1206P - UNcommon EGFR mutations: International Case series on efficacy of Osimertinib in Real-life practice in first-liNe setting (UNICORN)

Background

About 10% of EGFR mutations (EGFRmut) are ‘uncommon mutations’ (ucEGFRmut), correlating with lower response to 1^st & 2^nd generation EGFR inhibitors (EGFRi) compared to common mutations. Osimertinib is a 3^rd generation EGFRi, active against common EGFRmut. Efficacy data of osimertinib in ucEGFRmut are scarce. We aimed to collect real-world data of the usage of osimertinib as the 1st EGFRi for ucEGFRmut.

Methods

This is a multi-center, international, academic-initiated retrospective study of mNSCLC with ucEGFRmut treated with osimertinib prior to any other EGFRi. RECIST response was evaluated by investigators. PFS and OS were calculated by Kaplan-Meier method from initiation of Osimertinib, duration of response (DOR) was calculated for responders.

Results

46 patients were identified in 18 centers from 8 countries (Austria, Belgium, France, Germany, Italy, Israel, Spain, Switzerland). Median age was 64 (range 37-91) years, 72% females, 89% Caucasian, never/former/current smokers were 50%/33%/15% respectively, ECOG PS was 0-1/2/3-4 in 78%/13%/6.5%. G719X was the most frequent mutation (16 pts, 34.8%), followed by de novo T790M (9 pts, 22%, 5 of them compound with common mutations) and L861Q (7 pts, 15.2%). Compound EGFR mutations were found in 16 pts (34.8%), TP53 mutations in 13 pts (28.3%). Most frequent metastatic sites were brain/bone/lung in 47%/47%/36% respectively. For 37 pts (80.4%), osimertinib was the 1^st treatment given for advanced disease. Most frequent toxicities were gastrointestinal (24 pts, 52%) and skin (16 pts, 35%); 5 patients had grade 3-4 AEs. RECIST response (RR) was available for 44 pts, CR for 2 (4.5%), PR for 20 (45.5%), SD for 17 (38.6%), and PD for 5 (11.4%). Median DOR was 17.4 months (95% CI 9.1-NA). RR for G719X was 43.8%, 33.3% for T790M, and 71.4% for L861Q. Median PFS was 9.1 months (95% CI 8.1–19.2). Median OS was 18.4 months (95% CI 13.5-NR).

Conclusions

Osimertinib showed activity in ucEGFRmut with 85% disease control rate and encouraging PFS and DOR. This report comprises, to the best of our knowledge, the largest dataset of osimertinib as the first EGFRi for ucEGFRmut. UNICORN continues to recruit patients, to expand our knowledge on efficacy of osimertinib for these patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

AstraZeneca.

Disclosure

J. Bar: Financial Interests, Personal, Advisory Board, MSD; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Causalis; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Takeda; Financial Interests, Institutional, Invited Speaker: AbbVie; Financial Interests, Institutional, Other, local sub-investigator: Novartis; Financial Interests, Institutional, Research Grant: OncoHost; Financial Interests, Institutional, Research Grant: ImmuneAI; Financial Interests, Institutional, Invited Speaker: AstraZeneca. M. Wolner: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Other, grant: Roche; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Institutional, Other, Community Relations: Merck Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: AstraZeneca. N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Sivan; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Advisory Board: Grunenthal; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Institutional, Research Grant, Local: Roche; Financial Interests, Institutional, Research Grant, Local: Sivan; Financial Interests, Institutional, Research Grant, Local: Janssen; Non-Financial Interests, Invited Speaker, French Thoracic Cancer Intergroup, Treasurer: IFCT; Non-Financial Interests, Officer, International Thymic Malignancy Interest Group, President: ITMIG; Other, Other, My partner is an employee: AstraZeneca. Y. Rottenberg: Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: AZD; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Medison; Financial Interests, Institutional, Invited Speaker: CannbioRx; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: AZD. E. Dudnik: Financial Interests, Personal, Invited Speaker: BMS, MSD, AstraZeneca, Roche, Takeda, Pfizer, Novartis, Sanofi; Financial Interests, Personal, Advisory Board: Takeda, Sanofi, BMS; Non-Financial Interests, Member: EORTC; Non-Financial Interests, Member: IASLC; Non-Financial Interests, Leadership Role: ILCG. M.J. Hochmair: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Lilly. K. Cuppens: Financial Interests, Personal, Advisory Board: F. Hoffmann-La Roche; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Expert Testimony: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Expert Testimony: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim. M. Reck: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Board: Mirati; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Samsung Bioepis. A. Calles Blanco: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Institutional, Research Grant, Drug-only for Investigator-initiated trial: Merck Sharp & Dohme. S. Häfliger: Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Institutional, Advisory Board: Eli Lily; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Novartis. N. Peled: Financial Interests, Personal, Advisory Board, honorarium for advisory board and research grant: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Foundation Medicine, Gaurdant360, Merck, MSD, Novartis, NovellusDx, Pfizer, Roche, Takeda; Financial Interests, Institutional, Research Grant, research grants: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Foundation Medicine, Gaurdant360, Merck, MSD, Novartis, NovellusDx, Pfizer, Roche, Takeda; Non-Financial Interests, Principal Investigator, Research: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Foundation Medicine, Gaurdant360, Merck, MSD, Novartis, NovellusDx, Pfizer, Roche, Takeda. A. Addeo: Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Advisory Board: AZD; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Advisory Board: Eli Lilly. All other authors have declared no conflicts of interest.