Abstract 991P
Background
About 4% of all EGFR mutations account as exon 20 insertions, which convey resistance to the first three generations of EGFR-tyrosine kinase inhibitors (TKIs). Recent research has revealed new drugs to target these mutations specifically. However, little is known about the impact of immune-checkpoint blockade (ICB) in this subgroup, especially in patients with co-occurring TP53 mutations.
Methods
We analyzed co-occurring mutations in patients with EGFR exon 20 insertions and their influence on the efficacy of systemic treatment. The main focus was impact of ICB on overall survival (OS) in these patients with or without TP53 mutations. Co-mutational status was assessed using next-generation-sequencing (NGS) panels. TP53 mutations were further divided into truncating vs. non-truncating mutations.
Results
Real-world-data (RWD) of 159 advanced NSCLC patients with EGFR exon 20 insertion in the timeframe of 2014-2020 were analyzed. TP53 mutation was the most common co-occurring mutation in 69 (43.6%) patients. OS of TP53 wildtype patients was significantly longer with 851 vs. 444 days (p=0.003, Log Rank). No difference of OS referring to the subtype of TP53 mutations was observed (p=0.703). In total, 66 pts were treated with ICB in one of the treatment lines and trended towards longer OS of 824 vs. 479 days, without reaching significance (p=0.402). In patients with co-occurring TP53, patients who received ICB (n=33) had longer OS than those without ICB exposure (507 vs. 369 days, p=0.086). Lack of significance might be explainable by a median follow-up time of 1498 days (4.1 years).
Conclusions
Regardless of subtype, TP53 co-occurring mutation seems to be a strong negative prognostic factor in NSCLC patients with EGFR exon 20 insertions. However, these patients seem to benefit from the ICB, especially at the beginning of their treatment pathway.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Universitätsklinikum Köln for the Network Genomic Medicine (NGM).
Funding
Conducted by Universitätsklinikum Köln, partly funded by Janssen-Cilag GmbH.
Disclosure
M. Scheffler: Financial Interests, Personal, Invited Speaker: Amgen, Boehringer Ingelheim, Takeda, Pfizer, Roche, Sanofi-Aventis, Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Amgen, Boehringer Ingelheim, Roche, Novartis, Takeda, Pfizer; Financial Interests, Personal, Expert Testimony: Amgen, Pfizer, Amgen, Takeda; Financial Interests, Institutional, Invited Speaker: Dracen Pharmaceuticals, Amgen, Dracen, Siemens Healthineers; Non-Financial Interests, Advisory Role, Patient advocacy: zielgenau e. V., YesWeCan(cer); Non-Financial Interests, Principal Investigator, YouTube channel for patients: OncoEducation. F. Kron: Financial Interests, Personal, Ownership Interest: Vitis Healthcare Group. S. Loges: Financial Interests, Personal, Invited Speaker: BerGenBio AS, BMS, Eli Lilly, Boehringer Ingelheim, Roche Pharma, Medac GmbH, Sanofi-Aventis, Novartis, AstraZeneca, Pfizer, Takeda, Amgen, Janssen, Merck; Financial Interests, Personal, Advisory Board: BerGenBio AS, BMS, Eli Lilly, Boehringer Ingelheim, Roche Pharma, Sanofi-Aventis, Novartis, AstraZeneca, Pfizer, Takeda, Amgen; Financial Interests, Institutional, Invited Speaker: BerGenBio AS; Financial Interests, Institutional, Research Grant: BMS, Eli Lilly, Roche Pharma, ADC Therapeutics; Non-Financial Interests, Member: DGHO, ASCO, AIO. J. Wolf: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Blueprint, BMS, Boehringer Ingelheim, Daiichi Sankyo, Ignyta, Janssen, Lilly, Loxo, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda; Financial Interests, Personal, Invited Speaker: Bayer, Chugai; Financial Interests, Institutional, Research Grant: BMS, Janssen, Novartis, Pfizer. All other authors have declared no conflicts of interest.