1212P - Afatinib for the treatment of NSCLC with uncommon EGFR mutations: An updated database of 1023 cases

Background

Optimal treatment (tx) of patients (pts) with NSCLC and uncommon EGFR mutations (non Del19/L858R) remains unclear due to limited clinical data. We previously developed a database of 693 pts with NSCLC and uncommon EGFR mutations treated with afatinib (afa) in RCTs and real-world practice. Here, we provide an update of >1000 pts, with more data on specific mutations.

Methods

Pts were identified from a prospective database developed by Boehringer Ingelheim and published cases. Pts were categorised as T790M+, ex20ins, major uncommon (G719X, L861Q, S768I) and ‘other’ mutations. Pts with compound mutations (≥2 any/≥1 uncommon EGFR mutations) were also analysed. Key endpoints were time to tx failure (TTF) and ORR (mostly based on investigator review).

Results

1023 pts were identified: EGFR TKI naïve/pretreated/unknown n = 587/425/11. Most pts were treated in clinical studies/compassionate use programmes. Demographics (TKI naïve/pretreated): Asian 63/46%; ≥75 yrs 20/11%; female 53/64%, confirmed brain mets 12/6%. Mutation categories (TKI naïve/pretreated): T790M+ 10/35%; ex20ins 23/20%; major 52/28%; other 15/18% (including E709X 3/3%, L747X 3/<1%); compound 31/49%. Overall, median TTF (TKI naïve/pretreated): 10.7/4.5 mos. Median TTF (TKI naïve) in Asians/non-Asians and pts with brain mets: 11.5/10.3 and 8.2 mos. ORR (TKI naïve) in major uncommon, compound and other mutations was 59/64/64%. The table shows TTF and ORR (TKI naïve) by mutation category. Few ex20ins were fully described, but notable activity was seen against some subtypes such as A763, M766, N771, V769. 15 pts with known acquired EGFR resistance mutations to osimertinib (osi; G724S, L718X, C797S) were given afa post osi: ORR: 36%.

Conclusions

Afa showed activity against major uncommon, compound, other (including E709X and L747X) and some specific ex20ins mutations. The data support the use of afa in these settings. Moderate activity was seen post-osi. Table: 1212P

Clinical trial identification

N/A

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

J.Y.C. Yang: Financial Interests, Personal, Other: Boehringer Ingelheim; Financial Interests, Personal, Other: Eli Lilly; Financial Interests, Personal, Other: Roche/Genentech; Financial Interests, Personal, Other: Chugai; Financial Interests, Personal, Other: Astellas; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: Merck Serono; Financial Interests, Personal, Other: Pfizer; Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other: Celgene; Financial Interests, Personal, Other: Merrimack; Financial Interests, Personal, Other: Yuhan Pharmaceuticals; Financial Interests, Personal, Other: Bristol Myers Squibb; Financial Interests, Personal, Other: Ono Pharmaceutical; Financial Interests, Personal, Other: Daiichi Sankyo; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Hansoh Pharmaceuticals; Financial Interests, Personal, Other: Takeda Pharmaceuticals. M. Schuler: Financial Interests, Personal, Other, Consultant: AstraZeneca; Financial Interests, Personal, Other, Consultant and received honoraria for CME presentations: Boehringer Ingelheim; Financial Interests, Personal, Other, Consultant and received honoraria for CME presentations: Bristol Myers Squibb; Financial Interests, Personal, Other, Consultant: GlaxoSmithKline; Financial Interests, Personal, Other, Consultant and received honoraria for CME presentations: Janssen; Financial Interests, Personal, Other, Consultant: MorphoSys; Financial Interests, Personal, Other, Consultant and received honoraria for CME presentations: Novartis; Financial Interests, Personal, Other, Consultant: Roche; Financial Interests, Personal, Other, Consultant: Takeda; Financial Interests, Personal, Other, Honoraria for CME presentation: Amgen; Financial Interests, Personal, Other, Honoraria for CME presentation: MSD; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb. 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: Bristol Myers Squibb; 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, Principal Investigator, Coordinating PI: ARIAD; Financial Interests, Institutional, Principal Investigator, Local PI: AstraZeneca; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Boehringer Ingelheim; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Celgene; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Daiichi Sankyo; Financial Interests, Institutional, Principal Investigator, Local PI: GlaxoSmithKline; Financial Interests, Institutional, Other, Sub-investigator: MSD; Financial Interests, Institutional, Principal Investigator, Local PI: Roche; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Takeda; Financial Interests, Institutional, Principal Investigator, Local PI: Trizel; Financial Interests, Institutional, Principal Investigator, 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. S. Miura: Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: MSD Inc.; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly Japan; Financial Interests, Personal, Speaker’s Bureau: Ono Pharma Inc.; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharma Inc.; Financial Interests, Personal, Expert Testimony: Boehringer Ingelheim; Financial Interests, Personal, Expert Testimony: MSD Inc.; Financial Interests, Personal, Expert Testimony: Eli Lilly Japan; Financial Interests, Personal, Expert Testimony: Ono Pharma Inc.; Financial Interests, Personal, Expert Testimony: Chugai Pharma Inc. K. Park: Financial Interests, Personal, Other, consultancy: Boehringer Ingelheim; Financial Interests, Personal, Other, consultancy: Amgen; Financial Interests, Personal, Other, consultancy: AbbVie; Financial Interests, Personal, Other, consultancy: AstraZeneca; Financial Interests, Personal, Other, consultancy: Bristol Myers Squibb; Financial Interests, Personal, Other, consultancy: Daiichi Sankyo; Financial Interests, Personal, Other, consultancy: Eli Lilly; Financial Interests, Personal, Other, consultancy: Hanmi; Financial Interests, Personal, Other, consultancy: Johnson & Johnson; Financial Interests, Personal, Other, consultancy: MSD; Financial Interests, Personal, Other, consultancy: Merck KGaA; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Member, Data Monitoring Committee Member: Incyte; Financial Interests, Personal, Member, Data Monitoring Committee Member: BeiGene. A. Passaro: Financial Interests, Personal, Other, received honoraria for consulting, advisory role or lectures: AstraZeneca; Financial Interests, Personal, Other, received honoraria for consulting, advisory role or lectures: Agilent/Dako; Financial Interests, Personal, Other, received honoraria for consulting, advisory role or lectures: Boehringer Ingelheim; Financial Interests, Personal, Other, received honoraria for consulting, advisory role or lectures: Bristol Myers Squibb; Financial Interests, Personal, Other, received honoraria for consulting, advisory role or lectures: Eli Lilly; Financial Interests, Personal, Other, received honoraria for consulting, advisory role or lectures: Janssen; Financial Interests, Personal, Other, received honoraria for consulting, advisory role or lectures: Merck Sharp & Dohme; Financial Interests, Personal, Other, received honoraria for consulting, advisory role or lectures: Pfizer; Financial Interests, Personal, Other, received honoraria for consulting, advisory role or lectures: Roche/Genentech; Financial Interests, Personal, Other, received honoraria for consulting, advisory role or lectures: Novartis. F. de Marinis: Financial Interests, Personal, Other, Honoraria or consulting fees: AstraZeneca; Financial Interests, Personal, Other, Honoraria or consulting fees: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria or consulting fees: Merck Sharp & Dohme; Financial Interests, Personal, Other, Honoraria or consulting fees: Roche. F. Solca: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. A. Märten: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. E.S. Kim: Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Speaker’s Bureau: Takeda; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Other, advisory board/consultancy: Merck; Financial Interests, Personal, Other, advisory board/consultancy: Takeda; Financial Interests, Personal, Other, advisory board/consultancy: Roche; Financial Interests, Personal, Other, advisory board/consultancy: Boehringer Ingelheim; Financial Interests, Personal, Other, advisory board/consultancy: AstraZeneca; Financial Interests, Personal, Other, advisory board/consultancy: Pfizer; Financial Interests, Personal, Other, honorarium from promotional activities: Merck; Financial Interests, Personal, Other, honorarium from promotional activities: Takeda; Financial Interests, Personal, Other, honorarium from promotional activities: Roche; Financial Interests, Personal, Other, honorarium from promotional activities: Boehringer Ingelheim; Financial Interests, Personal, Other, honorarium from promotional activities: AstraZeneca; Financial Interests, Personal, Other, honorarium from promotional activities: Pfizer; Financial Interests, Personal, Other, fees for travel/accommodation/expenses: Merck; Financial Interests, Personal, Other, fees for travel/accommodation/expenses: Takeda; Financial Interests, Personal, Other, fees for travel/accommodation/expenses: Roche; Financial Interests, Personal, Other, fees for travel/accommodation/expenses: Boehringer Ingelheim; Financial Interests, Personal, Other, fees for travel/accommodation/expenses: AstraZeneca; Financial Interests, Personal, Other, fees for travel/accommodation/expenses: Pfizer.