Selpercatinib shows durable response in RET-fusion positive NSCLC
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Among patients with RET-fusion positive non-small cell lung cancer, selpercatinib was well tolerated and demonstrated marked and durable anti-tumor response, according to findings from the LIBRETTO-001 trial presented at the virtual ASCO20 Annual Meeting.
“LOXO-292, or selpercatinib, is a highly potent selective RET-inhibitor,” Vivek Subbiah, MD, associate professor at The University of Texas MD Anderson Cancer Center, told Healio.
For the ongoing phase 1/2 global, multicenter trial, the researchers enrolled patients with RET-fusion positive non-small cell lung cancer, in addition to other RET-altered cancers. The first phase of the trial was focused on dose escalation and patients in the second phase received selpercatinib (Retevmo; Eli Lilly) at the recommended dose of 160 mg orally twice daily for a 28-day cycle.
The primary endpoint was objective response rate (ORR) as assessed by an independent review committee (IRC), while the secondary endpoints were duration of response and safety. The primary analysis set comprised the first 105 consecutively enrolled patients across both phases of the study who had previously been treated with platinum-based chemotherapy. Patients with treatment-naïve non-small cell lung cancer were analyzed separately.
The IRC reported an ORR of 64% (95% CI; 54–73) among heavily pretreated patients who received prior platinum-based chemotherapy, and the response did not differ by fusion partner or number or type of prior therapies. The median duration of response was 18 (95% CI; 12–NE) months, with 66% of patients in ongoing response and censored.
The study included 39 treatment-naive patients with an ORR of 85% (95% CI; 70–94), according to the IRC. At the median duration of follow-up of 7 months, 79% of confirmed responses were ongoing and censored and median duration of response had not been reached, the researchers reported.
The safety analysis included 531 patients who received selpercatinib as of June 17, 2019. The most common treatment-related adverse events were dry mouth, increased AST, increased ALT, hypertension, diarrhea, fatigue and peripheral edema, and only 2% of patients discontinued treatment due to treatment-related adverse events.
The data demonstrated the tolerability of selpercatinib as well as its marked and durable antitumor activity among patients with RET-fusion positive non-small cell lung cancer.
“These impressive results not only led to the approval of selpercatinib as the first-in-class selective RET inhibitor for the treatment of patients with metastatic RET fusion-positive non-small cell lung cancer, but they also underscore the importance of broad-based genomic profiling to appropriately characterize patients with non-small cell lung cancer for targeted treatment decisions,” Subbiah said.
“As a follow up to this important milestone, a better understanding of acquired resistance mechanisms to selective RET inhibitors and the ensuing strategies aimed at abrogating them should be prioritized to further advance the science in RET-altered non-small cell lung and thyroid cancers.”
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Goto K, et al. Abstract 3584. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
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