Larotrectinib efficacy in patients with TRK fusion cancer and primary CNS tumors or brain metastases
A new analysis from clinical trials in patients with TRK fusion cancer and brain metastases or primary tumors of the central nervous system ( CNS ) has confirmed the strong activity of Larotrectinib ( Vitrakvi ) in both adults and children.
In TRK fusion cancer patients with intracranial disease, the compound achieved responses and durable disease control, across age or tumor histology.
The analysis has included 14 evaluable patients with primary CNS tumors, including cases of glioma, glioblastoma, glioneural tumors, and astrocytoma.
The overall response rate ( ORR ) was 36% ( n=5; 95% CI: 13-65 ) with two complete responses ( CR ) and three partial responses ( PR ).
In all other patients ( 64%, n=9 ), stable disease was achieved.
For 71% of patients with primary CNS tumors, disease control ( defined as CR plus PR plus stable disease, SD ) was achieved for 24 weeks or more.
In evaluable patients with NTRK gene fusion positive solid tumors with brain metastases ( n=5 ), the ORR was 60% ( n=3 PRs; 95% CI: 15-95 ), and stable disease was achieved in 40% ( n=2 ) of patients.
Twenty four patients with intracranial disease were identified from three clinical studies ( adult phase I trial, NCT02122913, one patient; pediatric phase I trial SCOUT, NCT02637687, 12 patients; and the adult / adolescent phase II basket trial NAVIGATE, NCT02576431, 11 patients ).
Eighteen patients presented with primary CNS tumors ( data cut-off February 19, 2019 ), of which 14 were evaluable, and six patients had brain metastases, of which five were evaluable ( data cut-off July 30, 2018 ).
Safety data are consistent with previous publications, with the majority of adverse events being grade 1 or 2.
Of the five evaluable patients with brain metastases, three had a partial response and two achieved stable disease based on investigator assessment by RECIST ( Response Evaluation Criteria In Solid Tumors ) 1.1.
Four patients remained on treatment at the time of data cut-off, with treatment durations ranging up to 18.4 months.
In the 14 evaluable patients with primary CNS tumors, two patients ( 14% ) achieved a complete response and three patients ( 21% ) had a partial response.
In all other patients ( 64%, n=9 ), stable disease was achieved based on investigator assessment by RECIST 1.1 or RANO ( Response Assessment in Neuro-Oncology ).
The disease control rate ( DCR, defined as CR plus PR plus SD for 24 weeks or more ), was 71%.
Thirteen patients remained on treatment at time of data cut-off, with treatment durations ranging up to 16.6 months.
TRK fusion cancer occurs when an NTRK gene fuses with another unrelated gene, producing an altered TRK protein. The altered protein, or TRK fusion protein, becomes constitutively active or overexpressed, triggering a signaling cascade.
These TRK fusion proteins can act as an oncogenic driver, promoting cell proliferation and survival in tumor cell lines, leading to TRK fusion cancer, regardless of where it originates in the body.
TRK fusion cancer is not limited to certain types of tissues and can occur in any part of the body.
TRK fusion cancer occurs in various adult and pediatric solid tumors with varying frequency, including lung, thyroid, GI cancers ( colon, cholangiocarcinoma, pancreatic and appendiceal ), sarcoma, CNS cancers ( glioma and glioblastoma ), salivary gland cancers ( mammary analogue secretory carcinoma ) and pediatric cancers ( infantile fibrosarcoma and soft tissue sarcoma ). ( Xagena )
Source: Bayer, 2019