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Afatinib in EGFR TKI-naïve patients with · PDF file Afatinib in EGFR TKI-naïve patients with EGFR-mutation positive NSCLC: interim analysis from a Phase IIIb, open-label study Filippo

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  • Afatinib in EGFR TKI-naïve patients with EGFR-mutation positive NSCLC:

    interim analysis from a Phase IIIb, open-label study

    Filippo de Marinis,1 Konstantin K Laktionov,2 Artem Poltoratskiy,3 Inna Egorova,4

    Maximilian Hochmair,5 Antonio Passaro,1 Maria Rita Migliorino,6 Giulio Metro,7 Maya Gottfried,8 Daphne Tsoi,9 Gyula Ostoros,10 Simona Rizzato,11 Guzel Z Mukhametshina,12

    Michael Schumacher,13 Silvia Novello,14 Rafal Dziadziuszko,15 Wenbo Tang,16

    Laura Clementi,17 Agnieszka Cseh,18 Dariusz Kowalski19

    Presented by: Zhiyi Xue20

    1European Institute of Oncology, Milan, Italy; 2Russian Academy of Medical Sciences, Moscow, Russia; 3Petrov Research Institute of

    Oncology, St Petersburg, Russia; 4Clinical Oncology Dispensary, St Petersburg, Russia; 5Otto Wagner Hospital, Vienna, Austria; 6San

    Camillo-Forlanini Hospital, Rome, Italy; 7Santa Maria della Misericordia Hospital, Perugia, Italy; 8Tel Aviv University, Tel Aviv, Israel; 9St

    John of God Murdoch Hospital, Murdoch, WA, Australia; 10National Korányi Institute for Pulmonology, Budapest, Hungary; 11Azienda

    Sanitaria-Universitaria Integrata, Udine, Italy; 12Ministry of Health of the Republic of Tatarstan, Kazan, Russia; 13Ordensklinikum

    Elisabethinen, Linz, Austria; 14Department of Oncology, University of Turin, AOU San Luigi, Orbassano, Italy; 15Medical University of

    Gdansk, Gdansk, Poland; 16Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA; 17Boehringer Ingelheim Italia S.p.A.,

    Milan, Italy; 18Boehringer Ingelheim RCV GmbH & Co. KG, Vienna, Austria; 19Oncology Centre and Institute, Warsaw, Poland; 20Boehringer Ingelheim (China) Investment Co.,Ltd.

  • • We thank all patients and their families, and investigators and staff at all clinical sites, for their valuable participation in this study

    • This study was funded by Boehringer Ingelheim

    • Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Hannah Simmons, of GeoMed, an Ashfield company, part of UDG Healthcare plc, during the development of this slide deck

    Acknowledgements and Disclosures

  • Background

    EGFRm+, EGFR mutation-positive; HR, hazard ratio; PFS, progression-free survival; RCT, randomized controlled trial

    1. Sequist LV, et al. J Clin Oncol 2013;31:3327–34; 2. Wu Y-L, et al. Lancet Oncol 2014;15:213–22; 3. U.S. Food and Drug Administration. GILOTRIF® (afatinib). Highlights of Prescribing Information.

    Accessed 9 August 2019; 4. European Medicines Agency. GIOTRIF® (afatinib). Summary of Product Characteristics. Accessed 9 August 2019; 5. Wu Y-L, et al. Ann Oncol 2019;30:171–210

    RCTs are conducted in highly controlled settings, with strict inclusion criteria; therefore, it is important to support findings of afatinib efficacy and tolerability with real-world studies of broader

    patient populations

    These findings led to the approval of afatinib in China and several other countries for the first-line

    treatment of patients with EGFRm+ NSCLC3–5

    LUX-Lung 3 (Global) and 6 (China/South Korea/Thailand)

    Median PFS with afatinib vs chemotherapy in patients with EGFRm+ NSCLC harboring common/uncommon mutations:

    • LUX-Lung 3: 11.1 vs 6.9 months, HR=0.58; p=0.0011

    • LUX Lung 6: 11.0 vs 5.6 months, HR=0.28; p

  • • Patients with locally advanced/metastatic EGFRm+ NSCLC

    • EGFR TKI-naïve

    • ECOG PS 02

    • Patients with asymptomatic brain metastases permitted*

    Interim Analysis of a Prospective, Open-label, Multicenter, Phase IIIb Trial (NCT01853826)

    *Previously treated, with SD for ≥4 weeks on stable doses of medication; †All patients who received at least one dose of afatinib (treated set) were included in the safety and efficacy analyses; ‡AEs were recorded at baseline and then every 28 days during treatment. Physical examinations and disease assessments were performed at the same time points; AE, adverse event; DCR, disease control rate; ECOG PS, Eastern Cooperative Oncology Group performance status; ORR, objective response rate; SD, stable disease; TKI, tyrosine kinase inhibitor; TTSP, time to symptomatic progression

    Afatinib 40 mg/day until disease progression or other withdrawal criteria were met

    Primary endpoint:† Safety (AEs in descriptive fashion)‡

    Further endpoints: PFS, TTSP, ORR, DCR

    Dose reduction to 30 or 20 mg/day was permitted based on individual tolerability

  • • 479 patients were enrolled and treated, including patients who are sometimes not eligible for RCTs1–3

    Patient Disposition and Baseline Characteristics

    *Missing (n=1); †Del19 or L858R mutations only (i.e., no uncommon mutations); ‡Uncommon EGFR mutations with/without common mutations; §Patients can appear in more than one mutation category; ¶ Percentage in relation to the number of patients in the uncommon cohort; Data cut-off: 30 April 2018

    1. Sequist LV, et al. J Clin Oncol 2013;31:3327–34; 2. Wu Y-L, et al. Lancet Oncol 2014;15:213–22;

    3. Park K, et al. Lancet Oncol 2016;17:577–89

    Uncommon mutation§

    n (%)¶

    ex20ins 37 (44)

    G719S/A/C 12 (14)

    T790M 12 (14)

    L861Q 10 (12)

    S768I 9 (11)

    Other 18 (21)

    2nd

    81 (17%)

    1st

    374 (78%)

    Line of therapy

    ≥3rd

    24 (5%)

    0 171 (36%)

    1 271 (57%)

    ECOG PS*

    2 36 (8%)

    Other 14 (3%)

    Caucasian 465 (97%)

    Race

    Male 165 (34%)

    Female 314 (66%)

    Gender

    No 395 (83%)

    Yes 83 (17%)

    Baseline brain metastases*

    Uncommon‡

    84 (18%)

    EGFR mutation type*

    Del19†

    232 (48%)

    L858R†

    162 (34%)

  • PFS and TTSP

    *Missing n=1; †Del19 or L858R mutations only (i.e., no uncommon mutations); ‡Uncommon EGFR mutations with/without common mutations; CI, confidence interval

    0

    0.0

    6 12 18

    E s tim

    a te

    d p

    ro b a b ili

    ty

    0.2

    0.4

    0.6

    0.8

    1.0

    24 30 36 42 48 54

    Time (months) Number at risk

    479 332 237 167 113 72 55 41 21 2TTSP

    n

    PFS TTSP

    Median, months (95% CI)

    13.4 (11.8–14.5)

    14.9 (13.8–17.6)

    10.1

    13.9

    6.0

    13.1

    15.9

    6.2

    12.9

    15.4

    6.6

    13.2

    13.8

    13.4

    13.7

    15.8

    7.4

    14.5

    19.3

    8.9

    14.7

    17.2

    8.1

    14.7

    15.6

    14.9

    0 5 10 15 20

    Time from start of afatinib (months)

    479Overall population

    395No

    83Yes

    3741st

    812nd

    24≥3rd

    1710

    362

    232Del19†

    162

    Uncommon‡

    Brain metastases*

    Line of therapy

    ECOG PS*

    EGFR mutation type*

    Median PFS

    84

    L858R†

    1 271

    Median TTSP

    479 332 229 151 98 67 51 36 16 1PFS

  • AEs were Predictable and Manageable

    *DR SAEs, n=39 (8%), most commonly diarrhea, n=15 (3%), dehydration, n=6 (1%), vomiting, n=5 (1%), all others n

  • • Interim efficacy and safety results of this prospective study of afatinib in a near ‘real-world’ patient population with EGFRm+ NSCLC were consistent with findings from the pivotal LUX-Lung trials1–3

    • Efficacy findings were encouraging, with an overall median PFS and TTSP of 13.4 and 14.9 months, respectively

    – Prolonged efficacy was seen in patients with Del19 EGFRm+ disease (median PFS 15.9 months; TTSP 19.3 months)

    • Activity of afatinib was also confirmed in patients who are sometimes excluded from RCTs

    – Asymptomatic brain metastases (median PFS 10.1 months; TTSP 13.7 months)

    – ECOG PS 2 (median PFS 6.2 months; TTSP 8.9 months)

    – One/two prior lines of therapy (median PFS 13.2/6.6 months; TTSP 14.7/8.1 months)

    • Diarrhea (87%) and rash (51%) were the most common DRAEs. Both were generally manageable with dose reduction, and led to few treatment discontinuations (3% and 1%, respectively)

    Conclusions

    1. Sequist LV, et al. J Clin Oncol 2013;31:3327–34 2. Wu Y-L, et al. Lancet Oncol 2014;15:213–22 3. Park K, et al. Lancet Oncol 2016;17:577–89

  • Online Resources

    *These materials are for personal use only and may not be produced without written permission of the authors and the appropriate copyright permissions

    Scan the QR code, or follow the URL, for an electronic copy of the slides and supplementary content*

    http://tqr.bz/4nk

  • ORR and DCR

    ORR 46% (n=218)

    Best tumor response (N=479) n (%)

    CR 25 (5)

    PR 193 (40)

    SD 193 (40)

    PD 34 (7)

    NE 23 (5)

    CR, complete response; NE, non-evaluable; PD, progressive disease; PR, partial response

    DCR 86% (n=411)

  • Any-cause AEs

    All grades, n (%)

    Grade ≥3, n (%)

    Any AE 478 (>99) 315 (66)

    Any SAE 202 (42) 171 (36)

    Any-cause AEs in ≥10% of patients

    Diarrhea 422 (88) 80 (17)

    Rash 250 (52) 51 (11)

    Paronychia 155 (32) 18 (4)

    Asthenia 116 (24) 25 (5)

    Mucosal inflammation 93 (19) 13 (3)

    Dry skin 85 (18) 1 (