Dataset Information

Efficacy and safety of selpercatinib in Chinese patients with advanced RET-altered thyroid cancers: results from the phase II LIBRETTO-321 study.

ABSTRACT:

Background

Selpercatinib, a highly selective and potent REarranged during Transfection (RET) kinase inhibitor, is effective in advanced RET-altered thyroid cancer (TC). However, the efficacy and safety in Chinese patients are unknown.

Patients and methods

In the open-label, multi-center phase II LIBRETTO-321 (NCT04280081) study, Chinese patients with advanced solid tumors harboring RET alterations received selpercatinib 160 mg twice daily. The primary endpoint was objective response rate (ORR; RECIST v1.1) by independent review committee (IRC). Secondary endpoints included duration of response (DoR) and safety. Efficacy was assessed in the primary analysis set [PAS; treated patients with RET fusion-positive TC or RET-mutant medullary TC (MTC) confirmed by central laboratory] and all enrolled patients with MTC.

Results

Of 77 enrolled patients, 29 had RET-mutant MTC and one had RET fusion-positive TC. In the PAS (n = 26), the ORR by IRC was 57.7% [95% confidence interval (CI), 36.9-76.6]. Median DoR was not reached and 93.3% of responses were ongoing at a median follow-up of 8.7 months. In all enrolled MTC patients (n = 29), the ORR by IRC was 58.6% (95% CI, 38.9-76.5). One RET fusion-positive TC patient treated for 23.4 weeks achieved a partial response at week 8 that was ongoing at cutoff. In the safety population (n = 77), 59.7% experienced grade ⩾3 treatment-emergent adverse events (TEAEs). TEAEs led to dose reductions in 32.5% (n = 25) and discontinuations in 5.2% [n = 4; 3.9% (n = 3) considered treatment related] of patients.

Conclusions

Selpercatinib showed robust antitumor activity and was well tolerated in Chinese patients with advanced RET-altered TC, consistent with global data from LIBRETTO-001 (NCT04280081).

Clinicaltrialsgov identifier

NCT04280081 (first posted Feb 21, 2020).

SUBMITTER: Zheng X

PROVIDER: S-EPMC9434679 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Efficacy and safety of selpercatinib in Chinese patients with advanced <i>RET</i>-altered thyroid cancers: results from the phase II LIBRETTO-321 study.

Zheng Xiangqian X Ji Qinghai Q Sun Yuping Y Ge Minghua M Zhang Bin B Cheng Ying Y Lei Shangtong S Shi Feng F Guo Ye Y Li Linfa L Chen Lu L Shao Jingxin J Zhang Wanli W Gao Ming M

Therapeutic advances in medical oncology 20220829

<h4>Background</h4>Selpercatinib, a highly selective and potent REarranged during Transfection (RET) kinase inhibitor, is effective in advanced <i>RET</i>-altered thyroid cancer (TC). However, the efficacy and safety in Chinese patients are unknown.<h4>Patients and methods</h4>In the open-label, multi-center phase II LIBRETTO-321 (NCT04280081) study, Chinese patients with advanced solid tumors harboring <i>RET</i> alterations received selpercatinib 160 mg twice daily. The primary endpoint was ob ...[more]

PMID: 36062046

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Project description:BackgroundRET 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.MethodsWe 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.ResultsIn 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.ConclusionsIn 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.).

Project description:BackgroundPatient-reported outcomes (PROs) are increasingly becoming an important part of clinical trials as they are helpful in analyzing the safety and efficacy of treatment in chronic diseases like cancer.ObjectivesWe report PROs and health-related quality of life (HRQoL) with selpercatinib treatment among Chinese patients with rearranged in transfection (RET) fusion-positive non-small-cell lung cancer (NSCLC), RET fusion-positive thyroid cancer (TC), and RET-mutant medullary TC (MTC) as an exploratory analysis of the LIBRETTO-321 trial.DesignA total of 77 patients (47 RET fusion-positive NSCLC, 1 RET fusion-positive TC, and 29 RET-mutant MTC) were enrolled. Compliance for European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) was 100% at baseline and >90% at each time point.MethodsPROs were assessed using the EORTC QLQ-C30, and a bowel diary assessment for MTC patients with baseline diarrhea using the Systemic Therapy-Induced Diarrhea Assessment Tool. Data were collected at pre-dose; every 8 weeks from cycle 3; and every 12 weeks after cycle 13. A >10-point change from baseline was considered clinically meaningful. PRO changes were summarized through cycle 13.ResultsMost patients with NSCLC or MTC showed improvement or remained stable on the global health status and functional subscales. For global health status, 47.4% of NSCLC and MTC patients showed definite improvement with only 19.7% showing definite worsening. For functional subscales, less than 30% of the patients showed definite worsening. For symptom subscales, more than 64% of the patients either improved or remained stable for the symptoms. For MTC patients with bowel diary assessment (n = 5), there was no severity or worsening from baseline in the diarrheal episodes observed during treatment with selpercatinib.ConclusionThe study demonstrated favorable PROs in Chinese patients with RET fusion-positive NSCLC, TC, and RET-mutant MTC treated with selpercatinib. HRQoL was improved or stable as assessed by EORTC QLQ-30.Trail registrationThis study was registered at ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT04280081) ClinicalTrials.gov Identifier: NCT04280081.