Abstract 30P
Background
Uncommon EGFR mutations represents a rare subgroup of non-small cell lung cancer. Data on the efficacy of different generations of tyrosine kinase inhibitors (TKIs) in these rare mutations is scattered and limited to mostly retrospective small cohorts, as these patients were usually excluded from clinical trials.
Methods
This was a systematic review on the efficacy of TKIs in patients harboring uncommon EGFR mutations, defined as mutations other than ex20ins or T790M. Response rates (RRs) for different generations of TKIs were determined for individual uncommon mutations, compound mutations, and according to classical-like and P-loop alpha helix compressing mutations classes (PACC). This study was conducted in accordance with the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Results
1,836 patients from 38 studies were included in the final analysis. Most available data (92.6%) were from patients treated with first or second-generation TKIs. G719X, S768I, E709X, L747X and E709-T710delinsD demonstrated RRs ranging from 47.8%-72.3% to second-generation TKIs, generally higher than for 1st or 3rd generation TKIs. L861Q mutation exhibited 75% (95% CI: 56.6-88.5%) RRs to 3rd generation TKIs. Compound mutations with G719X, E709X or S768I consistently showed RRs above 50% to 2nd and 3rd generation TKIs, though fewer data were available for 3rd generations. For classical-like mutations, RRs were 35.4% (95% CI: 27.2-44.2%), 51.9% (95% CI: 44.4-59.3%) and 67.9% (95% CI: 47.6-84.1%) to first, second and third generation TKIs, while for PACC mutations, RRs were 37.2% (95% CI: 32.4-42.1%), 59.6% (95% CI: 54.8-64.3%) and 46.3% (95% CI: 32.6-60.4%) respectively.
Conclusions
This systematic review supports the use of 2nd generation TKI afatinib for G719X, S768I, E709X and L747X mutations, as well as for compound uncommon mutations. For other uncommon mutations such as L861Q, 3rd generation TKI, such as osimertinib, seems a reasonable option, considering its activity and toxicity profile.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
K. Parikh: Financial Interests, Institutional, Other, Consulting fees: Jazz pharmaceuticals; Financial Interests, Institutional, Other, Consuling fees: Guardant Health, AstraZeneca; Financial Interests, Personal, Invited Speaker: MJH Life science; Financial Interests, Institutional, Invited Speaker: Dava Oncology; Financial Interests, Personal, Other, Support for attending meetings/travels: Dava Oncology. G.L. Banna: Financial Interests, Institutional, Speaker’s Bureau: Astellas, Amgen, astrazeneca; Financial Interests, Personal, Other, Support for attending meeting/travel: Janssen, Merck; Financial Interests, Personal, Other, Patent planned/issued: St Microelectronics. X. Le: Financial Interests, Personal, Other, Consulting fees: EMD Serono; Financial Interests, Institutional, Invited Speaker, Consuling fees: Eli Lilly, AstraZeneca, Spectrum pharmaceutics, Novartis, Regeneron, Boehringer Ingelheim, Hengrui, Bayer, Teligene, Taiho, Daiichi Sankyo, Janssen, Blueprint medicines, Sensei Biotherapeutics, Systimmune, ArriVent, Abion, AbbVie; Financial Interests, Personal, Stocks/Shares: BlossomHill; Financial Interests, Personal, Other, Support for attending meeting/travel: EMD Serono, Janssen, Spectrum pharmaceutics; Financial Interests, Personal and Institutional, Research Grant: Eli Lilly, EMD Serono, ArriVent, Dizal, Teligene, Regeneron, Janssen, Thermo Fisher, Takeda, Boehringer Ingelheim. A. Addeo: Financial Interests, Institutional, Advisory Board: BMS, AZD, Roche, Eli Lilly; Financial Interests, Personal, Advisory Board: Pfizer, Takeda, MSD; Financial Interests, Institutional, Invited Speaker: Novartis. All other authors have declared no conflicts of interest.