Lung cancer is the leading cause of cancer-related death worldwide, accounting for the highest mortality rates among both men and women. Most lung cancers—between 80% and 85%—are non–small cell lung cancer (NSCLC), and between 1% and 2% of patients are diagnosed with RET-altered NSCLC.
The results from a subgroup analysis of the LIBRETTO-431 trial investigating the efficacy and safety of the selective RET inhibitor selpercatinib in East Asian patients diagnosed with RET fusion–positive NSCLC showed that the treatment demonstrated improved progression-free survival compared with chemotherapy plus pembrolizumab. The agent was also deemed to be safe. These data support early comprehensive genomic testing and the use of selpercatinib as the preferred regimen in RET fusion–positive NSCLC across subpopulations of patients, according to the study authors. The study by Cheng et al is being presented during the 2024 ASCO Breakthrough meeting in Yokohama, Japan (Abstract 214).
Study Methodology
The LIBRETTO-431 trial is a randomized, open-label phase III study comparing first-line selpercatinib vs platinum-based pemetrexed with or without pembrolizumab. In prior studies, the efficacy and safety of selpercatinib were consistent in patients with RET fusion–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.
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 compared with Europe and the United States; incidence and mortality rates are 34.4 and 28.1 per 100,000, respectively.
Key Results
The researchers randomly assigned 142 patients from East Asia, and 116 were included in the analysis. A total of 75 patients received selpercatinib, and 41 received chemotherapy with or without pembrolizumab. Baseline patient 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 control group, the median progression-free survival was not yet reached in the selpercatinib group (95% confidence interval [CI] = 16.4 months to not reached) and was 11.1 months in the control group (95% CI = 7.0–16.8 months).
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.
Similar results were observed in patients from East Asia in the overall investigator’s intent-to-treat with pembrolizumab arm.
The most common adverse events reported in patients receiving selpercatinib included elevated aspartate aminotransferase (AST; 73.6%), elevated alanine aminotransferase (ALT; 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
“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: For full disclosures of the study authors, visit coi.asco.org.
