Larotrectinib (Vitrakvi) led to high and durable responses in patients with NTRK fusions, irrespective of prior therapy or ECOG performance status (PS), according to David S. Hong, MD, who presented a pooled analysis from 3 clinical trials that evaluated the agent in patients with NTRK alterations during the 2020 AACR Virtual Annual Meeting I.
“Patients with NTRK fusions who have had a significant number of prior therapies can benefit from larotrectinib. In some cases, this has to be looked at on the ground level, but even some patients with an ECOG PS of 3 can benefit from NTRK inhibition,” said Hong.
In the first analysis, patients were stratified according to the number of prior lines of therapy they had received (0, 1, 2, or 3 or greater) and baseline ECOG PS (0, 1, 2, or 3). The objective response rate (ORR) was highest in previously untreated patients with an ECOG PS of 0 (91%). However, larotrectinib showed benefit across each group, reaching an ORR of 85% in patients who had received at least 3 lines of prior therapy and 33% in patients with an ECOG PS of 3.1
However, the benefit of larotrectinib did not extend to patients with other NTRK alterations beyond fusions. In the second analysis, investigators evaluated the efficacy of larotrectinib in patients according to NTRK gene status. Among 159 patients with NTRK fusions and 73 patients with non-fusion alterations, including point mutations, amplifications, rearrangements, and deletions, the ORR was 79% in the fusion group versus 1 partial response (PR) in the non-fusion group. Moreover, the median duration of response was 35.2 months and 3.7 months in the fusion and non-fusion groups, respectively.2
In an interview with OncLive, Hong, deputy chair, Department of investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discussed the results of these analyses with larotrectinib in patients with NTRK alterations.
OncLive: What do these long-term data show regarding larotrectinib’s use in patients with NTRK fusions?
Hong: Larotrectinib has been approved for almost 2 years. It’s novel in the sense that it is the first targeted therapy that is approved across tumor types and ages. These data reconfirm the incredible efficacy and incredible safety of this drug in patients with NTRK fusions.
According to the post hoc analysis, how do responses to larotrectinib differ in the NTRK fusion versus non NTRK-fusion populations?
In this analysis, we pooled data from 3 studies [that evaluated larotrectinib in patients with NTRK fusions]: the phase 1 trial in adults (NCT02122913), the phase 1/2 SCOUT trial (NCT02637687) in pediatric patients, and the phase 2 NAVIGATE trial (NCT02576431) in adult and pediatric patients. These 3 trials led to the approval of larotrectinib in patients with NTRK fusions. We wanted to understand the differences in [outcomes] between patients with other NTRK alterations versus those with fusions.
When we started the pediatric and the adult phase 1 trial, there was not a whole lot of data regarding the efficacy of larotrectinib in patients with NTRK fusions or other alterations, such as mutations or amplifications. The phase 1 pediatric and adult trial allowed patients with all tumor types [to enroll]. In the dose-escalation, and, to some extent the expansion portions, we tried to determine whether larotrectinib had some efficacy in patients with other alterations.
Patients with NTRK fusions are relatively rare. Patients with fusions, mutations, amplifications, in addition to patients without those alterations were allowed on the trial. When we looked at the data comparing fusions with these other alterations in this kind of retrospective, pooled analysis, we saw marked differences [in outcomes]. There was a total of 159 patients with NTRK gene fusions compared with 73 patients who had non-fusion tumors. The response rates were dramatically different. The response rate in the NTRK fusion population was 79%, which included a 16% complete response rate compared with patients with other alterations in which only 1 patient had a very short-lived PR.