Vitrakvi▼ (larotrectinib) has demonstrated efficacy in different solid tumours with NTRK fusion1
The benefit of VITRAKVI has been evaluated using a large population of patients with NTRK gene fusion cancer, in single-arm trials which enrolled patients with a wide range of different tumour types.1
High overall response rate with VITRAKVI in adult and paediatric patients with NTRK fusion cancer across a range of tumour types1
Overall response rate (ORR) of 79% in the expanded efficacy population of solid tumour types (n=153).*2
Adapted from VITRAKVI Summary of Product Characteristics.
Study Design: 192 adult and paediatric patients with TRK fusion cancer who had measurable disease assessed by RECIST v1.1, a non-CNS primary tumour, and received at least 1 dose of VITRAKVI were included for the pooled efficacy analysis across the multicentre, open-label, single-arm clinical studies: 1 (NCT02122913), 2 (NAVIGATE), and 3 (SCOUT).1
Major efficacy outcome measures: ORR and DoR, as determined by blinded IRC according to RECIST v1.1 for 192 patients and RANO only for some primary CNS tumour patients.1
a A pathological CR was a CR achieved by patients who were treated with VITRAKVI and subsequently underwent surgical resection with no viable tumour cells and negative margins on post-surgical pathological evaluation. The presurgical best response for these patients was reclassified pathological CR after surgery following RECIST v1.11
Overall response rate (ORR) of 67% in the pooled primary analysis population of solid tumour types (n=102).*1
Adapted from VITRAKVI EPAR public assessment report.
*The pooled primary analysis (n=102) included 93 patients with non-CNS primary tumours, and the post hoc addition of 9 patients with primary CNS tumours. Excluding patients with CNS tumours, ORR was 72% (95% CI: 62%, 81%).
Assessed in three clinical studies. Due to the rarity of TRK fusion positive cancer, patients were studied across multiple tumour types. The major efficacy endpoints were ORR and DOR, as determined by a BIRC. Due to the limited number of patients in some tumour types, there is uncertainty on the ORR estimate per tumour type. The ORR in the total population may not reflect the expected response in a specific tumour type.1
†Paediatric patient (6 months old at enrolment) with locally advanced
unresectable infantile fibrosarcoma with complete surgical response.
VITRAKVI shows evidence of a rapid and durable response with a median time to first response of 1.84 months (0.89, 16.20)1
In the analysis of the expanded efficacy population, the median duration of response was nearly three years (34.5 months) while the median time to response remained 1.84 months (range: 0.89–16.2).
mDoR: 34.5 months (range 1.6+ to 58.5+)
Adapted VITRAKVI Summary of Product Characteristics.
At the time of the primary analysis, the median time to first response was 1.84 months (range: 0.92, 14.55) and the median duration of response (mDoR) had not been reached.1
BIRC - assessed data. EMA press release 2019. First ‘histology-independent’ treatment for solid tumours with a specific gene mutation.
Adapted from VITRAKVI Summary of Product Characteristics.
67% (95% CI; 60,74) of patients achieved progression-free survival at 1 year with VITRAKVI1
Median progression free survival was 33.4 months at the time of the analysis, with a progression free survival rate of 67% [95% CI: 60, 74] after 1 year and 57% [95% CI: 49, 65] after 2 years.1
Adapted VITRAKVI Summary of Product Characteristics.
In the primary analysis (n=93), almost two-thirds of all patients remained progression free at one year.3 Median PFS had not been reached, with a median follow up of 12.1 months (range: 0.66 to 40.7 months).3
Adapted from European Assessment Report (EPAR) for Vitrakvi (larotrectinib), July 2019.
The primary analysis set consisted of 93 patients and did not include primary CNS tumours. 52% of patients had received VITRAKVI for 12 months or more and 30% had received VITRAKVI 18 months or more.3
The median change in tumour size in the pooled primary analysis set was a decrease of 70%.1
Maximum change in tumour size by tumour type in the enlarged efficacy population2
Adapted from Hong DS et al. Lancet Oncol 2020.
Disease assessment based on IRC using RECIST (version 1.1). The enlarged efficacy population (n=159) did not include primary CNS tumours. Analysis also excludes four patients who had clinical deterioration prior to an initial response assessment and six patients who were not evaluable due to insufficient time on therapy.2
The majority of patients in the pooled primary analysis set experienced a reduction in tumour size with VITRAKVI, with a median reduction in tumour size of 66%.3
Adapted from European Assessment Report (EPAR) for Vitrakvi (larotrectinub), July 2019
The median of the maximum decrease from baseline was -66.35% (Range: -100%, 41.2%) and median absolute change was -27.54 mm (Range: -201.7 mm, 25.0 mm).3
The pooled primary analysis set consisted of 93 patients and did not include primary CNS tumours.3
VITRAKVI ORR and DOR by tumour type (IRC analysis by RECIST 1.1)1
|
|
ORR |
DOR |
||||
|---|---|---|---|---|---|---|
|
Tumour type* |
Patients |
% |
95% CL |
≥12 months |
Range (months) |
|
|
Soft tissue sarcoma |
21 |
81% |
58%, 95% |
78% |
1.9+, 38.7+ |
|
|
Salivary gland |
17 |
88% |
64%, 99% |
91% |
3.7+, 33.7+ |
|
|
Infantile fibrosarcoma |
13 |
92% |
64%, 100% |
60% |
1.6+, 17.3+ |
|
|
Thyroid |
10 |
70% |
35%, 93% |
86% |
3.7, 29.8+ |
|
|
Primary CNS* |
9 |
11% |
0%, 48% |
NR |
2.0+ |
|
|
Lung |
7 |
71% |
29%, 96% |
75% |
7.4+, 25.8+ |
|
|
Melanoma |
7 |
43% |
10%, 82% |
50% |
1.9+, 23.2+ |
|
|
Colon |
6 |
33% |
4%, 78% |
NR |
5.6, 9.2+ |
|
|
GIST |
4 |
100% |
40%, 100% |
67% |
7.4+, 20.0+ |
|
|
Bone Sarcoma |
2 |
50% |
1%, 99% |
0% |
9.5 |
|
|
Cholangiocarcinoma |
2 |
SD, NE |
NA |
NA |
NA |
|
|
Congenital mesoblastic |
1 |
100% |
3%, 100% |
NR |
9.8+ |
|
|
Appendix |
1 |
SD |
NA |
NA |
NA |
|
|
Breast† |
1 |
PD |
NA |
NA |
NA |
|
|
Pancreas |
1 |
SD |
NA |
NA |
NA |
|
Adapted from VITRAKVI Summary of Product Characteristics.
*Patients with a primary CNS tumour were evaluated per investigator assessment using either RANO or RECIST v1.1 criteria.
†Non-secretory.
+Denotes ongoing response.
The benefit of VITRAKVI has been established in single arm trials encompassing a relatively small sample of patients whose tumours exhibit NTRK gene fusions. VITRAKVI should only be used if there are no treatment options for which clinical benefit has been established, or where such treatment options have been exhausted (i.e., no satisfactory treatment options).1
Improvements in QoL were reported for all tumour types included in this analysis,* and occurred by month 2 in most patients.4 Both adult and paediatric patients treated with VITRAKVI saw improvements in their quality of life.3, 4
Clinically meaningful improvements in QoL were reported by:3,4*
*Changes in EORTC-QLQ-C30 global health and PEDS-QL scores that reached or exceeded the minimally important difference were considered clinically meaningful. 10% of adult and 12% of paediatric patients also reported improvements in QoL that were not clinically meaningful.4
As of July 2018, 57 patients (40 adult, 17 paediatric) had completed EORTC-QLQ-C30 global health (adult) and PEDS-QL (paediatric) questionnaires at baseline and at least one post baseline timepoint.4
Analyses are based on small, open-label, single arm Phase II clinical studies (NAVIGATE, NCT02576431; SCOUT, NCT02637687) that are still ongoing; therefore the number of patients available is limited. However, results are consistent with the rapid onset clinical benefits and low rate of adverse events of VITRAKVI.4
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