Selpercatinib is indicated for locally advanced/metastatic RET-activated solid
tumors after progression or following prior systemic
therapies. Until the recently published data from LIBRETTO-431 and LIBRETTO-531, there were limited effectiveness data comparing
selpercatinib with other first-line treatments in RET-activated
non-small cell lung cancer (NSCLC),
medullary thyroid cancer (MTC), and
thyroid cancer (TC). This study analyzed patient data from LIBRETTO-001 and compared the outcomes (
time to treatment discontinuation {TTD}, time to next treatment or death {TTNT-D}, time to progression {
TTP}, and the objective response rate {ORR}) of first-line
selpercatinib (
selpercatinib arm) use with the outcomes of first-line standard
therapies in patients who then received
selpercatinib in later lines of treatment (comparator arm). Overall, the first-line
selpercatinib arm had a longer TTD, TTNT-D, and
TTP versus the first-line comparator arm. The hazard ratios (HRs) for TTD were 0.29 (NSCLC), 0.15 (MTC), 0.08 (TC); for TTNT-D, the HRs were 0.48 (NSCLC), 0.11 (MTC), 0.09 (TC); and for
TTP, the HRs were 0.54 (NSCLC), 0.15 (MTC), and 0.12 (TC). The ORR was higher for first-line
selpercatinib versus the first-line comparator (NSCLC: 85.3% vs. 39.7%; MTC: 82.6% vs. 15.2%; and TC: 81.8% vs. 31.8%). First-line
selpercatinib use is associated with improved outcomes compared to first-line comparator
therapies for patients with advanced/metastatic RET-activated
cancers.