Selpercatinib in RET Fusion–Positive Solid Tumors Other Than Lung or Thyroid Malignancies

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As reported in The Lancet Oncology by Vivek Subbiah, MD, and colleagues, the phase I/II LIBRETTO-001 basket trial has shown that the RET kinase inhibitor selpercatinib demonstrated activity in patients with RET fusion–positive solid tumors in an analysis excluding lung and thyroid cancers. Findings from the study supported the May 2020 accelerated approval of selpercatinib in advanced RET-driven lung and thyroid cancers, as well as this week’s regular approval in locally advanced or metastatic RET fusion–positive non–small cell lung cancer and accelerated approval in RET fusion–positive solid tumors.

Vivek Subbiah, MD

Vivek Subbiah, MD

Study Details

Forty-five patients from sites in eight countries were enrolled between December 2017 and August 2021; the trial is still ongoing. Eligible patients had disease progression on or after previous systemic therapies or no satisfactory therapeutic options.

Patients received selpercatinib in continuous 28-day cycles at 20 mg once daily or at 20 to 240 mg twice daily in the dose-escalation phase, or at the phase II recommended dose of 160 mg twice daily. A total of 91% of patients had received at least one prior line of systemic therapy (median = 2); 96% had a history of metastatic disease. The most common diagnoses were gastrointestinal malignancies (n = 26, 58%).

The primary endpoint was objective response rate determined by independent review committee. The efficacy-evaluable population was defined as patients who had at least 6 months of follow-up from the first study dose at the time of data cutoff; all responders at the time of data cutoff were followed up for at least 6 months from the onset of response (unless they experienced disease progression or death).


In total, 44 of 45 patients received selpercatinib at 160 mg twice daily (1 at 120 mg twice daily). Among 41 efficacy-evaluable patients, an objective response was observed in 18 (43.9%, 95% confidence interval [CI] = 28.5%–60.3%), with a complete response seen in 2 (5%). Clinical benefit was achieved in 26 patients (63.4%, 95% CI = 46.9%–77.9%). The median duration of response was 24.5 months (95% CI = 9.2 months–not evaluable).

Responses were observed in all eight histologies in which at least two patients were enrolled and in four of seven that had one patient enrolled. Among the most common cancers, responses were observed in 6 of 11 patients with pancreatic cancer, 2 of 10 with colon cancer, and 2 of 4 with salivary cancer.

Median progression-free survival was 13.2 months (95% CI = 7.4–26.2 months), with an estimated 1-year rate of 53.1%. Median overall survival was 18.0 months (95% CI = 10.7 months–not evaluable), with an estimated 18-month rate of 51.7%.


  • Objective response was observed in 44% of patients.
  • Median duration of response was 24.5 months.

Adverse Events

Among all 45 patients, grade ≥ 3 adverse events occurred in 56%, most commonly hypertension (22%), increased alanine aminotransferase (16%), and increased aspartate aminotransferase (13%). Serious adverse events occurred in 40% of patients, most commonly abdominal pain, nausea, pyrexia, and vomiting (in 4% each). Adverse events led to death in three patients (due to dyspnea, aspiration, and neoplasm progression, respectively); none of the deaths was considered related to treatment.

The investigators concluded, “Selpercatinib showed clinically meaningful activity in the RET fusion–positive tumor-agnostic population, with a safety profile consistent with that observed in other indications. Comprehensive genomic testing that includes RET fusions will be crucial for identifying patients who might benefit from selpercatinib.”

Dr. Subbiah, of the Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Loxo Oncology. For full disclosures of the study authors, visit

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