RET fusion-positive lung cancer: a field transformed by science
RET fusion-positive non-small cell lung cancer (NSCLC) is a rare, molecularly defined subtype of lung cancer. For many years, people with this diagnosis had access to limited treatment options. That has changed significantly.
New data presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting show that targeted therapies are now available across multiple stages of RET fusion-positive NSCLC, with further options in development for people whose cancer has become resistant to existing treatments.
This page explains what RET fusion-positive lung cancer is, how it is diagnosed, what treatments are currently available, and what the latest science means for people living with this diagnosis.
What is a RET fusion?
RET is a gene that provides instructions for making a protein involved in normal cell growth and survival. In some lung cancers, the RET gene becomes abnormally joined to another gene. This joining is called a fusion. The resulting fusion protein is permanently switched on, sending continuous signals that drive cancer cell growth.
RET fusions are not caused by smoking. They occur as a random error in the way DNA is copied or repaired. People with RET fusion-positive lung cancer are more likely to be younger adults and never or light smokers, though anyone can develop this subtype.
The most common RET fusion partner gene is KIF5B, which accounts for approximately 65% of RET fusions in lung adenocarcinoma. The second most common is CCDC6. Research presented at ASCO 2026 suggests that the fusion partner may influence how the cancer behaves and how well it responds to certain treatments. This is an active area of investigation.
How common is RET fusion-positive lung cancer?
RET fusions are found in approximately 1 to 2% of all NSCLC cases. NSCLC accounts for around 85% of all lung cancer diagnoses. Across Europe, where nearly 400,000 people are diagnosed with lung cancer each year, this means several thousand people annually may have RET fusion-positive disease.
Because the proportion is small, RET fusion-positive lung cancer is classified as a rare molecular subtype. However, the number of people affected globally is significant, and the research community has invested substantially in developing treatments specifically for this group.
How is RET fusion-positive lung cancer diagnosed?
RET fusions are identified through biomarker testing, specifically through a technique called next-generation sequencing (NGS). NGS can analyse tumour tissue or, in some cases, a blood sample (liquid biopsy) to detect genetic alterations including RET fusions.
Comprehensive biomarker testing at diagnosis is essential for anyone with NSCLC. Without testing, a RET fusion will not be identified, and targeted treatment options may not be offered. Testing should ideally be performed before any treatment decision is made.
If you have been diagnosed with NSCLC and have not had comprehensive biomarker testing, ask your oncologist whether NGS testing is available and appropriate for your situation.
What treatments are available?
Targeted therapies for advanced or metastatic RET fusion-positive NSCLC
Two selective RET inhibitors are currently approved for the treatment of advanced or metastatic RET fusion-positive NSCLC.
Selpercatinib (Retevmo) was the first highly selective RET inhibitor to reach approval. It has demonstrated superior progression-free survival compared with chemotherapy combined with immunotherapy in previously untreated people with advanced RET fusion-positive NSCLC. Selpercatinib is taken orally as a capsule, twice daily. It has shown activity against brain metastases, which is clinically relevant because RET fusion-positive tumours can spread to the brain.
Pralsetinib (Gavreto) is a second selective RET inhibitor approved for metastatic RET fusion-positive NSCLC. Phase 3 data from the AcceleRET-Lung study, presented at ASCO 2026, showed that pralsetinib significantly improved progression-free survival compared with standard chemotherapy, with a median of 18.7 months versus 9.0 months. Response rates were also substantially higher with pralsetinib (65.5% versus 41.6%). An increased rate of infections was observed with pralsetinib in this study, and monitoring for infections is recommended.
Both drugs represent a significant advance over chemotherapy alone and are generally preferred as first-line treatment for people with advanced RET fusion-positive NSCLC when access is available.
Adjuvant therapy for early-stage RET fusion-positive NSCLC
Until 2026, no targeted therapy had been approved for use after surgery in people with early-stage RET fusion-positive NSCLC. This gap in care meant that people who had undergone surgery remained at significant risk of their cancer returning, with no targeted option to reduce that risk.
Results from the phase 3 LIBRETTO-432 trial, presented at the ASCO 2026 Plenary Session and published simultaneously in the New England Journal of Medicine, address this gap directly.
LIBRETTO-432 enrolled 151 people with stage IB to IIIA RET fusion-positive NSCLC across 22 countries. Participants had already completed surgery or radiotherapy. They were randomly assigned to receive either adjuvant selpercatinib or placebo for up to three years.
In people with stage II to IIIA disease, the primary analysis group, the two-year event-free survival rate was 91.5% with selpercatinib compared with 61.1% with placebo. This represents an 83% reduction in the risk of recurrence, progression, or death (hazard ratio 0.172). In the broader stage IB to IIIA population, two-year event-free survival was 93.8% with selpercatinib versus 69.6% with placebo.
Side effects with adjuvant selpercatinib were consistent with its known profile. The most common grade 3 or higher events were elevations in liver enzymes and high blood pressure. These were generally manageable with dose adjustments. No new safety signals were identified.
Experts at ASCO 2026 described these results as practice-changing, noting that targeted therapy has now demonstrated benefit across multiple stages of RET fusion-positive NSCLC, following earlier successes in EGFR-positive and ALK-positive disease.
Overall survival data from LIBRETTO-432 are not yet mature and longer follow-up will be needed.
Selpercatinib is already approved in Europe for advanced RET fusion-positive NSCLC. The adjuvant indication presented at ASCO 2026 is not yet authorised in Europe. Regulatory review will follow. Lung Cancer Europe will update this page as the process progresses.
What does the future look like?
Research at ASCO 2026 also highlighted several next-generation RET inhibitors in development, addressing a key challenge: what happens when a RET fusion-positive cancer stops responding to selpercatinib or pralsetinib.
Lunbotinib is a next-generation brain-penetrant RET inhibitor studied in a pivotal phase II trial in China, with a Western population trial ongoing. In people who had received prior chemotherapy and immunotherapy, the confirmed response rate was 87.1%. In treatment-naive people, it was 81.3%. Among those with brain metastases at baseline, response rates were 82.6% and 75.0% respectively, with complete intracranial responses observed in both groups.
Soxataltinib (SY-5007) demonstrated a confirmed response rate of 90.0% in a phase III confirmatory trial in previously untreated people with RET fusion-positive NSCLC. Median progression-free survival had not been reached at the time of analysis.
APS03118 is a next-generation RET inhibitor specifically designed to work in people whose cancer has become resistant to first-generation selective RET inhibitors such as selpercatinib or pralsetinib. Early phase I data show a 23% response rate in people with prior RET inhibitor failure and no known bypass resistance mutations, with promising signals in those with specific resistance mutations. An 80% response rate was observed in treatment-naive people.
These drugs are not yet approved and are available only through clinical trials. They represent the next wave of options being investigated for a population whose needs continue to be taken seriously by the research community.
Research is also exploring the role of fusion partners in predicting treatment response, the impact of co-occurring mutations such as TP53, and how biomarker testing can be used to guide treatment sequencing over time.
What should you do if you have RET fusion-positive lung cancer?
Ask about biomarker testing. If you have been diagnosed with NSCLC and have not had comprehensive genomic profiling, ask your oncologist whether NGS testing is available. Knowing your molecular subtype is the foundation of access to targeted treatment.
Ask about your fusion partner. If your test results show a RET fusion, ask which gene your RET has fused with. Research suggests this detail may become increasingly relevant to treatment decisions.
Ask about clinical trials. Next-generation RET inhibitors are being studied in clinical trials globally. If you have received prior treatment and are looking for further options, ask your oncologist whether any trials are open to you.
Connect with others. Living with a rare molecular subtype of lung cancer can feel isolating. Lung Cancer Europe connects people across Europe living with lung cancer and their families. Our member organisations and community can provide support, information, and connection.
Read more:
Europe’s Medicine Access Crisis: What the Latest Data Means for Lung Cancer
The EU Biotech Act: what it means for people living with lung cancer
Lung cancer in women: what ASCO 2026 and a new Nature review tell us
Blood test predicts lung cancer five years early: what the new Cell research means
Lung Cancer Europe is at ASCO for the first time. Here is why.
About this page
This page is produced by Lung Cancer Europe and reflects published scientific data and abstracts presented at the 2026 ASCO Annual Meeting. It is not a substitute for personalised medical advice. Treatment availability varies across Europe. Please speak with your oncologist about the options relevant to your situation.
Key sources: LIBRETTO-432 trial (Goldman et al., NEJM 2026); AcceleRET-Lung (Popat et al., ASCO 2026 abstract 8504); Lunbotinib phase II (Zhou et al., ASCO 2026 abstract 8505); Soxataltinib phase III (Xiong et al., ASCO 2026 abstract 8639); APS03118 phase I (Lu et al., ASCO 2026 abstract 8617); RET fusion partner characteristics (Sun et al., ASCO 2026 abstract 8615).