Selpercatinib Effective in RET Fusion–Positive NSCLC, Irrespective of Prior Therapies

Treatment with selpercatinib (Retevmo) demonstrated consistent efficacy in patients with RET fusion-positive non-small cell lung cancer (NSCLC), regardless of prior treatments, according to findings from the LIBRETTO-001 trial (NCT03157128) presented at the virtual 2021 ASCO Annual Meeting.

“(The) results, (however), should be interpreted with caution, as a limitation of this analysis was that immediate prior response assessment was based on physician-reported best response in patients’ medical history and may not follow RECIST criteria,” the study authors wrote in the poster.

The study was conducted across 89 sites in 16 countries and consisted of 218 evaluable patients (median age, 61 years) who previously received platinum-based chemotherapy. Most patients had an ECOG score of 0/1 (37%/61%) and received a median of 2 (range, 1-15) prior systematic therapies. The study’s primary endpoint was objective response rate (ORR), with additional endpoints of progression-free survival (PFS), duration of response (DOR) and safety.

The study compared physician reported best overall response (BOR) from last systematic therapy received prior to enrollment with selpercatinib BOR by independent review committee, and each patient served as their own control.

The ORR with selpercatinib was 57% which was “markedly higher,” the authors wrote, than responses with prior treatment which was 16%.

A total of 108 patients (50%) did not respond to prior therapy but responded to treatment with selpercatinib. There were 16 patients (7%) who responded to both selpercatinib and prior therapy, 18 patients (8%) who responded to prior therapy but not selpercatinib and 76 patients (35%) who did not respond to either.

ORR was improved regardless of prior therapy, chemotherapy plus immune checkpoint inhibitor (ICI) (57% versus 14%), single-agent ICI (48% versus 3%) or chemotherapy (58% versus 15%).

Fewer patients had progressive disease with selprecatinib BOR (2%), compared with immediate prior therapy (28%). Median DOR was also notably longer compared with prior therapy, 11.8 months versus 3.4 months.

The authors concluded noting that the global, randomized phase 3 LIBRETTO-431 trial (NCT04194944) evaluating selpercatinib compared with standard frontline therapy (pemetrexed/carboplatin with or without pembrolizumab [Keytruda]) is ongoing.

Reference

1. Drilon A, Gautschi O, Besse B, et al. Response to selpercatinib versus prior systematic therapy in patients (pts) with RET fusion + non-small cell lung cancer (NSCLC). J Clin Oncol. 2021;39(suppl 15):Abstract 9032.