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Pralsetinib Shows Robust Activity in Patients with RET-Altered Medullary Thyroid Cancer

Pralsetinib had activity across all RET alterations and regardless of whether the RET mutation was somatic or germline
20 Sep 2020
Anticancer agents & Biologic therapy;  Endocrine and neuroendocrine tumours;  Personalised medicine

Promising results were shown with pralsetinib (BLU-667) in patients with advanced RET mutation-positive medullary thyroid cancer (MTC) that included high rates of durable response and disease control, as well as high 18-month rates of progression-free survival (PFS). These findings supporting the registration of pralsetinib in RET-positive MTC were reported by Prof. Mimi Hu of the Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center in Houston, USA at the ESMO Virtual Congress 2020.

Prof. Hu presented the registrational data observed with pralsetinib, a highly potent, selective RET inhibitor targeting oncogenic RET alterations, in patients with RET-positive MTC participating in the ARROW study.

The ARROW study is ongoing and is conducted at 85 sites in 13 countries. The study consists of a phase I dose escalation that determined the recommended phase II pralsetinib dose as 400 mg orally once daily, and phase II expansion cohorts defined by RET-altered tumour type and/or treatment history.

Primary objectives in phase II included overall response rate (ORR) and duration of response (DoR) by blinded independent central review per RECIST v1.1 and safety.

At ESMO 2020, efficacy findings were presented for response-evaluable patients with RET-positive MTC and safety for all patients across RET-altered tumour types receiving oral pralsetinib at 400 mg daily.

The ORR was greatest in treatment-naive patients

As of the data cut-off date of 13 February 2020, ninety-two patients with RET-positive MTC were enrolled by 11 July 2019; of these, 61% had M918T, 29% had cysteine rich domain, 3% had V804X and 7% of patients had other RET mutations.

In 53 evaluable patients previously treated with cabozantinib and/or vandetanib, the ORR was 60% (95% confidence interval [CI] 46–74), which included 2% complete responses (CR) and 58% partial responses (PR) (1 pending). The disease control rate (DCR) was 96% (95% CI 87-100).

In 19 evaluable, treatment-naïve patients, the ORR was 74% (95% CI 49–91), including 5% CR and 68% PR (all confirmed). The DCR was 100% (95% CI 82-100).


A: Clinical response to pralsetinib in patients with prior cabozantinib and/or vandetanib treatment;
B: Clinical response to pralsetinib in patients with no prior systemic treatment.

© Mimi Hu.

Responses were observed in patients with both somatic or germline RET genotypes, including 5 of 6 patients with V804X gatekeeper mutation.

Neither median PFS nor DoR were reached.

In patients previously treated with cabozantinib or vandetanib, 94% of responders remained on treatment. In systemic treatment-naïve patients, 93% of responders remained on treatment.

Pralsetinib was well-tolerated with mostly Grade 1/2 treatment-related adverse events reported

The safety population comprised of 438 patients; treatment-related adverse events (TRAEs) were primarily Grade 1–2. The most frequently reported any Grade TRAEs consisted of increased aspartate aminotransferase (34%), anaemia (24%), increased alanine aminotransferase (23%), constipation (23%) and hypertension (22%).

A total of 4% of patients discontinued treatment due to TRAEs.


Based on these results, the authors concluded that pralsetinib demonstrated potent and durable clinical activity in advanced RET mutation-positive medullary thyroid cancer regardless of prior treatment with approved multikinase inhibitors or RET-mutation genotype and was well tolerated.

The study was funded by Blueprint Medicines Corporation.


1913O – Hu M, Subbiah V, Wirth LJ, et al. Results from the registrational phase I/II ARROW trial of pralsetinib (BLU-667) in patients (pts) with advanced RET mutation-positive medullary thyroid cancer (RET+ MTC). ESMO Virtual Congress 2020.

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