Abstract 192P
Background
Clearance of plasma epidermal growth factor receptor mutations (pEGFR) post-tyrosine kinase inhibitors (TKI) correlates with improved survival. While droplet digital polymerase chain reaction (ddPCR) and plasma next generation sequencing (NGS) are widely used for diagnosis, head-to-head comparisons are scarce. We sought to compare the performance of ddPCR and Oncomine Pan-Cancer Cell-Free Assay®, a 52-gene NGS panel, in detecting clearance of pEGFR as a predictor of response to EGFR TKI.
Methods
Treatment-naïve advanced EGFR-mutated lung cancer patients treated with first-line TKI at National Cancer Centre Singapore were included. pEGFR were measured at baseline and first response assessment using both ddPCR and NGS. Clearance of pEGFR was defined as undetectable levels after a positive baseline result. Results were correlated with time to treatment failure (TTTF). In exploratory analysis, corresponding change in CEA levels was evaluated.
Results
27 patients were recruited over 1/1/2020–31/12/2021. Median age at diagnosis was 63, 19 (70%) were males and 17 (63%) were never-smokers. Ex19del comprised 74% (20/27) and L858R 26% (7/27). Osimertinib was used in 59% (16/27), Dacomitinib in 4% (1/27) and Gefitinib/Erlotinib in 37% (10/27). Sensitivity of ddPCR and NGS in detecting pEGFR mutation at baseline was 70% (19/27) and 78% (21/27) respectively (p = 0.16). All patients with detectable pEGFR by ddPCR were detected by NGS. At median 8 weeks (range 3–24) post-TKI initiation, clearance of pEGFR was achieved in 68% (13/19) and 71% (15/21) using ddPCR and NGS respectively. The concordance between ddPCR and NGS was 79% (kappa = 0.513, p = 0.013). Clearance of pEGFR was associated with longer median TTTF (not reached versus 6 months, log-rank p = 0.01). Paired CEA results were available for 14 (52%) patients. Clearance of pEGFR was associated with median decrease in CEA levels by 70% from baseline.
Conclusions
Plasma NGS trended towards higher sensitivity than ddPCR in detecting pEGFR at baseline, although both had similar concordance in detecting clearance of pEGFR. Clearance of pEGFR was predictive of improved TTTF. Our results support using NGS at diagnosis and ddPCR for monitoring response, whereas decrease in CEA levels could be explored as a surrogate for pEGFR clearance.
Legal entity responsible for the study
Lung Cancer Consortium Singapore.
Funding
National Medical Research Council of Singapore.
Disclosure
P.L.S. Saw: Financial Interests, Institutional, Invited Speaker: AstraZeneca, MSD; Financial Interests, Institutional, Advisory Board: Pfizer, Bayer, AstraZeneca; Financial Interests, Institutional, Research Grant: Guardant Health, AstraZeneca; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, Novartis, BeiGene, Dracen. A. Tan: Financial Interests, Personal, Advisory Board: Amgen, Bayer, Pfizer. G. Lai: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Amgen, Pfizer, BMS, Roche; Other, Personal, Other, sponsorship for meeting: DKSH. D.W. Lim: Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim, MSD, Pfizer, Novartis; Financial Interests, Institutional, Invited Speaker: Roche, Novartis; Financial Interests, Institutional, Invited Speaker, Grant funding for investigator-sponsored study: Bristol-Myers Squibb. R. Kanesvaran: Financial Interests, Institutional, Invited Speaker: Astellas, Johnson and Johnson, Ipsen, Amgen, BMS, MSD, Novartis, AstraZaneca, Sanofi; Financial Interests, Institutional, Advisory Board: Johnson and Johnson, Pfizer, Ipsen, Amgen, BMS, MSD, Bayer, AstraZaneca, Ferring; Financial Interests, Institutional, Research Grant: Sanofi, Eisai, Johnson and Johnson; Non-Financial Interests, Personal, Leadership Role, Past President: Singapore Society of Oncology; Non-Financial Interests, Personal, Leadership Role, President: SIOG; Non-Financial Interests, Personal, Leadership Role, Vice Chairman: Singapore Cancer Society; Non-Financial Interests, Personal, Leadership Role, Medical Advisory Board Member: International Kidney Cancer Coalition. W.L. Tan: Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Other, Focus Group meeting for expert advice: Merck; Financial Interests, Institutional, Other, Reimbursement for conference meetings: AstraZeneca, Ipsen, Boehringer Ingelheim, Bristol-Myers Squibb, DKSH; Financial Interests, Institutional, Funding, Educational Grant: AstraZeneca; Non-Financial Interests, Personal, Principal Investigator, Clinical trial: Novartis, Amgen. T. Rajasekaran: Financial Interests, Personal, Invited Speaker: Ipsen, MSD; Financial Interests, Personal, Advisory Board: BMS. D.S.W. Tan: Financial Interests, Personal, Advisory Board: Amgen, Novartis, Boehringer Ingelheim, C4 Therapeutics, AstraZeneca, GSK, Takeda, Eisai, Guardant, Merck, Pfizer, Roche; Financial Interests, Institutional, Research Grant: AstraZeneca, Amgen, Pfizer, ACM Biolabs; Financial Interests, Personal, Invited Speaker: Novartis. All other authors have declared no conflicts of interest.