Selpercatinib Superior to Prior Systemic Therapy in RET-Positive NSCLC

According to data from the phase 1/2 LIBRETTO-001 trial, selpercatinib demonstrated superior clinical benefit over prior systemic therapies in patients with RET+ non-small-cell lung cancer (NSCLC; Journal of Clinical Oncology 9032-9032.). 

"Selpercatinib is a first-in-class highly selective, potent, CNS-active RET kinase inhibitor, is approved in multiple countries for treatment of [RET+] lung or thyroid cancers," explained Alexander E. Drilon, MD, Memorial Sloan Kettering Cancer Center, New York, and colleagues. 

The LIBRETTO-001 trial is a global, multi-center trial that enrolled RET+ NSCLC patients across 16 countries and 89 sites. The primary endpoint was objective response rate (ORR), secondary endpoints included progression-free survival (PFS), duration of response, and safety. Results from this analysis were based on data from a March 2020 cutoff date. 

The physician-reported best overall response (BOR) from the last systemic therapy received before study enrollment was compared with selpercatinib BOR by an independent review committee per RECIST v1.1. Each patient served as their own control.

Of the 218 patients evaluated, the median number of prior system therapies was 2. Altogether, 57% of patients responded to selpercatinib, and 16% responded to immediate prior therapy. ORR improved with selpercatinib, regardless of prior therapy: chemotherapy + immune checkpoint inhibitor (ICI) (57% vs 14%), single-agent ICI (48% vs 3%), or chemotherapy (58% vs 15%).

Furthermore, 49% (n = 108) patients responded to selpercatinib but not to immediate prior therapies. Meanwhile, 2% of patients who received selpercatinib had progressive disease as their BOR, compared to 28% in those who received immediate prior therapy. The median duration of therapy for selpercatinib and immediate prior therapy was 11.8 months vs. 3.4 months, respectively. 

‘“In patients with RET+ NSCLC treated on LIBRETTO-001, systemic therapies administered prior to enrollment achieved less meaningful clinical benefit than selpercatinib. Selpercatinib demonstrated consistent efficacy regardless of the type of prior therapy,” concluded Dr Drilon et al.—Alexandra Graziano