Sustained improvements in quality of life with larotrectinib

In the majority of adults, children, and infants with TRK-fusion cancer, treatment with larotrectinib induces rapid, sustained, and clinically meaningful improvements in quality of life.

Larotrectinib is a highly selective TRK inhibitor that is approved to treat adult and paediatric patients with solid tumours harbouring an NTRK gene-fusion. In clinical trials, larotrectinib demonstrated a 79% objective response rate and over 35 months median duration of response, regardless of tumour type and age [1]. The drug was well tolerated with mainly grade 1 or 2 adverse events.

To get more insight in the efficacy of larotrectinib on quality of life, quality of life outcomes were analysed from an expanded dataset of adults, children, and infants with TRK fusion cancer treated with larotrectinib in 2 ongoing trials: a phase 2 basket trial in adults and adolescents (NAVIGATE) and a single-arm phase 1/2 trial in paediatric patients (SCOUT). Patients completed validated quality of life questionnaires at baseline and at planned cycle visits. In the case of younger children and infants, the questionnaires were completed by their parents. Best changes in scores from baseline and during treatment were compared to the Minimally Important Difference (MID), which is the smallest difference in score that patients perceive as beneficial or detrimental [2]. At data cut-off, 126 patients (74 adults, 24 children ≥2 years of age, and 28 infants ≤2 years of age) had received larotrectinib and completed baseline and at least one post-baseline questionnaire.

At baseline, 70% of the adults reported a normal or above normal quality of life. During treatment with larotrectinib, 98% of these patients remained in that category. For 91% patients who reported quality of life below normal at baseline, treatment with larotrectinib led to quality of life improvement. Reported improvement reached or exceeded the MID in 59% of patients. MID improvements were reported for most tumour types. Of note, all 10 patients with brain metastases had clinically meaningful improvements in quality of life.

Similarly, at baseline, 38% of children ≥2 years reported a normal or above normal quality of life; in all of these children, quality of life remained normal/above normal during treatment with larotrectinib. Treatment with larotrectinib improved quality of life in 67% of the children ≥2 years who reported quality of life below normal at baseline. A total of 88% of the children had quality of life improvements, in 79% reaching or exceeding the MID, also across tumour types.

A categorisation analysis for infants ≤2 years of age was not possible, as there is no accepted normal range for this group. General quality of life improvement during treatment with larotrectinib was reported in 82% of the infant patients, with MID improvements reported in 57%, again observed across all tumour types.

Among evaluable patients, 47% of adults, 75% of children, and 43% of infants had quality of life improvements that lasted for at least 2 consecutive cycles. The onset of these sustained quality of life improvements were rapid, occurring by 2 months of treatment in 69% of adults, 75% of children, and 61% of infants. The median duration of the quality of life improvements was 12 months in adults and not estimable in children and infants.

1. Hong DS, et al. Lancet Oncol. 2020;21: 531-540.
2. Kummar S, et al. ASCO Virtual Meeting, 29-31 May 2020, Abstract 3614

Posted on 9 September 202019 September 2020