Abstract 3663
Background
Although liquid biopsy has been reported in detecting actionable mutations, and is becoming standard of care in non-small cell lung cancer (NSCLC) under certain circumstances, the relationship between plasma mutant allele fractions (MAFs) and treatment responsiveness remains unclear.
Methods
This study enrolled 134 patients with advanced NSCLC. Tumor tissue specimens were collected after surgery, and peripheral blood samples were collected at baseline (before surgery) and during treatments. Amplification-refractory mutation system (ARMS) was performed for EGFR mutation screening in all tumor tissues. Circulating single-molecule amplification and resequencing technology (cSMART) was performed in all cfDNA samples using a panel of nine genes including EGFR. EGFR status were compared between tumor tissue and matched cfDNA samples. Moreover, the association between MAFs of EGFR mutations in cfDNA and the responsiveness to tyrosine-kinase inhibitor (TKI) treatment was analyzed.
Results
EGFR mutations were detected in 56 tumor samples (56/134, ∼41.8%) and 67 matched baseline plasma cfDNA samples (67/134, 50.0%), the concordance rate between tumor and cfDNA samples is 82.8%. Specifically, EGFR exon19 non-frameshift deletions were detected in 24 tumor tissue and 23 matched cfDNA samples (concordance rate 97.8%), EGFR p.L858R mutations were detected in 24 tumor tissue and 22 matched cfDNA samples (concordance rate 97.0%). The overall response rate (ORR) and disease control rate (DCR) for EGFR mutation positive patients (TKI sensitive mutations only) were 47.6% and 73.8%, respectively. More importantly, for TKI-treated patients with original plasma EGFR MAFs higher than 0.1% and lower than 0.1%, the ORRs were 58.6% and 23.1% (17/29 versus 3/13 patients, P = 0.047), respectively.
Conclusions
In this study we confirmed that liquid biopsy based screening is reliable for actionable somatic mutation detection. The plasma mutant allele fraction of EGFR driver mutation tend to associate with the responsiveness to TKI targeted treatment. Larger cohorts are needed to clarify the impact of plasma MAFs in predicting treatment responsiveness.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4085 - A Phase 1, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ADCT-601 in Patients with Advanced Solid Tumors
Presenter: Anthony Tolcher
Session: Poster Display session 1
Resources:
Abstract
1054 - Safety, efficacy, and pharmacokinetic (PK) profile of cosibelimab, an anti‐PD‐L1 antibody, in patients (pts) with advanced cancers
Presenter: Philip Clingan
Session: Poster Display session 1
Resources:
Abstract
4264 - A Phase I study of tinostamustine in patients (pts) with advanced solid tumours
Presenter: Alain Mita
Session: Poster Display session 1
Resources:
Abstract
3811 - Lurbinectedin (LUR) in combination with Irinotecan (IRI) in patients (pts) with advanced solid tumors
Presenter: Santiago Ponce Aix
Session: Poster Display session 1
Resources:
Abstract
1311 - A phase I study of varlitinib (VAR; ASLAN001) an oral pan-HER tyrosine kinase inhibitor (TKI) combined with mFOLFIRI chemotherapy in advanced solid tumors
Presenter: Aaron Tan
Session: Poster Display session 1
Resources:
Abstract
3482 - Phase I study of lapatinib and trametinib in patients with KRAS mutant colorectal, non-small cell lung and pancreatic cancer
Presenter: Sanne Huijberts
Session: Poster Display session 1
Resources:
Abstract
4749 - Pharmacokinetic (PK) and updated survival data from the Canadian Cancer Trials Group IND.226 study of durvalumab ± tremelimumab in combination with platinum-doublet chemotherapy
Presenter: Desiree Hao
Session: Poster Display session 1
Resources:
Abstract
4530 - A Phase 2a clinical trial combining ALRN-6924 and palbociclib for the treatment of patients with tumors harboring wild-type p53 and MDM2 amplification or MDM2/CDK4 co-amplification
Presenter: Funda Meric-Bernstam
Session: Poster Display session 1
Resources:
Abstract
4280 - Updated Efficacy and Safety of Entrectinib in Patients with NTRK Fusion-Positive Tumors: Integrated Analysis of STARTRK-2, STARTRK-1 and ALKA-372-001
Presenter: Christian Rolfo
Session: Poster Display session 1
Resources:
Abstract
6144 - An international randomized cross-over bio-equivalence study of oral paclitaxel + HM30181 compared with weekly intravenous (IV) paclitaxel in patients with advanced solid tumors
Presenter: Christopher Jackson
Session: Poster Display session 1
Resources:
Abstract