Outcomes of Larotrectinib by Prior Therapy and Performance Status in TRK Fusion Cancer

In a poster presented at the American Association for Cancer Research (AACR) Annual Virtual Meeting 2020, held from April 27-28, 2020, researchers reported outcomes by the number of lines of priory therapy or baseline status in patients with TRK fusion cancer who were administered larotrectinib (Vitrakvi).¹

Ultimately, response rates were found to be highest in patients who were treatment naïve or who had an ECOG performance status of 0. However, larotrectinib was found to benefit patients across varying degrees of pretreatment or performance status.

“Larotrectinib is a highly selective TRK inhibitor that achieves an objective response rate of approximately 80% and a median duration of response of almost 3 years in patients with TRK fusion positive cancers of various histologies and ages,” Alexander Drilon, MD, of Memorial Sloan Kettering Cancer Center, said during a poster presentation at AACR.²

Overall, the researchers analyzed pooled data from 159 patients enrolled in 3 larotrectinib trials to assess outcomes stratified by prior lines of therapy and ECOG performance status. The trials included an adult phase I trial, a pediatric phase I/II trial, and an adult/adolescent phase II basket trial. 

“Clinical pathologic characteristics reflect the wide variety of pediatric and adult tumors that were treated with no significant differences between subpopulations and overall demographics,” Drilon explained.

Moreover, a post hoc analysis of overall response rates (ORR), assessed by investigators using Response Evaluation Criteria in Solid Tumors 1.1, duration of response (DOR), progression-free survival (PFS), and overall survival (OS) was performed. The data cut-off was February 19, 2019. 

“The median for each of these outcomes were not reached in several subpopulations, and even in patients who were heavily pretreated with 3 or more prior lines of therapy, the median duration of response, progression-free survival, and overall survival were impressive at 35 months, 28 months, and 44 months, respectively,” said Drilon. 

Of the total cohort, 35 patients had no prior lines of therapy, 48 had 1 prior line of therapy, 34 had 2 prior lines of therapy, and 42 had 3 or more prior lines of therapy. The cohort’s ORR was found to be highest at 0 lines of prior therapy (91%; 95% CI, 76-98), with the overall ORR being 79% (95% CI, 72-85). 

With regard to ECOG performance status, 76 patients had a score of 0, 61 had a score of 1, 19 had a score of 2, and 3 had a score of 3. The ORR generally appeared to decrease as the ECOG performance status increased, with those having a score of 0 also having the highest ORR of 91% (95% CI, 81-96). Further, the total ORR was 79% (95% CI, 72-85). 

“This observation is unsurprising, given the poor performance status represents an integrated metric of other poorly prognostic factors for any systemic therapies, such as increasing age and the number of comorbidities,” Drilon said. 

Notably, the safety profile of larotrectinib was compared across prior treatment lines and ECOG subgroups. The incidence of grade 3 and 4 adverse events was found to be similar across lines of therapy. 

Larotrectinib is currently approved for use in the United States, Canada, Europe, and Brazil, and researchers continue to explore the drug in ongoing clinical trials. 

References:

1. AACR. CT199 - Larotrectinib in TRK fusion cancer patients: Outcomes by prior therapy and performance status. AACR website. Published April 27, 2020. abstractsonline.com/pp8/#!/9045/presentation/10700. Accessed April 28, 2020. 

2. AACR. CT199 - Larotrectinib in TRK fusion cancer patients: Outcomes by prior therapy and performance status. AACR website. Published April 27, 2020. aacr20.onlineeventpro.freeman.com/posters/24211317/Larotrectinib-in-TRK-fusion-cancer-patients-Outcomes-by-prior-therapy-and-performance-status. Accessed April 28, 2020.