RET-Targeted Lung Cancer Drugs Pralsetinib and Selpercatinib: Difficult to Compare Directly

An analysis found that it is difficult to directly compare the first-line treatment effects of pralsetinib and selpercatinib, which are used to treat RET (rearranged during transfection) fusion-positive advanced non-small cell lung cancer. The hazard ratios (HRs) for the two drugs were essentially similar.

According to a report published on the 30th (local time) by Chinese biotech news outlet BioOn, the drugs reduced the risk of disease progression or death by about 49% and 47%, respectively, compared with standard treatment in their respective phase 3 clinical trials.

In the AcceleRET-Lung study of pralsetinib, median progression-free survival (PFS) by investigator assessment was 18.7 months in the treatment group and 7.2 months in the control group. The HR was 0.51 (95% confidence interval, 0.34~0.77).

In the LIBRETTO-431 study of selpercatinib, median PFS was 24.8 months in the treatment group and 14.0 months in the control group, with an HR of 0.53 (95% confidence interval, 0.34~0.80).

The absolute median PFS values from the two studies do not provide a basis for direct comparison. Median PFS was longer in both the treatment and control groups in the selpercatinib study, which may be because that study included more patients with a relatively favorable prognosis.

Differences in study design also had an effect. AcceleRET-Lung included patients with both squamous and nonsquamous cell carcinoma, whereas LIBRETTO-431 enrolled only patients with nonsquamous cell carcinoma.

By contrast, the HR compares the two groups randomized within each study. Pralsetinib’s HR of 0.51 means that the rate of disease progression or death was about 51% that of the control group, corresponding to an approximately 49% reduction in risk. Selpercatinib, with an HR of 0.53, showed an approximately 47% reduction in risk.

Overall, the HRs for the two drugs were nearly identical, with pralsetinib slightly ahead numerically. However, it is difficult to determine which is superior because the control groups used as comparators differed.

Results for the full randomized population in the pralsetinib study were also released. AcceleRET-Lung randomized a total of 223 patients and was terminated early by the original developer on January 27, 2025. In the full population, median PFS was 18.7 months in the treatment group and 9.0 months in the standard-treatment group, with an HR of 0.59 (95% confidence interval, 0.42~0.84).