The highly selective TRK inhibitor Larotrectinib ( Vitrakvi ) is approved for the treatment of adult and pediatric cancers that harbor NTRK gene fusions; it achieves a 79% overall response rate ( ORR ) in this population ( Hong et al., Lancet Oncol 2020 ).
The activity of Larotrectinib in adults alone was further characterized in this update with a larger series of patients and more mature durability data.
Adults ( aged 18 years or older ) with TRK fusion cancer treated in three Larotrectinib clinical trials ( NCT02122913, NCT02576431, and NCT02637687 ) were analyzed.
Larotrectinib was administered 100 mg BID until disease progression, withdrawal, or unacceptable toxicity.
ORR was investigator-assessed ( RECIST v1.1 ).
Compared to previously presented data on 74 patients, this expanded data set has included an additional 42 patients ( data cutoff: July 15, 2019 ).
116 adults ( median age: 56 years, range 19–84 years; 53% female ) with TRK fusion cancer were treated.
Tumor types included thyroid cancer ( 22% ), salivary gland cancer ( 19% ), soft tissue sarcoma ( 16% ), lung cancer ( 12% ), colon cancer ( 7% ), melanoma ( 5% ), breast cancer ( 5% ), GIST ( 3% ), and 9 other types ( 2% or less each ).
NTRK fusions involved NTRK1 ( 43% ), NTRK2 ( 3% ), and NTRK3 ( 54% ).
78% of patients had received prior systemic therapy ( with 68% of those receiving 2 or more prior therapies ).
The ORR was 71% ( 95% CI 62–79 ): 10% complete response [ CR ], 60% partial response [ PR ] ( 2% pending confirmation ), 16% stable disease, 9% progressive disease, 3% not determined.
In patients with brain metastases, the ORR was 71% ( 95% CI 42–92; 10 of 14 patients, all partial responses ).
Median duration of response for the overall data set ( n = 116 ) was 35.2 months ( 95% CI 21.6–not estimable [ NE ] ).
Median progression-free survival was 25.8 months ( 95% CI 15.2–NE ). Median overall survival was not reached ( range 0.5+ to 51.6+ months ) at a median follow-up of 15.8 months.
Duration of treatment ranged from 0.10 to 51.6+ months.
12% of patients had dose reductions. One patient ( 1% ) discontinued due to a Larotrectinib-related adverse event.
Adverse effects were mostly grade 1–2; no new unexpected adverse effects were reported.
In conclusion, in an expanded data set of adults with TRK fusion cancer, Larotrectinib demonstrated robust and durable tumor-agnostic efficacy and favorable safety, supporting NTRK gene fusion testing in patients with solid tumors of any type. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020