Abstract 1214P
Background
Clinical benefit to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI’s) is lacking for non-small cell lung cancer (NSCLC) patients with an EGFR exon 20 mutation (EGFRex20+), with known response rate (RR) from 0-28%, and median progression free survival (PFS) of ∼3 months to 1st and 2nd generation EGFR TKI’s (Remon, Cancer Treatment Reviews 2020). A high dose of the 3rd generation TKI osimertinib shows promising antitumor activity to EGFRex20+ in vitro. The safety and efficacy results from a multicenter single arm phase II study investigating osimertinib in EGFRex20+ NSCLC patients are reported here.
Methods
EGFRex20+ (mutation, deletion and/or insertion), T790M negative, advanced NSCLC patients with WHO PS 0-2 were treated with osimertinib 160mg QD till progression or unacceptable toxicity. We allowed patients to be pre-treated (chemo- or immunotherapy) or/and have asymptomatic brain metastases. Primary endpoint: investigator assessed RECIST 1.1 objective response rate (ORR). Secondary outcomes: duration of response (DoR), PFS, overall survival (OS) and treatment related adverse events (TRAEs).
Results
From June 2018 to April 2021, 24 patients were enrolled at 4 centers in the Netherlands. The exon 20 mutations were clustered between A763 and D777. The most common mutation was N771_H773duplication (n=3). 6 patients had a response (ORR 27%, 1 complete, 5 partial), 12 had stable disease and 4 progressive disease (PD) as best response. Median DoR was 8.2 months. The median PFS was 5.5 (95% CI 2.0-9.0) months and the median OS was 15.8 (95% CI 13.8-17.8) months. Primary reasons for discontinuation were PD in 12/24 patients (50%) or due to grade 3 TRAE (2/24 [8%], including pneumonitis [n=1] and left ventricular systolic dysfunction [n=1]). A dose reduction to 80mg was required in 5 patients (21%), of which 2 were due to grade 3 TRAE’s (diarrhea and hepatotoxicity) and 3 were due to grade 2 TRAE’s (QTc prolongation, nausea and increased CPK in combination with myalgia).
Conclusions
The POSITION20 study shows antitumor activity in EGFRex20+ NSCLC patients treated with 160mg osimertinib, with an ORR of 27%. The TRAEs are consistent with other reports.
Clinical trial identification
NTR6875.
Editorial acknowledgement
Legal entity responsible for the study
A.J. van der Wekken (P.I.) (University Medical Center Groningen).
Funding
AstraZeneca.
Disclosure
L.E.L. Hendriks: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Roche; Non-Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim; Non-Financial Interests, Institutional, Advisory Board: BMS; Non-Financial Interests, Institutional, Advisory Board: Lilly. T.J.N. Hiltermann: Non-Financial Interests, Institutional, Advisory Board: BMS; Non-Financial Interests, Institutional, Advisory Board: MSD; Non-Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim; Non-Financial Interests, Institutional, Advisory Board: Pfizer. A.C. Dingemans: Non-Financial Interests, Institutional, Advisory Board: Roche; Non-Financial Interests, Institutional, Advisory Board: Eli Lilly; Non-Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim; Non-Financial Interests, Institutional, Advisory Board: AstraZeneca; Non-Financial Interests, Institutional, Advisory Board: Pfizer; Non-Financial Interests, Institutional, Advisory Board: BMS; Non-Financial Interests, Institutional, Advisory Board: Amgen; Non-Financial Interests, Institutional, Advisory Board: Novartis; Non-Financial Interests, Institutional, Advisory Board: MSD; Non-Financial Interests, Institutional, Advisory Board: Takeda; Non-Financial Interests, Institutional, Advisory Board: PharmaMar. C. van der Leest: Non-Financial Interests, Institutional, Advisory Board: BMS; Non-Financial Interests, Institutional, Advisory Board: MSD; Non-Financial Interests, Institutional, Advisory Board: AstraZeneca; Non-Financial Interests, Institutional, Advisory Board: Roche; Non-Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim. A.J. de Langen: Non-Financial Interests, Institutional, Advisory Board: AstraZeneca; Non-Financial Interests, Institutional, Advisory Board: BMS; Non-Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim; Non-Financial Interests, Institutional, Advisory Board: Pfizer; Non-Financial Interests, Institutional, Advisory Board: Lilly; Non-Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: MSD. M. van den Heuvel: Financial Interests, Institutional, Sponsor/Funding: AstraZeneca; Financial Interests, Institutional, Sponsor/Funding: BMS; Financial Interests, Institutional, Sponsor/Funding: Merck Serono; Financial Interests, Institutional, Sponsor/Funding: MSD; Financial Interests, Institutional, Sponsor/Funding: Novartis; Financial Interests, Institutional, Sponsor/Funding: Pfizer; Financial Interests, Institutional, Sponsor/Funding: Roche (diagnostics); Financial Interests, Institutional, Sponsor/Funding: AbbVie. A.J. van der Wekken: Non-Financial Interests, Institutional, Advisory Board: Lilly; Non-Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim; Non-Financial Interests, Institutional, Advisory Board: Pfizer; Non-Financial Interests, Institutional, Advisory Board: AstraZeneca; Non-Financial Interests, Institutional, Advisory Board: MSD; Non-Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Research Grant, All payments to UMCG: AstraZeneca; Financial Interests, Institutional, Research Grant, All payments to UMCG: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant, All payments to UMCG: Pfizer; Financial Interests, Institutional, Research Grant, All payments to UMCG: Roche; Financial Interests, Institutional, Research Grant, All payments to UMCG: Takeda. All other authors have declared no conflicts of interest.