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Osimertinib plus anlotinib for advanced NSCLC with acquired EGFR T790M mutation: results from a multicenter phase II
Xinyue Wang1, Zhaona Li2, Liuchun Wang1
1Department of Thoracic Oncology, Tianjin Lung Cancer Center, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute & Hospital, Tianjin, 300060, P. R. China.
Background:
Osimertinib is a standard treatment for first- or second-line therapy in patients with non-small cell lung cancer (NSCLC) harboring mutations in the epidermal growth factor receptor (EGFR). However, options are limited for patients with acquired EGFR T790M mutations resistant to first- or second-generation EGFR-tyrosine kinase inhibitors (TKIs). This study assessed the efficacy and safety of combining osimertinib with anlotinib in this patient population and explored circulating tumor DNA (ctDNA) as a biomarker of treatment outcomes.
Methods:
In this prospective, single-arm, phase II trial, 31 patients with advanced NSCLC resistant to prior first- or second-generation EGFR-TKIs therapy received osimertinib (80 mg daily) and anlotinib (12 mg daily on days 1-14 of each 21-day cycle). Efficacy endpoints included progression-free survival (PFS) and overall survival (OS). ctDNA was analyzed using next-generation sequencing (NGS) to monitor mutation status and treatment response.
Results:
The median PFS was 16.2 months (95% confidence interval [CI] 9.8-23.6, 90% CI 14.2-20.9), and the median OS was 31.4 months (95% CI 27.3-not reached). The objective response rate (ORR) was 45.2% (95% CI 30.6-66.6%), with a disease control rate (DCR) of 96.8% (95% CI 86.3-100.0%). ctDNA analysis showed that activating EGFR mutation clearance after two treatment cycles correlated with significantly longer PFS and OS. The regimen was well-tolerated, with no grade 4 or higher adverse events observed.
Conclusions:
Osimertinib combined with anlotinib demonstrates promising long-term efficacy and manageable safety in EGFR T790M-positive NSCLC. Clearance of ctDNA, particularly of EGFR mutations, could serve as a valuable predictive biomarker, supporting the implementation of personalized treatment strategies.
Trial Registration:
ClinicalTrials.gov, NCT04029350.
Insights
Combining osimertinib with anlotinib shows promising efficacy for non-small cell lung cancer (NSCLC) patients with acquired EGFR T790M mutations. Circulating tumor DNA (ctDNA) clearance predicts better outcomes, supporting personalized treatment strategies.
Area of Science:
- Oncology
- Medical Science
Background:
- Osimertinib is a standard first- or second-line treatment for non-small cell lung cancer (NSCLC) with EGFR mutations.
- Limited treatment options exist for patients with acquired EGFR T790M resistance to earlier EGFR-TKIs.
- This study investigates the combination of osimertinib and anlotinib for this patient group.
Purpose of the Study:
- To assess the efficacy and safety of combining osimertinib with anlotinib in advanced NSCLC patients resistant to prior EGFR-TKIs.
- To explore circulating tumor DNA (ctDNA) as a biomarker for treatment outcomes in this population.
Main Methods:
- A prospective, single-arm, phase II trial involving 31 patients with advanced NSCLC.
- Patients received daily osimertinib (80 mg) and anlotinib (12 mg on days 1-14 of a 21-day cycle).
- Efficacy endpoints included progression-free survival (PFS) and overall survival (OS); ctDNA was analyzed via next-generation sequencing (NGS).
Main Results:
- Median PFS was 16.2 months and median OS was 31.4 months.
- Objective response rate (ORR) was 45.2% and disease control rate (DCR) was 96.8%.
- Clearance of ctDNA, specifically EGFR mutations, after two cycles correlated with significantly longer PFS and OS. The regimen was well-tolerated with no grade 4+ adverse events.
Conclusions:
- Osimertinib plus anlotinib demonstrates significant long-term efficacy and manageable safety in EGFR T790M-positive NSCLC.
- ctDNA clearance, particularly EGFR mutations, serves as a predictive biomarker for treatment response.
- This combination therapy and biomarker approach support personalized treatment strategies for NSCLC.
