Abstract 996P
Background
In 10-20% of patients (pts) with EGFR mutated NSCLC, an assorted group of uncommon mutations can be detected. These mutations confer variable sensitivity to 1st and 2nd generation TKIs, overall resulting in lower therapeutic activity. Data of Osimertinib (Osi), a 3rd generation TKI, are limited and strongly warranted.
Methods
This is a retrospective multicenter study of pts with advanced NSCLC with any uncommon EGFR alteration and treated with Osi since August 2017. Investigators collected response in terms of overall response rate (ORR) and disease control rate (DCR) by RECIST 1.1 criteria. Survival outcomes were estimated by Kaplan-Meier method.
Results
As of April, 2022, 65 pts were identified in 18 institutions in Italy. Pts characteristics: 62% female, median age 68 (31-87) years, 86% ECOG PS 0-1, 63% smoking history, 92% caucasian, 95% adenocarcinoma. A large group of pts presented compound mutations (37%, N=24) (Table). In 88% (N=57) Osi was used in TKI-naïve setting and in 80% as first treatment. ORR and DCR were 45% (CI 95%, 32-58%) and 78% (CI 95%, 66-88%) in the evaluable population (N=60), and 49% (CI 95%, 34-64%) and 78% (CI 95%, 63-88%) in TKI-naïve (excluded ins20) cohort (N=49), respectively. With a median time of follow up of 13 months, median PFS and DOR in TKI-naïve were 11 months (CI 95%, 7-18) and not reached (CI 95%,11-n.r.), respectively. Table: 996P
EGFR mutations and outcome in ARTICUNO study.
| Major uncommon mutation (single or compound*) | N (%) | ORR% (95%CI), DCR% (95%CI), mPFS (months, 95%CI) |
| G719X | 19 (29) | 50 [26-74],89 [65-99],11 [5-15] |
| L861X | 15 (23) | 50 [23-77],86 [57-98],9 [5-14] |
| S768I | 11 (17) | 55 [23-83],91 [59-100],17 [7-24] |
| OTHERS (minor mutations or Ins20) | 27 (42%) | Best Response |
| L858R+dnT790M (N=2), L833V+L858R, Del19+L747Q, I740_K745dup, V738_I744ins,EGFR-KDD, D770_N771insSVD | 8 (12) | CR/PR |
| V738_A743del, Del19+A750P, Del19+S751V, Del19+P753S+aqT790M, Del19+L858R, V769_D770insASV, A767_V769dup | 7 (11) | SD |
| Y801C, R831C, A702S, V765M, A702_K728del, G709T, E709_T710delinsD (N=2), D770_N771insSVD, A767_V769dup | 10 (15) | PD |
| E868Q, V769_D770insASV | 2 (3) | NE |
∗In cases of combination of 2 uncommon major mutations, the patient case is re-counted for each major mutation
Conclusions
In this widest known dataset, major uncommon mutations were the most frequent, largely occurring as compound. Notably, one third of our cases presented heterogeneous minor uncommon mutations. Osimertinib showed relevant activity, overall comparable with data of Afatinib and Osi in a Korean trial. ARTICUNO study is still ongoing and more data will be presented.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Oncologia Falck, Grande Ospedale Metropolitano Niguarda, Milan, Italy. PI: Dr. Giulio Cerea, MD.
Funding
Has not received any funding.
Disclosure
D. Signorelli: Financial Interests, Personal, Advisory Board: AstraZeneca, Sanofi, BMS, MSD. M. Brambilla: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Other, Travel Grant: BMS, Italfarmaco. R. Giusti: Financial Interests, Personal, Expert Testimony, Advisory Board for Clinician's expertise on Drug Management: Roche; Financial Interests, Personal, Invited Speaker, Pubblication fee for open access manuscript: Molteni; Financial Interests, Personal, Advisory Board, Advisory Board: Novartis. M. Russano: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Boehringer, BMS, Roche, Merck and Co. A. Russo: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Novartis, Pfizer; Financial Interests, Personal, Writing Engagements: AstraZeneca, Novartis. A.J. Gelibter: Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, Boehringer. D.L. Cortinovis: Financial Interests, Personal, Advisory Board: BMS, Roche, MSD, Novartis, AstraZeneca, Boehringer, Amgen. A. Sartore Bianchi: Financial Interests, Personal, Advisory Board: Amgen, Sanofi, Servier; Financial Interests, Personal, Invited Speaker: Bayer. S. Siena: Financial Interests, Personal, Advisory Board: Amgen, Bayer, BMS, CheckmAb, Daiichi Sankyo, Guardant Health, Roche-Genentech, Novartis, Merck, Seattle Genetics. All other authors have declared no conflicts of interest.