ASCO Breakthrough 2024: Key Advances in the NSCLC Landscape with First-line Treatment Selpercatinib Trial Updates

The ASCO Breakthrough 2024, held in Japan from August 8-10, showcases the latest advancements in oncology. This meeting highlights cutting-edge treatments and research focus areas, presenting several abstracts on various cancers. A new subgroup analysis from the Phase 3 LIBRETTO-431 trial demonstrates that selpercatinib, a selective RET inhibitor, significantly enhances progression-free survival in East Asian patients with RET fusion-positive non-small cell lung cancer (NSCLC). This analysis confirms selpercatinib’s effectiveness and safety for this demographic, aligns with findings from the broader population, and reinforces its role as a preferred first-line treatment for RET fusion-positive NSCLC.

Selpercatinib Enhances Progression-Free Survival in East Asian Patients with RET Fusion-Positive NSCLC

Lung cancer ranks as the second most commonly diagnosed cancer and leads globally in cancer deaths. Approximately 85% of individuals diagnosed with lung cancer will have NSCLC. Among those with NSCLC, about 1% to 2% will exhibit changes to the RET gene known as RET fusion.

The Phase 3 LIBRETTO-431 study (NCT04194944) evaluated the effectiveness of selpercatinib, a selective RET inhibitor, in treating RET fusion-positive NSCLC compared to platinum-based chemotherapy with or without pembrolizumab. Researchers recently analyzed the data from this trial, focusing on patients from East Asia, including China, Hong Kong, Japan, the Republic of Korea, and Taiwan. Asia has the highest incidence of lung cancer, and as such the aim of the investigation was to confirm whether selpercatinib is also effective in this specific population. 

An RET inhibitor is a type of targeted therapy designed to block the activity of the RET (rearranged during transfection) protein, which is involved in certain cancers. The RET protein is a receptor tyrosine kinase that, when mutated or abnormally activated, can drive the growth of cancer cells. By inhibiting this protein, RET inhibitors aim to slow or stop the growth of tumors that depend on RET signaling for their progression. These inhibitors are particularly useful in treating cancers with RET gene fusions or mutations, such as certain types of NSCLC and medullary thyroid cancer. 

Selpercatinib vs. Chemotherapy: Superior 12-Month PFS and Response Rate in East Asian NSCLC Patients

In the analysis of 116 East Asian patients, 75 received selpercatinib while 41 were treated with chemotherapy, with or without pembrolizumab. After a median follow-up of 19.4 months for the selpercatinib group and 21.2 months for the control group, the selpercatinib group had not yet reached a median progression-free survival (PFS), whereas the control group had a median PFS of 11.1 months. Furthermore, at the 12-month mark, 72.8% of patients in the selpercatinib group had cancer that had not progressed, compared to 41.7% in the control group. Additionally, the overall response rate for selpercatinib was 86.7%, in contrast to 61% for the control group.

Dr. David R. Spigel, Chief Scientific Officer at Sarah Cannon Research Institute, commented, “We cannot always assume that effective therapies in a general population will maintain the same level of efficacy and safety in specific subpopulations. These outstanding results provide confidence that selpercatinib is both effective and safe for East Asian patients with newly diagnosed RET-altered NSCLC.”

Key Advances in the NSCLC Landscape: Ivonescimab Outperforms KEYTRUDA in Recent Phase 3 Trial

The treatment landscape for resectable early-stage NSCLC is undergoing significant changes due to promising results from randomized trials on neoadjuvant and adjuvant immunotherapy, as well as adjuvant targeted therapy. Consequently, for advanced-stage NSCLC, the number of EMA-approved targeted therapies for metastatic lung cancer has surged over the past two decades and is expected to expand rapidly in the future.

In this evolving arena, ivonescimab, a bispecific antibody developed by Summit Therapeutics and Akeso, is a significant market option to pay attention to. Just one week after receiving approval from Chinese regulators, ivonescimab demonstrated its competitive edge by surpassing KEYTRUDA, a leading PD-1 inhibitor, in the Phase 3 HARMONi-2 trial. Conducted exclusively in China, this trial revealed that ivonescimab significantly improved progression-free survival (PFS) compared to KEYTRUDA monotherapy, thus meeting its primary endpoint. This advancement highlights ivonescimab’s potential as a strong contender in treating non-small cell lung cancer (NSCLC), particularly among patients with PD-L1-expressing tumors.

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Author

Bernice Lottering