Abstract 495P
Background
Osimertinib has been established as standard treatment for patients with advanced EGFR-mutated NSCLC. We assessed the clinical relevance of EGFR mutation tracking in plasma circulating tumor DNA (ctDNA) after initiation of osimertinib therapy in patients who were pre-treated with EGFR-tyrosine kinase inhibitors (TKIs).
Methods
Plasma samples of 106 patients with advanced EGFR-mutated NSCLC who received second-line osimertinib after detection of T790M mutation in plasma ctDNA and/or tissue re-biopsy were collected under osimertinib therapy. Plasma ctDNA was tested for EGFR deletions in exon 19, L858R, L861Q, S768I, T790M and C797S mutations using droplet digital PCR (ddPCR). Primary endpoint was progression-free survival (PFS). Univariate and multivariable Cox proportional hazard models were used to evaluate the risk of progression.
Results
In 57 out of 106 patients plasma samples were available within the first 8 weeks after osimertinib therapy initiation. Within this time frame, the activating mutation remained detectable in plasma of 19/57 patients (33%) and the T790M mutation in 8/57 patients (14%). The C797S mutation was not detectable within 8 weeks after osimertinib start. Patients with persistence of the activating EGFR mutation in plasma ctDNA within 8 weeks after osimertinib initiation had a shorter PFS compared to patients who had lost the activating EGFR mutation (median PFS 3.4 versus 26.9 months; hazard ratio [HR] 6.17, 95% confidence interval [CI] 3.03-12.56, p < 0.0001). Similarly, detection of T790M in plasma ctDNA was also associated with shorter PFS (median PFS 7.0 versus 19.0 months; HR 2.32, 95% CI 1.00-5.37, p = 0.05). Multivariable analysis using a stepwise backward elimination model demonstrated that persistence of activating EGFR mutations and T790M in plasma ctDNA remained significant predictors of shorter PFS after adjusting for clinical parameters and T790M.
Conclusions
Our results show that tracking of activating EGFR mutations during osimertinib therapy is clinically relevant. Detection of activating EGFR mutations in plasma ctDNA 8 weeks after osimertinib initiation predicts shorter PFS of second-line treatment with osimertinib.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
AstraZeneca.
Disclosure
A. Buder: Honoraria (self): AstraZeneca. M.J. Hochmair: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim. M. Filipits: Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim. All other authors have declared no conflicts of interest.
Resources from the same session
258P - Assessment of sexual health in patients treated for ovarian cancer
Presenter: Renu Madan
Session: Poster display session
Resources:
Abstract
259P - The BOT patients fail to benefit from surgical staging procedures in prognosis and fertility outcomes: A retrospective analysis
Presenter: Li Na
Session: Poster display session
Resources:
Abstract
260P - Malignant ovarian germ cell tumours (MOGCT): Treatment results of 149 pts
Presenter: Dzhennet Chekini
Session: Poster display session
Resources:
Abstract
261P - Ovarian germ cell tumours - challenges and outcomes from a tertiary care centre in South India
Presenter: Vishnu Sreedath
Session: Poster display session
Resources:
Abstract
262P - Gestational trophoblastic tumours: Experience of the medical oncology department Hassan II University Hospital-Morocco about 29 cases
Presenter: Karima Oualla
Session: Poster display session
Resources:
Abstract
263TiP - ATHENA (GOG-3020/ENGOT-ov45): A randomised, double-blind, placebo-controlled phase III study of the poly (ADP-ribose) polymerase (PARP) inhibitor rucaparib + the PD-1 inhibitor nivolumab following frontline platinum-based chemotherapy in ovarian cancer
Presenter: Keiichi Fujiwara
Session: Poster display session
Resources:
Abstract
264TiP - ENGOT-ov43/KEYLYNK-001: A phase III trial of pembrolizumab plus chemotherapy with olaparib maintenance for first-line treatment of BRCA¬-nonmutated advanced epithelial ovarian cancer
Presenter: Keiichi Fujiwara
Session: Poster display session
Resources:
Abstract
265TiP - KEYNOTE-826: A phase III randomized study of chemotherapy with or without pembrolizumab for first-line treatment of persistent, recurrent, or metastatic cervical cancer
Presenter: Keiichi Fujiwara
Session: Poster display session
Resources:
Abstract
271P - Comparison between CHOP like regimens and DAEPOCH with or without Rituximab in adult high grade B cell lymphoma NOS; A retrospective study from a tertiary cancer hospital in South India
Presenter: LALATENDU MOHARANA
Session: Poster display session
Resources:
Abstract
272P - Melatonin increases the chemosensitivity of diffuse large Bell lymphoma cells to Epirubicin by inhibiting P-glycoprotein expression via the NF-κB pathway
Presenter: Xiuhua Sun
Session: Poster display session
Resources:
Abstract