What is the cure rate of Larotinib/Larotinib?

Larotrectinib is a highly selective central nervous system (CNS) active tropomyosin receptor kinase (TRK) inhibitor approved for the treatment of adult and pediatric patients with TRK fusion cancer. In a comprehensive analysis of 206 patients with non-primary CNS TRK fusion cancers, investigators assessed larotrectinib's objective response rate (ORR) to be 75%; median progression-free survival (PFS) to be 35.4 months.

Collected data from three clinical trials (NCT02576431, NCT02122913 and NCT02637687) of larotrectinib in patients with non-primary CNS-TRK fusion cancers. Larotrectinib was continued until disease progression, discontinuation, or unacceptable toxicity. ORR was assessed by an independent review committee (IRC) according to RECIST v1.1. As of the data show, 244 of 269 patients treated with larotrectinib can be evaluated for efficacy by IRC. There are 25 different tumor types. The most common were soft tissue sarcomas (STS [43%], including infantile fibrosarcoma [18%] and other STS [25%]), thyroid (11%), lung (10%), salivary glands (9%), and colorectum (7% [colon, n = 18; rectum, n = 1]). 94 (35%) patients were <18 years old; 175 (65%) were ≥18 years old. Pts had gene fusions involving NTRK1 (46%), NTRK2 (3%), or NTRK3 (51%).

A total of27%, 28%, and 45% of subjects had 0, 1, and ≥ 2 prior systemic treatments, respectively. The ORR was 69% (95% confidence interval [CI] 63-75): 64 (26%) complete responses (CR), including 13 (5%) pathological CR, 104 (43%) partial response, 41 (17%) stable disease, 20 (8%) progressive disease, and 15 (6%) undetermined. Median response time was 1.8 months (range 0.9-16.2). The median duration of response (DoR) was 32.9 months (95% CI, 27.3-41.7); the median follow-up time was 28.3 months. Median PFS was 29.4 months (95% CI 19.3-34.3); median follow-up was 29.3 months. At a median follow-up of 32.2 months, the median overall survival (OS) was not reached; the 48-month OS incidence rate was 64% (95% CI 55-73). Treatment duration ranged from 0.1 to 67.9 months. .

Treatment-related adverse events (TRAEs) were primarily grade 1-2; 50 (20%) patients had grade 3-4 TRAEs. Five (2%) patients discontinued treatment due to TRAEs. In order to eliminate the possible confounding effect of continued enrollment on the median DoR, exploratory analysis was conducted on the data. ORR was 74% (95%CI, 67-81), median DoR was 34.5 months (95%CI 27.6–43.3); median follow-up time was 34.1 months.

With extended follow-up, larotrectinib continued to demonstrate rapid and durable responses, prolonged survival benefit, and a favorable safety profile. These results highlight the importance of detecting NTRK gene fusions in cancer patients. However, the definition of complete cure is very strict in cancer treatment. It means that the tumor has completely disappeared and will never recur or metastasize. Current data are insufficient to determine whether larotrectinib achieves this complete cure in all patients. Some patients may develop drug resistance or disease progression, especially with long-term use.