ADVANCE Phase III Study Results Published

Background

Locally advanced, or stage III, non-small cell lung cancer (NSCLC) that is unresectable and harbors EGFR mutations (exon 19 deletion or L858R) has historically been treated with concurrent chemoradiotherapy. This approach combines platinum-based chemotherapy with radiation but is associated with notable toxicity. Subgroup analyses from prior trials had indicated that certain consolidative immunotherapies may provide limited benefit in EGFR-mutated cases.

The ADVANCE phase III trial (ChiCTR2000040590) was designed as the first randomized study to evaluate a chemotherapy-free strategy in this specific population. Led by Professor Nan Bi of the Cancer Hospital, Chinese Academy of Medical Sciences, along with collaborators including Wang Lvhua, the multicenter, open-label trial compared aumolertinib combined with radiotherapy against standard concurrent chemoradiotherapy. The results were published in Signal Transduction and Targeted Therapy in September 2026.

What was achieved

The trial enrolled 43 eligible patients (24 in the experimental arm and 19 in the control arm) instead of the planned 98 and was terminated early after a pre-specified interim analysis due to a large observed difference in outcomes, slow accrual, and loss of equipoise in an open-label setting. At a median follow-up of 25.5 months, the experimental arm demonstrated a median progression-free survival (PFS) of 34.0 months compared with 7.4 months in the chemoradiotherapy arm (hazard ratio 0.15; 95% CI 0.06-0.38; P<0.001). This corresponds to an 85% reduction in the risk of disease progression or death.

The 12-month PFS rates were 79.2% versus 44.7%, and the 24-month PFS rates were 59.4% versus 0%. Median overall survival was not reached in the experimental arm versus 30.5 months in the control arm (HR 0.32; P=0.09). In a subgroup resembling populations in related studies, further PFS and OS benefits were noted. Safety favored the experimental arm, with lower rates of neutropenia (16.7% vs 52.6%) and nausea (0% vs 26.3%), no grade 4-5 adverse events reported in the experimental group, and better quality-of-life scores. These findings were supported by real-world data from a cohort of 125 patients showing superior outcomes with TKI plus radiotherapy approaches compared with chemoradiotherapy alone.

How it works

EGFR mutations cause the epidermal growth factor receptor protein on cancer cells to send continuous growth signals, leading to uncontrolled proliferation. Aumolertinib is a third-generation EGFR tyrosine kinase inhibitor that specifically binds to and blocks these mutated receptors inside the cell. This inhibits downstream signaling pathways, slowing or stopping cancer cell growth and promoting cell death while sparing normal cells to a greater degree than earlier generations of drugs.

Radical radiotherapy delivers precisely targeted high-energy radiation beams to the primary tumor in the lung and involved lymph nodes, typically totaling around 60 Gy over several weeks. The radiation damages the DNA of cancer cells, preventing them from dividing and causing them to die. In the ADVANCE regimen, aumolertinib was given daily as induction therapy for nine weeks to reduce tumor burden, then continued concurrently with radiotherapy, and followed by maintenance until progression. This targeted and radiation combination aims to control both local and distant disease without the addition of traditional cytotoxic chemotherapy agents such as cisplatin and pemetrexed.

What it means for international patients

The ADVANCE results indicate that a chemotherapy-free combination of aumolertinib and radical radiotherapy can substantially extend progression-free survival and improve tolerability compared with standard chemoradiotherapy for patients with unresectable stage III EGFR-mutant NSCLC. International patients with this molecular profile and disease stage may wish to discuss such targeted radiotherapy approaches with specialists. However, individual eligibility depends on factors including exact mutation type, performance status, organ function, and full staging assessment.

The Cancer Hospital, Chinese Academy of Medical Sciences maintains special medical services that support international and overseas patients, including pathways for consultation and treatment of complex cancers such as lung cancer. Patients should contact the hospital directly to confirm current availability, eligibility criteria for this or similar regimens, and any requirements for medical records review or in-person evaluation. Treatment decisions must be made in consultation with qualified physicians based on the latest clinical data and individual circumstances.

About the hospital

The Cancer Hospital, Chinese Academy of Medical Sciences is located in Beijing. Founded in 1958, it was the first specialized cancer hospital established in the People's Republic of China and remains one of the largest. It is affiliated with the Chinese Academy of Medical Sciences and Peking Union Medical College and was designated as the National Cancer Center.

It operates as a Grade A tertiary specialist hospital with approximately 1,500 beds. The hospital handles high annual volumes of cancer care, including outpatient visits exceeding one million, tens of thousands of inpatient admissions, and thousands of operations. It consistently ranks first among tertiary oncology hospitals in national performance evaluations and maintains strengths in radiation oncology, thoracic tumor treatment, multidisciplinary care, and clinical research. It houses national key laboratories and serves as a base for cancer prevention, treatment, and drug clinical trials. The hospital provides services for international patients through its special medical department.