Paper session

LBA3 - Efficacy and safety of first-line durvalumab (D) ± tremelimumab (T) vs platinum-based chemotherapy (CT) based on clinical characteristics in patients with metastatic (m) NSCLC: Results from MYSTIC

Presentation Number
LBA3
Lecture Time
15:00 - 15:15
Speakers
  • B. Cho (Seoul, Korea, Republic of)
Location
Room B, Geneva Palexpo, Geneva, Switzerland
Date
Thu, 11.04.2019
Time
14:45 - 16:15
Authors
  • B. Cho (Seoul, Korea, Republic of)
  • N. Reinmuth (Gauting, Germany)
  • K. Lee (Cheongju, Korea, Republic of)
  • M. Ahn (Seoul, Korea, Republic of)
  • A. Luft (Saint-Petersburg, Russian Federation)
  • M. Van den Heuvel (Amsterdam, Netherlands)
  • M. Cobo Dols (Málaga, Spain)
  • A. Smolin (Moscow, Russian Federation)
  • D. Vicente (Seville, Spain)
  • V. Moiseyenko (Saint-Petersburg, Russian Federation)
  • S. Antonia (Tampa, FL, United States of America)
  • S. Le Moulec (Paris, CEDEX 5, France)
  • G. Robinet (Brest, Cedex 2, France)
  • R. Natale (Los Angeles, United States of America)
  • E. Garon (Santa Monica, CA, United States of America)
  • K. Nakagawa (Osaka, Japan)
  • F. Liu (Gaithersburg, United States of America)
  • P. Thiyagarajah (Cambridge, United Kingdom)
  • S. Peters (Lausanne, Switzerland)
  • N. Rizvi (New York, United States of America)

Abstract

Background

In MYSTIC (NCT02453282), an open-label, Phase 3 trial of first-line D (anti-PD-L1) ± T (anti-CTLA-4) vs CT in mNSCLC, while not statistically significant, a clinically meaningful improvement in overall survival (OS) was seen with D vs CT in pts with tumour cell PD-L1 expression ≥25% (TC ≥25% [primary analysis population]; D vs CT, HR 0.76 [97.54% CI 0.56–1.02], p=0.036; D+T vs CT, HR 0.85 [98.77% CI 0.61–1.17], p=0.202). Here we report OS in clinically relevant pt subgroups and safety results from MYSTIC.

Methods

Immunotherapy/CT-naïve pts with mNSCLC were randomised (1:1:1) to D (20 mg/kg q4w); D (20 mg/kg q4w) + T (1 mg/kg q4w for 4 cycles); or CT. OS was analysed in pt subgroups based on baseline clinical characteristics in the PD-L1 TC ≥25% population (prespecified: age, gender, race, histology, smoking history and immune cell [IC] PD-L1 expression ≥25% vs <25%; post hoc: ECOG performance status). Safety (CTCAE v4.03) and tolerability were evaluated in all treated pts.

Results

The subgroup analysis included 488 pts (D, 163; D+T, 163; CT, 162). Baseline characteristics were balanced between treatment groups. Treatment with D±T resulted in numerical improvement in OS vs CT in most clinical subgroups. OS in pts aged ≥65 y, PD-L1 IC ≥25%, and performance status 0 showed a HR (95% CI) of 0.66 (0.45, 0.95), 0.63 (0.38, 1.04), and 0.54 (0.34, 0.84), respectively, with D vs CT and a HR (95% CI) of 0.72 (0.50, 1.02), 0.64 (0.39, 1.05), and 0.76 (0.50, 1.14) with D+T vs CT. Rates of TRAEs leading to discontinuation and imAEs were highest with D+T and rates of Grade ≥3 TRAEs were highest with CT (Table).

D (n=369)D+T (n=371)CT (n=352)
Any TRAE leading to discontinuation (PT), n (%)20 (5.4)49 (13.2)33 (9.4)
→Pneumonitis3 (0.8)7 (1.9)1 (0.3)
→Interstitial lung disease2 (0.5)5 (1.3)1 (0.3)
→Blood creatinine increased01 (0.3)4 (1.1)
→Colitis05 (1.3)0
→Diarrhoea04 (1.1)1 (0.3)
Any Grade ≥3 TRAE (PT), n (%)55 (14.9)85 (22.9)119 (33.8)
→Anaemia0036 (10.2)
→Neutropenia1 (0.3)035 (9.9)
→Fatigue6 (1.6)8 (2.2)7 (2.0)
→Thrombocytopenia0018 (5.1)
→Lipase increased3 (0.8)13 (3.5)1 (0.3)
Any imAE (grouped term), n (%)50 (13.6)105 (28.3)12 (3.4)
→Hypothyroidism21 (5.7)28 (7.5)2 (0.6)
→Pneumonitis8 (2.2)25 (6.7)5 (1.4)
→Diarrhoea7 (1.9)17 (4.6)1 (0.3)
→Rash5 (1.4)16 (4.3)2 (0.6)
→Colitis2 (0.5)12 (3.2)0

5 most common events in each category listed in descending order of frequency across the 3 treatment arms. PT, preferred term; TRAE, treatment-related AE; imAE, immune-mediated AE.

Conclusions

In MYSTIC, results of OS analyses across most pt subgroups showed favourable HRs for D±T vs CT, consistent with the overall primary analysis. The safety profile of D±T was manageable and consistent with previous studies with lower rates of Grade ≥3 TRAEs reported compared to CT.

Editorial acknowledgement

Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Samantha Holmes, PhD, of Cirrus Communications (Macclesfield, UK), an Ashfield company, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca PLC.

Funding

AstraZeneca.

Disclosure

B.C. Cho: Grants/research support: Novartis, AstraZeneca, Yuhan, ONO/BMS, MSD, Bayer; Advisor/honoraria fees: AstraZeneca, Roche, Boehringer Ingelheim, Yuhan, BMS, MSD, Novartis; Speaker’s bureau fees: AZ, BMS, MSD, Novartis. N. Reinmuth: Personal fees: BMS, Roche, AstraZeneca, Takeda, Novartis, Boehringer Ingelheim, MSD, Lilly, outside the conduct of the study. A. Smolin: Grants: AstraZeneca; Grants, personal fees: AstraZeneca, Roche, MSD, BMS; Personal fees: BIOCAD, Boehringer Ingelheim. S.J. Antonia: Advisory boards/contracted research: Novartis; Advisory boards: BMS, Merck, CBMG, Boehringer Ingelheim, AstraZeneca, Memgen, FLX Bio, Nektar, Venn. G. Robinet: Grants, personal fees: AstraZeneca, MSD; Personal fees: Boehringer Ingelheim. R. Natale: Spouse employed (Medical Science Liaison): AstraZeneca - However, her salary and compensation is completely unrelated to the contracted research work performed at my institution for which I am a co-investigator. E.B. Garon: Research funding: Merck, Genentech, AstraZeneca, Novartis, Lilly, BMS, Mirati Therapeutics, Dynavax, Iovance Biotherapeutics.  K. Nakagawa: Research funding: GlaxoSmithKline K.K., AstraZeneca K.K., Kyowa Hakko Kirin, Pfizer Japan Inc., AbbVie Inc., Novartis Pharma K.K., Nippon Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly Japan K.K., MSD K.K., Quintiles Inc., Ono Pharmaceutical, BMS, EPS International, Chugai Pharmaceutical, ICON Japan K.K., Gritstone Oncology, Inc., Linical, Yakult Honsha, PAREXEL International Corp., Otsuka Pharmaceutical, Astellas Pharma Inc., AC Medical Inc., Taiho Pharmaceutical, Merck Serono, EPS Associates, Quintiles Inc., Japan Clinical Research Operations, Eisai, PPD-SNBL K.K., Takeda Pharmaceutical, Covance Inc., inVentiv Health Japan, A2 Healthcare Corp., EP-CRSU; Honoraria: Astellas Pharma Inc., AstraZeneca K.K., Novartis Pharma K.K., Pfizer Japan Inc., Chugai Pharmaceutical, Ono Pharmaceutical, Nippon Boehringer Ingelheim, BMS, Kissei Pharmaceutical, Eli Lilly Japan K.K., MSD K.K., EPS Holdings Inc., Showa Yakuhin Kako, Clinical Trial, CareNet, Inc., Nikkei Business Publications, Inc., Nichi-Iko Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, AYUMI Pharmaceutical Corporation, Kyowa Hakko Kirin, Sym Bio Pharmaceuticals, Medicus Shuppan Publishers, Reno Medical K.K., Yodosha, Nanzando; Consulting or advisory role: Astellas Pharma Inc., Eli Lilly Japan K.K., Ono Pharmaceutical, Takeda Pharmaceutical. S. Peters: Personal fees: AbbVie, Amgen, AZ, Bayer, Biocartis, BI, BMS, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche, Foundation Medicine, Illumina, Janssen, MSD, Merck Serono, Merrimack, Novartis, Pharma Mar, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda; Non-financial support: Amgen, AZ, BI, BMS, Clovis, F. Hoffmann-La Roche, Illumina, MSD, Merck Serono, Novartis, Pfizer. F. Liu, P. Thiyagarajah: Full-time employment: AstraZeneca. N.A. Rizvi: Advisory boards: AbbVie, AZ, BMS, EMD Serono, Genentech, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Neogenomics, Oncomed, Gritstone, Bellicum; Equity: Oncomed, Gritstone, Bellicum, ARMO; Royalties: PGDX (patent filed by MSKCC).  All other authors have declared no conflicts of interest.

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