Second-line oritinib demonstrated potential clinical benefit in advanced EGFR-mutated NSCLC

Results from a single-arm, phase 2 trial demonstrated a potential clinical benefit of the third-generation EGFR tyrosine kinase inhibitor oritinib in patients with EGFR T790M-mutated non-small cell lung cancer (NSCLC) who had prior treatment with EGFR tyrosine kinase inhibitors.

First-line treatment with an EGFR tyrosine kinase inhibitor is standard of care in patients with locally advanced/metastatic EGFR-mutated NSCLC. However, in most patients treated with first-generation EGFR tyrosine kinase inhibitors, progression of disease eventually occurs due to the development of an EGFR T790M mutation. Second-line treatment with a selective third-generation EGFR tyrosine kinase inhibitor, like osimertinib, has been shown to improve survival over chemotherapy in EGFR T790M-mutated NSCLC patients [1]. Oritinib is a newly developed third-generation EGFR tyrosine kinase inhibitor that was recently tested in a phase 2 trial (NCT03823807) as second-line treatment for patients with locally advanced/metastatic NSCLC who progressed on ≥1 prior first- or second-generation EGFR tyrosine kinase inhibitor and have EGFR T790M-mutated disease. Prof. Caicun Zhou (Shanghai Pulmonary Hospital, China) presented the results of this single-arm study [2].

The trial enrolled 227 patients with locally advanced or metastatic NSCLC and confirmed EGFR T790M mutation. Participants were treated with oritinib 200 mg once daily until disease progression or unacceptable toxicity; 74% of participants were non-smokers, 35% had brain metastases, and 25% had prior chemotherapy. The primary endpoint of the study was objective response rate (ORR); secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and safety.

At data cut-off, ORR was 60.4% (all partial responders), and DCR was 92.5%. Median PFS was 12.6 months and median duration of response was 12.5 months. Overall survival data was immature.

Drug-related adverse events were observed in 84% of participants; these were grade ≥3 in 14% and lead to discontinuation in 1.8% of participants. Most common treatment-related adverse events (grade ≥3) were increased blood creatine phosphokinase, diarrhoea, and decreased lymphocyte count.

Based on these results, Prof. Zhou concluded that treatment with oritinib demonstrated potential clinical benefit in advanced NSCLC patients with EGFR T790M-mutated NSCLC. In addition, oritinib showed a favourable safety profile. A randomised-controlled, double-blind, phase 3 trial is ongoing to compare oritinib with gefitinib as first-line treatment for this population.

1. Nagasaka M, et al. J Thorac Oncol. 2021;16:740–763.
2. Zhou C, et al. Oritinib (SH-1028) a third-generation EGFR tyrosine kinase inhibitor in locally advanced or metastatic NSCLC patients with positive EGFR T790M: Results of a single-arm phase II trial. Abstract 7MO. ELCC 2022 Virtual Meeting, 30 March–02 April.

 

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Posted on 25 May, 2022