LIBRETTO-431 Analysis: Selpercatinib May Have CNS Protective Effect in RET-Fusion Positive NSCLC

Selpercatinib may help prevent or delay the formation of new central nervous system (CNS) metastases in patients with advanced non-small cell lung cancer (NSCLC), specifically those with RET fusions, compared with chemotherapy plus pembrolizumab, according to a recent study published in the Journal of Clinical Oncology.

Maurice Pérol, MD, of the Centre Léon Bérard, and colleagues examined CNS scans from LIBRETTO-431, a phase 3 clinical trial that compared first-line selpercatinib with chemotherapy plus pembrolizumab in RET-fusion positive NSCLC.

MRI was used to perform intracranial scans for 69% of patients in the selpercatinib arm and 57% of patients in the control arm. At baseline, 150 patients of 192 did not have CNS metastases. Furthermore, there was a lower proportion of patients with baseline CNS metastases in the selpercatinib arm versus the control arm (17.5% v 29.2%, respectively).

In the patients without CNS metastases, the 12-month cumulative incidence rate of CNS progression was 1.1% with selpercatinib compared with 14.7% in those in the control arm.  Moreover, the 12-month intracranial progression-free survival (PFS) rate was 91.8% in the selpercatinib arm versus 74.7% in the control arm. The hazard ratio for intracranial PFS was .46.

Similar trends were observed in the cumulative incidence rate of CNS progression and intracranial PFS in the 42 patients with CNS metastases. The 12-month cumulative incidence rate of CNS progression was 25.7% with selpercatinib compared with 33.3% in the control arm. The 12-month intracranial PFS rate was 63.9% with selpercatinib versus 56.1% with chemotherapy/pembrolizumab.

“These data supplement the primary LIBRETTO-431 report to further demonstrate that selpercatinib may prevent the formation of new CNS metastases in addition to treating existing CNS metastases,” the researchers said.

However, several limitations including short follow-up time, small number of events, and low number of evaluable patients in certain subgroups, mean that longer follow-up is required to confirm intracranial efficacy with selpercatinib.

This study is of importance because it reinforces how crucial it is to identify RET fusions in first-line patients with NSCLC and subsequently treating them with selpercatinib, the researchers said.

Source: Journal of Clinical Oncology