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Efficacy and safety of pyrotinib in advanced lung adenocarcinoma with HER2 mutations: a multicenter, single-arm,
Zhengbo Song1, Yuping Li2, Shiqing Chen3
1Department of Clinical Trial, Zhejiang Cancer Hospital, Hangzhou, 310022, China.
Background:
There is currently a lack of effective treatments for non-small cell lung cancer (NSCLC) patients harboring HER2 mutations. We examined the efficacy and safety of, and potential resistance mechanism to, pyrotinib, a pan-HER inhibitor, in advanced NSCLC carrying HER2 mutations.
Methods:
In this multicenter, single-arm, phase II trial, stage IIIB-IV NSCLC patients harboring HER2 mutations, as determined using next-generation sequencing, were enrolled and treated with pyrotinib at a dose of 400 mg/day. The primary endpoint was 6-month progression-free survival (PFS) rate, and secondary endpoints were objective response rate (ORR), PFS, overall survival (OS), disease control rate (DCR), and safety. The impact of different HER2 mutation types on sensitivity to pyrotinib and the potential of utilizing mutational profile derived from circulating tumor DNA (ctDNA) to predict disease progression were also explored.
Results:
Seventy-eight patients were enrolled for efficacy and safety analysis. The 6-month PFS rate was 49.5% (95% confidence interval [CI], 39.2-60.8). Pyrotinib produced an ORR of 19.2% (95% CI, 11.2-30.0), with median PFS of 5.6 months (95% CI, 2.8-8.4), and median OS of 10.5 months (95% CI, 8.7-12.3). The median duration of response was 9.9 months (95% CI, 6.2-13.6). All treatment-related adverse events (TRAEs) were grade 1-3 (all, 91.0%; grade 3, 20.5%), and the most common TRAE was diarrhea (all, 85.9%; grade 3, 16.7%). Patients with exon 20 and non-exon 20 HER2 mutations had ORRs of 17.7% and 25.0%, respectively. Brain metastases at baseline and prior exposure to afatinib were not associated with ORR, PFS, or OS. Loss of HER2 mutations and appearance of amplification in HER2 and EGFR were detected upon disease progression.
Conclusions:
Pyrotinib exhibited promising efficacy and acceptable safety in NSCLC patients carrying exon 20 and non-exon 20 HER2 mutations and is worth further investigation.
Trial Registration:
Chinese Clinical Trial Registry Identifier: ChiCTR1800020262.
Insights
Pyrotinib shows promising efficacy in advanced non-small cell lung cancer (NSCLC) with HER2 mutations. This pan-HER inhibitor demonstrated acceptable safety and potential in treating NSCLC patients with HER2 exon 20 and non-exon 20 mutations.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) patients with HER2 mutations lack effective treatments.
- Pyrotinib, a pan-HER inhibitor, was investigated for its efficacy and safety in this population.
- Potential resistance mechanisms were also explored.
Purpose of the Study:
- To evaluate the efficacy and safety of pyrotinib in advanced NSCLC patients with HER2 mutations.
- To explore potential resistance mechanisms to pyrotinib.
- To assess the impact of different HER2 mutation types and circulating tumor DNA (ctDNA) profiles on treatment outcomes.
Main Methods:
- A multicenter, single-arm, phase II trial enrolled stage IIIB-IV NSCLC patients with HER2 mutations.
- Patients received pyrotinib 400 mg/day.
- Primary endpoint was 6-month progression-free survival (PFS) rate; secondary endpoints included objective response rate (ORR), PFS, overall survival (OS), disease control rate (DCR), and safety.
Main Results:
- The 6-month PFS rate was 49.5%.
- Pyrotinib achieved an ORR of 19.2%, median PFS of 5.6 months, and median OS of 10.5 months.
- Common treatment-related adverse events (TRAEs) included diarrhea (85.9%); 20.5% of TRAEs were grade 3. Resistance mechanisms like HER2 amplification were observed upon progression.
Conclusions:
- Pyrotinib demonstrated promising efficacy and acceptable safety in NSCLC patients with both exon 20 and non-exon 20 HER2 mutations.
- Further investigation of pyrotinib in this patient group is warranted.
- Mechanisms of resistance involving HER2 and EGFR alterations were identified.
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