In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 6081-6081
Abstract:
6081 Background: DTC comprises multiple histology subtypes, the most common being papillary and follicular. Based on results of the phase 3 COSMIC-311 trial, the multikinase inhibitor cabozantinib was recently approved by FDA for the treatment of pts with RAIR DTC who progressed after prior VEGFR-targeted therapy (Brose et al. 2021). In an extended follow-up, median (m) progression-free survival (PFS) was 11 months (mo) for cabozantinib vs 1.9 mo for placebo (HR 0.22, 96% CI 0.15–0.32, P 〈 .0001) in the intent-to-treat (ITT) population (Capdevila et al. ESMO 2021. Abstr LBA67). Here we present outcomes for prespecified subgroups based on the baseline histology subtypes of papillary and follicular thyroid cancers. Methods: Pts were randomized 2:1 to cabozantinib (60 mg QD) or placebo. Placebo pts could cross over to open-label cabozantinib upon disease progression per blinded independent radiology committee (BIRC). Primary endpoints were PFS (ITT) and objective response rate (ORR, first 100 randomized pts), per RECIST v1.1 assessed by BIRC. Results: After a median follow-up of 10.1 mo, 258 pts (170 cabozantinib, 88 placebo) had been randomized (data cutoff 8 Feb 2021); 150 pts (96 cabozantinib, 54 placebo) had papillary thyroid cancer (PTC) and 113 pts (78 cabozantinib, 35 placebo) had follicular thyroid cancer (FTC), with the PTC and FTC subgroups each including 5 pts with both PTC and FTC. Sixty-three pts (̃56%) within the FTC subgroup had Hurthle cell and poorly differentiated variants. mPFS was 9.2 mo for cabozantinib vs 1.9 mo for placebo in the PTC subgroup (HR 0.27, 95% CI 0.17–0.43) and 11.2 mo vs 2.6 mo in the FTC subgroup (HR 0.18, 95% CI 0.10–0.31). The mPFS was 11.1 mo for cabozantinib and 1.9 mo for placebo for pts with Hurthle cell and poorly differentiated variants (HR 0.12, 95% CI 0.05–0.27). The ORR was 15% for cabozantinib vs 0% for placebo in the PTC subgroup and 8% vs 0% in the FTC subgroup. Median duration of cabozantinib exposure was 5.5 mo for the PTC subgroup and 7.3 mo for FTC. Grade 3/4 treatment-emergent adverse events (TEAE) in the cabozantinib arm occurred in 59% of pts in the PTC subgroup and 68% of pts in the FTC subgroup; discontinuations due to TEAE occurred in 17% and 15% of pts, respectively. Conclusions: In the extended follow-up, cabozantinib maintained superior efficacy vs placebo irrespective of histology subtype, including the aggressive Hurthle cell and poorly differentiated variants. The moderately higher rates of grade 3/4 TEAE in the FTC vs the PTC subgroup could be attributed to the longer median duration of exposure of cabozantinib in the FTC subgroup. Clinical trial information: NCT03690388.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2022.40.16_suppl.6081
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2022
detail.hit.zdb_id:
2005181-5
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