Dataset Information

Efficacy of Selpercatinib in RET-Altered Thyroid Cancers.

ABSTRACT:

Background

RET mutations occur in 70% of medullary thyroid cancers, and RET fusions occur rarely in other thyroid cancers. In patients with RET-altered thyroid cancers, the efficacy and safety of selective RET inhibition are unknown.

Methods

We enrolled patients with RET-mutant medullary thyroid cancer with or without previous vandetanib or cabozantinib treatment, as well as those with previously treated RET fusion-positive thyroid cancer, in a phase 1-2 trial of selpercatinib. The primary end point was an objective response (a complete or partial response), as determined by an independent review committee. Secondary end points included the duration of response, progression-free survival, and safety.

Results

In the first 55 consecutively enrolled patients with RET-mutant medullary thyroid cancer who had previously received vandetanib, cabozantinib, or both, the percentage who had a response was 69% (95% confidence interval [CI], 55 to 81), and 1-year progression-free survival was 82% (95% CI, 69 to 90). In 88 patients with RET-mutant medullary thyroid cancer who had not previously received vandetanib or cabozantinib, the percentage who had a response was 73% (95% CI, 62 to 82), and 1-year progression-free survival was 92% (95% CI, 82 to 97). In 19 patients with previously treated RET fusion-positive thyroid cancer, the percentage who had a response was 79% (95% CI, 54 to 94), and 1-year progression-free survival was 64% (95% CI, 37 to 82). The most common adverse events of grade 3 or higher were hypertension (in 21% of the patients), increased alanine aminotransferase level (in 11%), increased aspartate aminotransferase level (in 9%), hyponatremia (in 8%), and diarrhea (in 6%). Of all 531 patients treated, 12 (2%) discontinued selpercatinib owing to drug-related adverse events.

Conclusions

In this phase 1-2 trial, selpercatinib showed durable efficacy with mainly low-grade toxic effects in patients with medullary thyroid cancer with and without previous vandetanib or cabozantinib treatment. (Funded by Loxo Oncology and others; LIBRETTO-001 ClinicalTrials.gov number, NCT03157128.).

SUBMITTER: Wirth LJ

PROVIDER: S-EPMC10777663 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Efficacy of Selpercatinib in <i>RET</i>-Altered Thyroid Cancers.

Wirth Lori J LJ Sherman Eric E Robinson Bruce B Solomon Benjamin B Kang Hyunseok H Lorch Jochen J Worden Francis F Brose Marcia M Patel Jyoti J Leboulleux Sophie S Godbert Yann Y Barlesi Fabrice F Morris John C JC Owonikoko Taofeek K TK Tan Daniel S W DSW Gautschi Oliver O Weiss Jared J de la Fouchardière Christelle C Burkard Mark E ME Laskin Janessa J Taylor Matthew H MH Kroiss Matthias M Medioni Jacques J Goldman Jonathan W JW Bauer Todd M TM Levy Benjamin B Zhu Viola W VW Lakhani Nehal N Moreno Victor V Ebata Kevin K Nguyen Michele M Heirich Dana D Zhu Edward Y EY Huang Xin X Yang Luxi L Kherani Jennifer J Rothenberg S Michael SM Drilon Alexander A Subbiah Vivek V Shah Manisha H MH Cabanillas Maria E ME

The New England journal of medicine 20200801 9

<h4>Background</h4><i>RET</i> mutations occur in 70% of medullary thyroid cancers, and <i>RET</i> fusions occur rarely in other thyroid cancers. In patients with <i>RET</i>-altered thyroid cancers, the efficacy and safety of selective RET inhibition are unknown.<h4>Methods</h4>We enrolled patients with <i>RET</i>-mutant medullary thyroid cancer with or without previous vandetanib or cabozantinib treatment, as well as those with previously treated <i>RET</i> fusion-positive thyroid cancer, in a p ...[more]

PMID: 32846061

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