A subgroup analysis of data from the LIBRETTO-431 trial (ClinicalTrials.gov identifier NCT04194944) showed that the selective RET inhibitor selpercatinib safely improved progression-free survival compared to chemotherapy plus pembrolizumab in East Asian patients diagnosed with RET fusion–positive non–small cell lung cancer (NSCLC). These data support early comprehensive genomic testing and the use of selpercatinib as the preferred regimen in RET-positive NSCLC across subpopulations of patients.1 The study by Ying Cheng, MD, of the Jilin Provincial Cancer Hospital in Jilin Province, China, and colleagues was presented during the 2024 ASCO Breakthrough meeting in Yokohama, Japan.
Ying Cheng, MD
Lung cancer is the leading cause of cancer-related death worldwide, accounting for the highest mortality rates among both men and women.2 Between 80% and 85% of lung cancers are NSCLC, and between 1% and 2% of patients are diagnosed with RET-altered NSCLC. 3,4
Study Methodology
The LIBRETTO-431 trial is a randomized, open-label phase III study comparing first-line selpercatinib vs standard treatment with platinum-based pemetrexed with or without pembrolizumab. In prior studies, the efficacy and safety of selpercatinib were consistent in RET-positive NSCLC across geographies. As previously reported, LIBRETTO-431 met its primary endpoint of improved progression-free survival by blinded independent central review at the preplanned interim analysis.
The researchers conducted a new analysis of the data collected during this trial comparing selpercatinib and the control treatment in patients from several countries in East Asia, including China, Hong Kong, Japan, Republic of Korea, and Taiwan, to assess whether the drug is also effective in this specific patient population. The incidence and mortality of lung cancer are higher in Asia—34.4 and 28.1 per 100,000, respectively—compared with Europe and the United States.5
Results
The researchers randomly assigned 142 patients from East Asia; 116 were included in the analysis. Seventy-five patients received selpercatinib, and 41 received chemotherapy with or without pembrolizumab. Baseline characteristics were well balanced between the two groups; however, the selpercatinib arm had slightly more patients from East Asia vs the control arm (58% vs 49%).
After a median follow-up of 19.4 months in the selpercatinib group and 21.2 months in the chemotherapy group, the median progression-free survival was not yet reached among selpercatinib-treated patients (95% confidence interval [CI] = 16.4 months to not estimable) vs 11.1 months among those in the control group (95% CI = 7.0–16.8 months).
KEY POINTS
- The selective RET inhibitor selpercatinib demonstrated superior improved progression-free survival in East Asia patients diagnosed with RET fusion–positive non–small lung cancer compared to chemotherapy plus pembrolizumab.
- The findings support early comprehensive genomic testing and the use of selpercatinib as the preferred regimen in RET fusion–positive NSCLC across subpopulations of patients.
After 12 months, the percentage of patients whose cancer had not progressed was 72.8% in the selpercatinib group and 41.7% in the control group. The overall response rate was 86.7% (95% CI = 76.8%–93.4%) in the selpercatinib arm vs 61.0% (95% CI = 44.5%–75.8%) in the control arm.
The most common adverse events reported in patients in the selpercatinib arm included elevated aspartate aminotransferase (AST) levels (73.6%), elevated alanine aminotransferase (ALT) levels (70.3%), hypertension (60.4%), increased blood bilirubin (52.7%), and diarrhea (44.0%). The most common adverse events in the control group included anemia (61.2%), elevated AST levels (49.0%), leukopenia (49.0%), neutropenia (44.9%), and elevated ALT levels (42.9%).
“LIBRETTO-431 is the first randomized study to report efficacy and safety of a RET inhibitor in patients from East Asia. Consistent with the results in the overall population, selpercatinib demonstrated superior progression-free survival compared to chemotherapy plus pembrolizumab in first-line patients from East Asia. These data support early comprehensive genomic testing and the use of selpercatinib as the preferred first-line regimen in [RET fusion–positive] NSCLC patients across geographies,” concluded the study authors.
Clinical Significance
David R. Spigel, MD
“We cannot always assume that effective therapies in a general population will still be effective and safe in subpopulations,” commented David R. Spigel, MD, Chief Scientific Officer at the Sarah Cannon Research Institute, in a statement about the study’s findings. “These outstanding results provide confidence that selpercatinib is an effective and safe treatment for East Asian patients with newly diagnosed RET-altered NSCLC.”
DISCLOSURE: Dr. Cheng reported no conflicts of interest. For full disclosures of his coauthors, visit https://coi.asco.org/Report/ViewAbstractCOI?id=467924.
REFERENCES
1. Cheng Y, Loong HH, Zhou C, et al: Efficacy and safety of 1L selpercatinib in RET fusion-positive NSCLC: LIBRETTO-431 East Asian subgroup analysis. 2024 ASCO Breakthrough. Abstract 214. Presented August 8, 2024.
2. World Health Organization: Lung Cancer: Key Facts. Available at www.who.int/news-room/fact-sheets/detail/lung-cancer. Accessed August 8, 2024.
3. American Cancer Society: Key Statistics for Lung Cancer. Available at www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html. Accessed August 8, 2024.
4. Shen Z, Qiu B, Li L, et al: Targeted therapy for RET fusion-positive non-small cell lung cancer. Front Oncol 12:1033484, 2022.
5. Lam DCL, Liam C-K, Andarini S, et al: Lung cancer screening in Asia: An expert consensus report. J Thorac Oncol 18:1303-1322, 2023.
