Abstract 1223P
Background
While 2nd- and 3rd-gen EGFR TKIs have shown clinical benefit vs 1st-gen EGFR TKIs in pts with EGFRm+ NSCLC, optimal sequence of treatment (tx) has yet to be defined. Overall survival (OS) is influenced by the availability/use of subsequent therapy after 1st-line tx. Emergence of T790M is the main mechanism of resistance to 2nd-gen EGFR TKIs and 2nd-line osi could be a tx option in this instance. A previous study (GioTag) showed median OS of >3 yrs in T790M+ pts treated with sequential afa/osi.
Methods
In this non-interventional, global study (NCT04179890), existing medical/electronic records were identified for consecutive EGFR TKI-naïve pts with EGFRm+ NSCLC (Del19 or L858R) treated with 1st-line afa/2nd-line osi in regular clinical practice (n = 191; all T790M+). Primary objective: time to tx failure (TTF). Key secondary objectives: OS and ORR.
Results
At the start of afa: median age (range) 62 yrs (34–88); female 55%; Asian 67%; ECOG PS (0/1/≥2) 31%/57%/12%; brain mets 14%; Del19/L858R 71%/29%. At the start of osi: ECOG PS (0/1/≥2) 25%/61%/14%; brain mets 14% (end of osi: 29%). Source of biopsy material (solid/liquid) 86%/3% at the start of afa; 54%/33% at the start of osi. Mutations were mainly detected with PCR methods (81%/86% at start of afa/osi). Overall, median TTF was 27.7 mos (afa 15.1 mos; osi 9.5 mos) and median OS was 36.5 mos. Median time from end of osi to death was 5.0 mos. ORR with afa and osi was 74% and 45%. TTF, OS and ORR were generally consistent across subgroups (Table). Table: 1223P
| Median TTF, mos (95% CI) | Median OS, mos (95% CI) | ORR, % afatinib | ORR, % osimertinib | |
| Overall | 27.7 (24.0–30.2) | 36.5 (32.9–41.8) | 74 | 45 |
| Del19 | 28.6 (24.5–31.2) | 38.0 (33.1–44.4) | 74 | 47 |
| L858R | 22.1 (19.8–30.4) | 33.1 (24.9–41.8) | 73 | 40 |
| Asian | 28.8 (22.4–31.2) | 42.3 (33.2–63.5) | 79 | 48 |
| Non-Asian | 25.5 (22.1–28.6) | 31.3 (27.2–38.0) | 67 | 36 |
| No brain metastases | 28.4 (24.3–30.8) | 37.6 (33.1–42.3) | 71 | 46 |
| Brain metastases | 21.4 (19.2–30.9) | 29.6 (22.4–NR) | 91 | 42 |
| ECOG PS <2 | 28.5 (24.0–30.9) | 39.8 (32.9–45.2) | 78 | 48 |
| ECOG PS ≥2 | 29.6 (20.5–32.3) | 33.1 (21.8–37.6) | 71 | 40 |
| Asian + Del19 | 29.7 (23.0–33.0) | 43.8 (33.2–71.1) | - | - |
Conclusions
These data support the previous GioTag study and show encouraging activity of sequential afa/osi in pts with EGFRm+ NSCLC and acquired T790M. Activity was highest in Asian pts with Del19 mutations but was observed across all subgroups including pts with poor ECOG PS or brain mets. ECOG PS and incidence of brain mets remained stable prior to, and after, afa tx.
Clinical trial identification
NCT04179890.
Editorial acknowledgement
Medical writing assistance, supported financially by Boehringer Ingelheim Pharmaceuticals Inc., was provided by Lynn Pritchard of Ashfield MedComms, an Ashfield Health Company.
Legal entity responsible for the study
Boehringer Ingelheim.
Funding
Boehringer Ingelheim.
Disclosure
S. Popat: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Beigene; Financial Interests, Personal, Advisory Board: Blueprint; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Guardant Health; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck KGaA; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Institutional, Other, Sub-investigator: Amgen; Financial Interests, Institutional, Other, Coordinating PI: ARIAD; Financial Interests, Institutional, Other, Local PI: AstraZeneca; Financial Interests, Institutional, Other, Coordinating PI: Boehringer Ingelheim; Financial Interests, Institutional, Other, Coordinating PI: Celgene; Financial Interests, Institutional, Other, Coordinating PI: Daiichi Sankyo; Financial Interests, Institutional, Other, Local PI: GlaxoSmithKline; Financial Interests, Institutional, Other, Sub-Investigator: MSD; Financial Interests, Institutional, Other, Local PI: Roche; Financial Interests, Institutional, Other, Coordinating PI: Takeda; Financial Interests, Institutional, Other, Local PI: Trizel; Financial Interests, Institutional, Other, Coordinating PI: Turning Point Therapeutics; Non-Financial Interests, Personal, Advisory Role, Honorary Clinical Advisor: ALK Positive UK; Non-Financial Interests, Personal, Leadership Role, Chair of Steering Committee: British Thoracic Oncology Group; Non-Financial Interests, Personal, Officer, Thoracic Faculty: European Society of Medical Oncology; Non-Financial Interests, Personal, Leadership Role, Foundation Council Member: European Thoracic Oncology Platform; Non-Financial Interests, Personal, Advisory Role, Communications Committee Member: International Association for the Study of Lung Cancer; Non-Financial Interests, Personal, Advisory Role, Scientific Advisory Board Member: Lung Cancer Europe; Non-Financial Interests, Personal, Member of the Board of Directors: Mesothelioma Applied Research Foundation; Non-Financial Interests, Personal, Advisory Role, Research Advisory Group Member: Ruth Strauss Foundation. M.J. Hochmair: Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria: Merck Sharp & Dohme; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Roche. C. Escriu: Financial Interests, Personal, Other, Consultant fees: Merck Sharp & Dohme; Financial Interests, Personal, Other, Consultant fee: Boehringer Ingelheim; Financial Interests, Personal, Other, Consultant fee: AstraZeneca; Financial Interests, Personal, Other, Lecture fee: Bristol Myers Squibb; Financial Interests, Personal, Other, Lecture fee: Pfizer. M.R. Migliorino: Financial Interests, Personal, Member of the Board of Directors: Boehringer Ingelheim; Financial Interests, Personal, Member of the Board of Directors: Roche; Financial Interests, Personal, Member of the Board of Directors: MSD; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Roche. N. Girard: Financial Interests, Personal, Full or part-time Employment, (Immediate family member): AstraZeneca; Financial Interests, Personal, Other, Consulting or advisory role: Roche; Financial Interests, Personal, Other, Consulting or advisory role: Lilly; Financial Interests, Personal, Other, Consulting or advisory role: Boehringer Ingelheim; Financial Interests, Personal, Other, Consulting or advisory role: AstraZeneca; Financial Interests, Personal, Other, Consulting or advisory role: Novartis; Financial Interests, Personal, Other, Consulting or advisory role: Pfizer; Financial Interests, Personal, Other, Consulting or advisory role: Bristol Myers Squibb; Financial Interests, Personal, Other, Consulting or advisory role: MSD; Financial Interests, Personal, Other, Consulting or advisory role: Takeda; Financial Interests, Personal, Other, Consulting or advisory role: GlaxoSmithKline; Financial Interests, Personal, Other, Consulting or advisory role: AbbVie; Financial Interests, Personal, Other, Consulting or advisory role: PharmaMar; Financial Interests, Personal, Other, Consulting or advisory role: Janssen; Financial Interests, Personal, Other, Consulting or advisory role: Sanofi; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Roche; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: MSD Oncology; Financial Interests, Institutional, Other, Research funding: Roche; Financial Interests, Institutional, Other, Research funding: AstraZeneca; Financial Interests, Institutional, Other, Research funding: Boehringer Ingelheim. H. Daoud: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim International GmbH. A. Märten: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim International GmbH. S. Miura: Financial Interests, Personal, Other, Speaker bureau fees/Expert testimony: Boehringer Ingelheim Inc.; Financial Interests, Personal, Other, Speaker bureau fees/Expert testimony: MSD Inc.; Financial Interests, Personal, Other, Speaker bureau fees/Expert testimony: Elli Lilly Japan; Financial Interests, Personal, Other, Speaker bureau fees/Expert testimony: Ono Pharma. Inc.; Financial Interests, Personal, Other, Speaker bureau fees/Expert testimony: Chugai Pharm Inc. All other authors have declared no conflicts of interest.