Efficacy and safety of Entrectinib in patients with NTRK-fusion positive solid tumors: updated integrated analysis


NTRK gene fusions lead to transcription of chimeric TRK proteins with overexpressed kinase function.
Entrectinib ( Rozlytrek ) is a potent inhibitor of TRKA/B/C. In phase 1/2 studies ( ALKA, STARTRK-1, STARTRK-2; EudraCT 2012-000148-88; NCT02097810; NCT02568267 ), Entrectinib was effective in patients with NTRK-fusion positive solid tumors.

Researchers have presented updated data in a larger population with longer follow-up.

In this integrated analysis of adult patients from 3 phase 1/2 trials ( data cut-off 31 Oct 2018 ), tumors were assessed by blinded independent central review ( BICR ) with RECIST v1.1 ( end of cycle 1; then every 8 weeks ).

Primary endpoints were overall response rate ( ORR ) and duration of response ( DOR ). Secondary endpoints were progression-free survival ( PFS ), overall survival ( OS ), efficacy in patients with/without baseline CNS disease, and safety.

There were 74 evaluable patients with advanced / metastatic NTRK-fp solid tumors.

Median duration of survival follow-up in all patients was 14.2 months ( range 0.1–29.7 ).

BICR ORR was 63.5% ( 95% CI 51.5–74.4 ), with 5 complete responses ( 6.8% ).

Median BICR DOR was 12.9 months ( 95% CI 9.3–NE ); median BICR PFS was 11.2 months ( 95% CI 8.0–15.7 ); median OS was 23.9 months ( 16.0–NE ).

In patients with no baseline CNS disease ( investigator-assessed; n=55 ), BICR ORR was 65.5% ( 95% CI 51.4–77.8 ) and median BICR DOR in responders was 12.9 months ( 95% CI 9.3–NE ).

In patients with baseline CNS disease ( investigator-assessed; n=19 ), BICR ORR was 57.9% ( 95% CI 33.5–79.8 ) and median BICR DOR in responders was 6.0 months ( 95% CI 4.2–NE ).

Safety was in line with that previously reported; the most common grade 3 or more treatment-related adverse effects were weight gain ( 8, 7.1% ), anemia ( 8, 7.1% ), and fatigue ( 7, 6.2% ).

In conclusion, in this updated analysis, including more patients and longer follow-up, Entrectinib continued to demonstrate clinically meaningful responses in patients with NTRK-fusion positive solid tumors, with and without baseline CNS disease. ( Xagena )

Fonte: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020

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