1355P - Evaluation of the role of variant allele frequency in EGFR mutated non-small cell lung cancer treated with first line osimertinib

Background

The efficacy of Osimertinib (Osi) in advanced EGFR mutated non-small cell lung cancer (aNSCLC) is associated to type of EGFR mutations (EGFRm) and line of treatment, while the impact of cell clonality is still controversial. We aimed to evaluate the effect of variant allele frequency (VAF), as a surrogate of clonality, in the first line treatment with Osimertinib in EGFR mutated aNSCLC.

Methods

We retrospectively collected data of 60 aNSCLC harbouring a common EGFRm (Ex19dels or Ex21 L858R) treated with at least one cycle of first-line Osi from January 2019 to September 2022 at Fondazione IRCCS Istituto Nazionale Tumori of Milan. Next Generation Sequencing analyses were performed at baseline. According to median VAF (mVAF), patients were divided into two subgroups (VAFhigh > mVAF and VAFlow < mVAF). Differences in median progression free survival (mPFS), objective response rate (ORR) and disease control rate (DCR) between subgroups were analysed. Fisher’s exact test was used to compare proportions. Survival was estimated through Kaplan-Meier method and compared by Cox-proportional Hazard model.

Results

In our cohort, mVAF was 0,39. Baseline characteristics were equally distributed between subgroups. With a median follow up of 14,2 months (mo), mPFS in the overall population was 17 mo (0.95 CI 12,2-30,1). No statistically differences in mPFS were found according to mVAF (HR 1,34, 15 mo 0.95CI [11,8-NA] vs 20,9 mo 0.95CI [11,9-NA], p=0.45, in VAFlow and VAFhigh, respectively). Similarly, mVAF did not impact on DCR and ORR (92,3% vs 96,6%, p=0,922 and 65,5% vs 65,4%, p=1 in VAFhigh vs VAFlow, respectively). Finally, no differences were observed between the two subgroups in terms of clinical characteristics associated with worse prognosis (presence of brain metastasis, number of metastatic sites and TP53 comutation).

Conclusions

Our study suggests that EGFR mVAF has a low impact in predicting the benefit of first-line Osi. Further investigations in a larger cohort and with a longer follow up, including a more comprehensive analysis of the genomic landscape, may help in clarifying the role of VAF in predicting the clinical outcomes to Osi.

Clinical trial identification

NCT05550961.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Brambilla: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Other, Travel fee: Lilly. A. Prelaj: Financial Interests, Personal, Other, Training of personnel: AstraZeneca, Italfarma; Financial Interests, Personal, Invited Speaker, The Hive Project: Discussant: Roche; Financial Interests, Personal, Advisory Board, Advisory board in Lung Cancer project: BMS; Financial Interests, Personal, Other, Travel Grant: Janssen. G. Lo Russo: Financial Interests, Personal, Advisory Board: MSD, Novartis, AstraZeneca, BMS, Pfizer, Roche, Sanofi; Financial Interests, Personal, Invited Speaker: Italfarmaco; Financial Interests, Institutional, Local PI: BMS, MSD, GSK, Celgene, Novartis, Roche, AstraZeneca, Amgen; Financial Interests, Local PI: Sanofi. G. Pruneri: Financial Interests, Personal, Invited Speaker: Roche, Lilly, Exact Sciences, Novartis; Financial Interests, Personal, Advisory Board: Exact Sciences, ADS Biotec; Financial Interests, Institutional, Research Grant: Roche. F.G.M. De Braud: Financial Interests, Personal, Invited Speaker: Amgen, BMS, Dephaforum, ESO, Healthcare Research & Pharmacoepidemiology, Incyte, MSD, Merck Group, Nadirex, Pfizer, Roche, Sanofi, Seagen, Servier, Ambrosetti; Financial Interests, Personal, Other, Consultant: Mattioli 1885 ; Financial Interests, Personal, Other, Think Thank: MCCann Health; Financial Interests, Personal, Other, Consultant Advisory Board: AstraZeneca, MSD, BMS, EMD Serono, Incyte, Menarini, NMS Nerviano Medical Science, Novartis, Pierre Fabre, Roche, Sanofi; Financial Interests, Personal, Coordinating PI: BMS, Basilea Pharmaceutica International AG, Daiichi Sankyo Dev. Limited, Exelixis Inc, F. Hoffmann-LaRoche Ltd, IQVIA, Ignyta Operating INC, Janssen-Cilag International NV, Kymab, Loxo Oncology Incorporated, MSD, MedImmune LCC, Merck KGAA, Merck Sharp & Dohme Spa, Novartis, Pfizer, Tesaro; Financial Interests, Personal, Other, Consultant Adv Board: Taiho. All other authors have declared no conflicts of interest.