1217P - EGFR TKIs in patients (pts) with NSCLC with uncommon EGFR mutations: A real-world cohort study (UpSwinG)

Background

Despite being an established treatment (tx) option in pts with EGFR mutation-positive NSCLC with common mutations (Del19 or L858R), limited data exist for EGFR TKI tx in the 7–23% of pts with uncommon EGFR mutations.

Methods

In this non-interventional, global study (NCT04179890), existing medical/electronic records were searched for consecutive EGFR TKI-naïve (at diagnosis) pts with uncommon EGFR mutations (major uncommon [G719X, L861Q or S768I], compound, ‘other’, ex20ins), treated with erlotinib, gefitinib, afatinib, osimertinib (1^st- or 2^nd-line). Endpoints were time to tx failure (TTF), ORR, OS, and duration of response (DoR).

Results

Pts (n=246; median age: 69.5 years; female: 56%; Asian: 90%; brain metastases: 8%; ECOG PS ≥2: 16%) were recruited from 36 sites in 9 countries. Most pts (n=226, 92%) received EGFR TKIs as 1^st-line tx (afatinib: n=126, 56%; 1^st-gen EGFR TKI: n=93, 41%; osimertinib: n=5, 2%; combination: n=2, 1%). EGFR TKIs received as 2^nd-line tx (n=52) were: afatinib (n=11, 21%), 1^st-gen EGFR TKIs (n=20, 38%) and osimertinib (n=21, 40%). Median duration of 1^st-line EGFR TKI tx was 10.4 mos. From the start of 1^st- to the start of 2^nd-line tx, ECOG PS was stable/improved/deteriorated in 73/9/18% of pts. Overall, median TTF, OS, and DoR with EGFR TKIs was 9.9, 24.4 and 10.0 mos, and ORR was 43%. Strongest responses were seen in pts with major uncommon and/or compound mutations (Table). In the major uncommon group, median TTF and OS in pts with brain metastases was 17.3 and 33.9 mos, and with ECOG PS ≥2 was 8.6 and 14.3 mos.

Conclusions

In a real-world setting, EGFR TKIs were the tx of choice in pts with uncommon EGFR mutations. ECOG PS remained stable in pts from 1^st- to 2^nd-line tx. Activity was highest in compound and major uncommon groups (including pts with poor risk factors). Some pts in the highly heterogeneous ‘other’ and ex20ins groups responded to EGFR TKIs, demonstrating the need for precise information on EGFR mutation type. Table: 1217P

Clinical trial identification

NCT04179890.

Editorial acknowledgement

Medical writing assistance, supported financially by Boehringer Ingelheim Pharmaceuticals Inc., was provided by Steven Kirkham of Ashfield MedComms, an Ashfield Health Company, during the preparation of this abstract.

Legal entity responsible for the study

Boehringer Ingelheim.

Funding

Boehringer Ingelheim.

Disclosure

S. Miura: Financial Interests, Personal, Speaker’s Bureau, Speaker bureau fees/Expert testimony: Boehringer Ingelheim Inc.; Financial Interests, Personal, Speaker’s Bureau, Speaker bureau fees/Expert testimony: MSD Inc.; Financial Interests, Personal, Speaker’s Bureau, Speaker bureau fees/Expert testimony: Elli Lilly Japan; Financial Interests, Personal, Speaker’s Bureau, Speaker bureau fees/Expert testimony: Ono Pharma. Inc.; Financial Interests, Personal, Speaker’s Bureau, Speaker bureau fees/Expert testimony: Chugai Pharm Inc. J. Shih: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Eli Lilly; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role: Chugai Pharma; Financial Interests, Personal, Advisory Role: Ono Pharmaceutical; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: CStone Pharmaceuticals; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria: Eli Lilly; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Merck Sharp & Dohme; Financial Interests, Personal, Other, Honoraria: Chugai Pharma; Financial Interests, Personal, Other, Honoraria: Ono Pharmaceutical; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb. T. Okamoto: Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Eli Lilly Japan; Financial Interests, Personal, Other, Honoraria: Johnson & Johnson; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: Nippon Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria: Taiho Pharmaceutical; Financial Interests, Institutional, Other, Research funding: Chugai Pharmaceutical; Financial Interests, Institutional, Other, Research funding: Covidien Japan; Financial Interests, Institutional, Other, Research funding: Eli Lilly Japan; Financial Interests, Institutional, Other, Research: MSD; Financial Interests, Institutional, Other, Research: Nippon Boehringer Ingelheim; Financial Interests, Institutional, Other, Research: Novartis Pharma; Financial Interests, Institutional, Other, Research: Ono Pharmaceutical; Financial Interests, Institutional, Other, Research: Pfizer Japan; Financial Interests, Institutional, Other, Research: Taiho Pharmaceutical. H.K. Ahn: Financial Interests, Personal, Other, Speaker bureau fees and Expert testimony: AstraZeneca; Financial Interests, Personal, Other, Speaker bureau fees and Expert testimony: Roche; Financial Interests, Personal, Other, Speaker bureau fees and Expert testimony: Lilly. Y. Sato: Financial Interests, Personal, Other, Honoraria: Chugai Pharma; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: Ono Pharmaceutical Co.; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Taiho Pharmaceutical; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Nippon Kayaku. C. Mascaux: Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Kephren; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Kephren; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, travel, accommodations, expenses: Roche; Financial Interests, Personal, Other, travel, accommodations, expenses: AstraZeneca; Financial Interests, Personal, Other, travel, accommodations, expenses: Boehringer Ingelheim; Financial Interests, Personal, Other, travel, accommodations, expenses: Takeda. 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. 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. All other authors have declared no conflicts of interest.