A pooled analysis of 3 phase 1/2 clinical trials assessing larotrectinib (Vitrakvi) as first-line treatment for adult and pediatric patients with metastatic/unresectable TRK fusion cancer who have not received prior systemic therapy demonstrated promising efficacy and safety data.1
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The analysis also demonstrated extended survival, with a median progression-free survival of 61 months (95% CI, 33–NE) and 5-year overall survival (OS) rate of 76% (95% CI, 65%–86%) for all patients. The median OS was not reached.
Regarding safety, the agent was found to be well tolerated, with most treatment-related adverse events (TRAEs) being grade 1/2. One patient discontinued larotrectinib due to a TRAE (hypoventilation).
“This series of trials was the first to [analyze] the efficacy and safety of larotrectinib in a combined population of adult and [pediatric] patients with TRK fusion cancer who had not previously received systemic therapy in a metastatic or unresectable setting,” said the investigators, Hong et al, in the paper.1
“While no randomized controlled data on larotrectinib exist, these results further reinforce its robust efficacy and [favorable] safety profile, as observed in earlier pooled analyses of the three single arm trials,” they noted.
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Notably, of the tumor types evaluated, the agent was found to be the most efficacious in patients with (IFS), with an ORR of 100%. However, the investigators note that the correlation between young age, diagnosis, and absence of metastatic disease in these patients may confound these results.1
“While the use of larotrectinib in the first-line setting is specified in certain [tumor] guidelines (eg. non–small cell lung cancer), these results suggest that its first-line use could be considered as a valuable option in a wider variety of [tumors],” the investigators added.
What Were the 3 Constituent Trials?
The analysis included 101 patients across 3 trials sponsored by Bayer:
- Phase 1 trial (NCT02122913): A randomized, open-label study measuring the safety and pharmacokinetic profile of larotrectinib in adults with cancer.2 Five patients were included for analysis.
- Phase 1/2 SCOUT trial (NCT02637687): A nonrandomized, open-label study testing the safety and response of larotrectinib in pediatric patients with cancer.3 Forty-two patients were included for analysis.
- Phase 2 NAVIGATE trial (NCT02576431): A nonrandomized, open-label, phase 2 study assessing the efficacy of larotrectinib in adult and pediatric patients with cancer.4 Fifty-four patients were included for analysis.
What Was Found Regarding Treatment Discontinuation and Disease Progression?
In addition to the efficacy and safety findings, the study also reported results from the “wait-and-see” analysis from the SCOUT trial, where 25 of 42 pediatric patients elected to stop larotrectinib in the absence of on-treatment disease progression and were actively followed for disease progression.
By the end of the first “wait-and-see” period, over half of the patients had experienced disease progression; however, a response was achieved in over half of these patients upon continuation of larotrectinib, supporting potential elective treatment discontinuation for select populations.1 However, more research is needed to determine an optimal treatment duration and to generate evidence on treatment discontinuation in adults.