Selpercatinib (Retevmo) demonstrated antitumor activity in RET fusion–positive tumors other than lung cancer and thyroid cancer, according to interim results from the phase 1/2 LIBRETTO-001 clinical trial. These findings were presented by Vivek Subbiah, MD, Medical Director, Clinical Center for Targeted Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, at the 2021 virtual American Association for Cancer Research annual meeting.
“RET fusions in tumors other than lung or thyroid are uncommon but potentially actionable. Selpercatinib demonstrates promising activity across a variety of advanced solid tumors, including multiple treatment-refractory gastrointestinal malignancies. Efficacy was observed across cancer types and a spectrum of fusion partners. Selpercatinib was well-tolerated with no new safety signals,” Dr Subbiah reported. “These results underscore the importance of broad-based genomic profiling. It is essential to identify oncogenic drivers, including RET fusions,” he added.
Selpercatinib, a first-in-class, highly selective, small-molecule RET-related kinase inhibitor, is currently approved by the FDA for the treatment of 2 RET fusion−positive tumor types—metastatic non−small-cell lung cancer (NSCLC) and thyroid cancer. The FDA granted accelerated approval for these indications based on results from the LIBRETTO-001 trial.
LIBRETTO-001 was a multicenter phase 1/2 trial that evaluated the safety and efficacy of selpercatinib in patients with advanced metastatic RET fusion–positive solid tumors. Total enrollment in the study was 441 patients with RET fusion–positive cancers. Most patients (80.7%) had NSCLC, followed by thyroid cancer (10.7%), and other cancers (8.6%). Selpercatinib was administered orally in 28-day cycles until disease progression, death, unacceptable adverse events, or patient withdrawal. Patients who were enrolled in the phase 1 dose-escalation portion of the study received selpercatinib ranging from 20 mg once daily to 240 mg twice daily. All patients enrolled in the phase 2 portion of the study received the recommended dose of 160 mg twice daily.
Dr Subbiah presented data on the 38 patients who had cancer other than NSCLC or thyroid cancer, including those with pancreatic, colon, breast, salivary, sarcoma, carcinoid, rectal neuroendocrine, small intestine, ovarian, pulmonary carcinosarcoma, and unknown primary cancers. Among the 32 patients evaluable for efficacy, 62.5% had gastrointestinal tumors (defined as pancreatic [N = 9], colon [N = 9], small intestine [N = 1], and rectal neuroendocrine [N = 1]). The overall response rate was 47%, including 2 complete responses and 13 partial responses. Three patients with response in nontarget lesions were not included in the response analysis. Approximately 73% of patients were still on treatment at the time of the presentation.
Safety was consistent with the overall population in the trial, and adverse events were typically dose-dependent. The most common (>20%) treatment-emergent adverse events of any grade that occurred in the 38 patients evaluable for safety were dry mouth (38.9%), diarrhea (36.6%), hypertension (35.9%), fatigue (35.0%), edema (34.5%), and liver toxicities (aspartate aminotransferase increase, 29.9%; alanine transaminase increase, 28.6%). No patient discontinued treatment because of a treatment-related adverse event.
Ezra E.W. Cohen, MD, FRCPSC, FASCO, Associate Director, Translational Science, and Leader, Solid Tumor Therapeutics Research Program, Moores Cancer Center, University of California San Diego Health, an invited discussant, emphasized the importance of genetic profiling.
“The molecular profiling of patients must become universally available. It is no longer a question of if, but how, we do molecular profiling. We need health policy and guidelines for testing. Selective targeting yields fewer patients but greater efficacy with a targeted treatment. We need to develop proactive approaches,” he said.
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