Cutting-edge medical technology: Latest medical research results and applications of larotrectinib

Based on results of a match-adjusted indirect comparison (MAIC) using real-world data presented at the 2022ASCO annual meeting to standard of care (SOCTRK) fusion-positive cancers had longer overall survival when treated with the TRK inhibitor larotrectinib than pan>.

MAIC is a common method of balancing patient population characteristics, allowing cross-study comparisons in the absence of individual patient data. MAICNeeds evaluationThe efficacy of larotrectinibin this patient population is due to neurotrophicTRK(NTRK) fusions are rare in patients, meaning single-arm trials evaluating larotrectinib are limited in comparing its effectiveness with the SOC regimen.

In their MAIC OSanalysis, the researchers found that with SOC (n = 28), patients who received larotrectinib had a 78% lower risk of death, with a pre-weighted hazard ratio of 0.09 but an adjusted hazard ratio of 0.22 (95%). CI, 0.09-0.52; P = .001). Additionally, after weighting, the median OS for patients treated with larotrectinib was 39.7 months compared with 10.2 months for those treated with SOC.

The researchers created 2 study cohorts by looking at a previous analysis from the European Society of Medical Oncology that identified NTRK fusion-positive patients who were not treated with TRK inhibitors and were treated with / from Flatiron HealthData from the Basic Medicine Clinical Genome Database were used as the SOC cohort.

The researchers then usedMAIC to compare larotrectinib and SOC by balancing various population characteristics across several studies. Patient-level data were collected from clinical trials of TRK inhibitors: a Phase 1 trial (NCT02122913), S The COUT trial (NCT02637687) and the NAVIGATE trial (NCT02576431). They then aggregated the SOC data by matching individual data to common baseline characteristics.

To assess whether the two groups were similar before starting larotrectinib, a log-rank test was performed and found no difference between the two groups (P = .31). Thereafter, larotrectinib versus SOC was evaluated for the treatment of OS.

To evaluate the OS results with more certainty, the researchers also conducted 2 sensitivity analyses, because MAICToo many matching variables will reduce the effective sample size (ess), and the larotrectinib follow-up time is longer than the SOC follow-up time.

To account for the high degree of uncertainty in the base case analysis, they conducted several analyses, relaxing missing data assumptions and removing variables with minimal overlap between studies. Compared with the base case, ESS was 13.1, and HR was 0.22 pan>, when looking at missing values in prior treatment lines and patient ECOG performance scores, ESS was 23.6, HR is 0.10 (95% CI is 0.04-0.22). Then excluding patients with unknown primary (CUP) tumors and breast cancer, the ESS was 26.4 (HR, 0.10;95%confidence interval is 0.05-0.21), after excluding colorectal cancer patients, the ESS score is 37.9 ( pan>HR is 0.12; 95% confidence interval, 0.05-0.26), excluding patients with salivary gland cancer, ESS at 38.6 (HR, 0.12; 95% confidence interval is 0.05-0.25).

A restricted mean survival time analysis of up to 30.5 months was also performed, which was the minimum of the longest observed time to event within the SOC group. The researchers found that larotrectinib had an estimated mean survival advantage of 10.8 months compared with SOC (95% CI, 7-14.6; P < .01). On average, this means that potential patients who received larotrectinib would have lived 10.8 months longer at 30.5 months of follow-up compared with SOC. However, the researchers wrote in their poster that the analysis presented at ASCO is conservative and that the average benefit may continue to increase as patients are followed over time.

After adjustment82%of patients had positive fusions for NTRK1 in both arms39.3%of patients in the trial were 65 years old or older. In both groups, ECOG performance scores were 0-1 and 2-4SOC group, including uterus (4%), biliary tract (4%< /span>), stomach (4%), endometrium (4%), cup ( 4%), breast (4%), salivary gland (7%), non-small cell lung cancer (18%), soft tissue sarcoma (21%), and colorectal cancer (32%). There were no cases of uterine, biliary, gastric or endometrial cancer in the larotrectinib group.

When matching the number of lines of therapy since diagnosis, 71.4%of patients had received 0-2 lines of therapy since diagnosis, and 28.6%of patients had received 3 or more lines of therapy since diagnosis. The majority of patients (64.3%) had III or IV at initial diagnosis stage disease, of which 17.9% of patients were initially diagnosed with stage 0 to II disease. Most patients also have no or no brain metastases.