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Barrett H. Childs



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    MA09 - EGFR & MET (ID 128)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
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      MA09.07 - Activity of Larotrectinib in TRK Fusion Lung Cancer (Now Available) (ID 1600)

      15:15 - 16:45  |  Author(s): Barrett H. Childs

      • Abstract
      • Presentation
      • Slides

      Background

      Tropomyosin receptor kinase (TRK) fusions involving NTRK1, NTRK2, and NTRK3 occur in a range of tumor types. Larotrectinib, the first FDA-approved highly selective TRK inhibitor, has demonstrated an overall response rate (ORR) of 75% by independent central review across a broad spectrum of tumors that harbor NTRK gene fusions (Drilon et al., NEJM 2018;378:731–9). Here, we report updated data on the patients with lung cancer who have been treated with larotrectinib.

      Method

      Patients with non-small cell lung cancer (NSCLC) in two clinical trials (NCT02122913 and NCT02576431) with TRK fusion cancer were included in this analysis. Larotrectinib (100 mg BID) was administered on a continuous 28-day schedule until withdrawal, unacceptable toxicity, or disease progression. Response was assessed by investigator (INV) and independent review committee (IRC) per RECIST v1.1.

      Result

      As of July 30, 2018, 11 patients with metastatic lung adenocarcinoma were enrolled. Median age was 52 years (range 25–76 years). Eight patients had fusions involving NTRK1 and diverse fusion partners: EPS15 (n=2), TPM3 (n=2), IRF2BP2 (n=2), TPR (n=1), and SQSTM1 (n=1). Three patients had fusions involving NTRK3 (fusion partner: SQSTM1 [n=2] and ETV6 [n=1]). Ten patients had prior systemic therapy (five patients had three or more prior therapies) with best responses on last prior therapy being one partial response, four with stable disease, three progressive disease, and three unknown or unevaluable. Seven patients were evaluable for response to larotrectinib. INV and IRC assessment were in agreement, with one complete response, four partial responses (including one patient with central nervous system [CNS] metastases), and two with stable disease (ORR 71%). Results from four patients not evaluable at the July 30, 2018 data cut-off due to insufficient follow-up are expected in April 2019 and will be presented at the meeting. The median time to response was 1.8 months. One patient with brain metastases had an intracranial near complete response (–95% reduction) to larotrectinib, as well as an extracranial response. The duration of response by IRC ranged from 7.4+ months to 25.8+ months; the median duration of response was not reached. One patient continued receiving treatment post-progression. Two patients discontinued treatment due to disease progression and one withdrew without cause. Larotrectinib was well tolerated, with treatment-related adverse events being predominantly grade 1–2.

      Conclusion

      Larotrectinib is highly active in advanced lung cancer patients harboring NTRK gene fusions, including those with CNS metastases, with a favorable safety profile. These results support the use of larotrectinib in NTRK fusion NSCLC.

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