Background

Medullary thyroid cancer (MTC) standard of care includes multikinase inhibitors (MKIs), which can exacerbate disease-related diarrhea, primarily due to non-RET kinase inhibition. We report diarrhea and other patient reported-outcomes (PROs) with selpercatinib, a highly selective RET inhibitor, among patients with RET-mutant MTC in the ongoing, phase 1/2 LIBRETTO-001 trial.

Materials and Methods

Instrument completion timepoints were baseline (Cycle 1, Day 1) and approximately every other 28-day cycle until Cycle 13 (every 12 weeks thereafter) for EORTC QLQ-C30, and baseline, weekly during Cycle 1, and Day 1 of every cycle for mSTIDAT. A ≥10-point change from baseline in domain score was considered clinically meaningful. PROs were summarized through Cycle 13 in all patients and by subgroups with or without prior exposure to MKIs vandetanib and/or cabozantinib (V/C).

Results

Among the overall MTC population (n=226), 88 (39%) and 124 (55%) patients comprised the V/C-naïve and previous V/C subgroups, respectively. Compliance was >85% for both instruments at each timepoint. Most patients maintained/improved in all HRQoL subscales throughout treatment. Improvements in diarrhea were clinically meaningful in 43.5% of patients overall and in 36.8% and 51.3% of V/C-naïve and previous V/C subgroups, respectively. At baseline, 80.4% of all patients reported diarrhea on mSTIDAT. The percentage of patients who reported diarrhea was reduced to less than half of all patients (range: 33.3%-48.3%) after Cycle 2.

Conclusion

These interim results demonstrate that patients with RET-mutant MTC improved/remained stable on all domains of HRQoL during treatment with selpercatinib. Future analyses will be conducted as the data mature.

IMPLICATIONS FOR PRACTICE

Patients with metastatic medullary thyroid cancer (MTC) frequently experience disease-related diarrhea that can significantly impair daily living. Standards of care for the treatment of MTC include RET-targeted therapies as well as multikinase inhibitors (MKIs). Over 40% of patients with RET-mutant MTC who received selpercatinib, a highly selective RET inhibitor, reported clinical meaningful improvements in diarrhea in a phase I/2 study. Patient-reported diarrhea improved in 36.8% of patients who had no previous treatment with MKIs and in 51.3% of patients who had previous treatment with MKIs. The percentage of patients who reported diarrhea prior to selpercatinib initiation (80.4%) was reduced to less than half (range: 33.3%-48.3%) after Cycle 2 of selpercatinib treatment.