At the recently held 2024 Precision Medicine Conference on Lung Cancer, Dr. Nan Bi from the Cancer Hospital Chinese Academy of Medical Sciences, delivered a presentation titled "Advances in Radiotherapy for NSCLC in 2024." The talk covered key developments in radiotherapy combined with targeted therapy, radiotherapy combined with immunotherapy, and technological advancements in radiotherapy. In an exclusive interview with Oncology Frontier, Professor Bi further elaborated on some of the most pressing topics in this evolving field.

Key Advances in Radiotherapy-Immunotherapy Combinations for NSCLC in 2024

What are the latest developments in radiotherapy combined with immunotherapy for NSCLC without driver mutations?

Dr. Nan Bi: In 2024, significant progress was made in integrating radiotherapy with targeted and immunotherapy across early, mid, and late-stage NSCLC. Several landmark studies were published in major international journals, leading to guideline updates. However, some highly anticipated phase III trials reported negative results, indicating that certain approaches may not be viable.

For early-stage inoperable NSCLC, stereotactic body radiotherapy (SBRT) has long been the standard of care, offering excellent treatment outcomes. The question remains: Can adding immunotherapy further enhance efficacy? The I-SABR study published in 2023 suggested potential benefits, but the KEYNOTE-867 trial, a randomized, double-blind, placebo-controlled phase III study released in 2024, painted a different picture. It showed that SBRT plus pembrolizumab did not improve event-free survival (EFS) and significantly increased treatment-related adverse effects. These findings cast a shadow over the SBRT-immunotherapy approach, emphasizing the need to identify patient subgroups that could genuinely benefit from this combination, aligning with the principles of precision medicine.

In neoadjuvant therapy for NSCLC, the SACTION01 trial, conducted by Sun Yat-sen University Cancer Center, was the first global study to explore SBRT followed by sequential immunotherapy and chemotherapy for resectable stage IIA-IIIB NSCLC. The results were highly encouraging, showing a major pathologic response (MPR) rate of 76.1% and a pathologic complete response (pCR) rate of 52.2%, with good tolerability and feasibility. This study introduces a new perspective on neoadjuvant strategies, and a phase III randomized controlled trial is set to launch soon to validate these findings.

For unresectable stage III NSCLC, radiotherapy combined with immunotherapy remains a key focus. Historically, concurrent chemoradiotherapy (cCRT) has been the standard treatment for stage III unresectable NSCLC. This changed in 2017 when the PACIFIC trial demonstrated that 12 months of durvalumab consolidation therapy post-cCRT became the new standard of care. However, many patients experience disease progression during or shortly after chemoradiotherapy, preventing them from receiving consolidation therapy.

A major question in 2024 was whether immunotherapy could be initiated earlier, during concurrent chemoradiotherapy, rather than after it. However, two large phase III trials, PACIFIC-2 and CheckMate 73L, reported negative results, showing that adding immunotherapy upfront during cCRT did not improve outcomes. These findings suggest that this treatment approach is not viable. Future research will need to refine target area design, improve toxicity management, and explore new combination treatment strategies for locally advanced NSCLC.

For stage IV oligometastatic NSCLC, prior to the immunotherapy era, adding local treatment (such as radiotherapy or surgery) to chemotherapy or targeted therapy was shown to improve survival. Given this background, the NRG-LU002 trial, a phase II/III study, aimed to evaluate the benefit of local therapy after first-line immunochemotherapy. However, results presented at ASCO 2024 were disappointing. In patients with ≤3 extracranial metastatic lesions who had received at least four cycles of first-line systemic therapy without disease progression, adding local therapy (radiotherapy and/or surgery) failed to improve both progression-free survival (PFS) and overall survival (OS).

These findings suggest that a more refined risk stratification approach is needed for oligometastatic patients. Future research should focus on identifying patient subgroups that could benefit from radiotherapy-immunotherapy combinations and determining the optimal timing for incorporating local consolidative treatment into the treatment sequence.

Key Advances in Radiotherapy-Targeted Therapy Combinations for EGFR-Mutant NSCLC in 2024

What are the latest developments in combining radiotherapy with targeted therapy for EGFR-mutant NSCLC?

Dr. Nan Bi: In 2024, multiple studies reported significant benefits of consolidative TKI therapy following chemoradiotherapy (CRT) for patients with locally advanced EGFR-mutant NSCLC. This has led to a new standard of care where targeted therapy is integrated after CRT for unresectable stage III NSCLC with EGFR mutations.

A major breakthrough came from the LAURA study, presented at ASCO 2024, which for the first time confirmed that patients with EGFR-mutant, unresectable stage III NSCLC who remained progression-free after definitive CRT could achieve a dramatic improvement in median progression-free survival (PFS) with third-generation EGFR-TKI osimertinib (39.1 months vs. 5.6 months, HR=0.16), with acceptable toxicity levels. This landmark study has filled a critical gap in the precision treatment of NSCLC and has led to updates in treatment guidelines.

Previously, the ADAURA trial established the role of adjuvant EGFR-targeted therapy in early- and mid-stage NSCLC after surgery, while multiple trials in advanced disease had already confirmed the efficacy of targeted therapies. The LAURA trial now provides the first high-level evidence supporting targeted therapy for locally advanced NSCLC. Following this, the POLESTAR study, presented at WCLC 2024, reported similar findings, demonstrating a median PFS of 30.4 months with consolidative third-generation EGFR-TKI aumolertinib in patients who remained progression-free after definitive CRT.

Exploring the Synergy of Radiotherapy and Targeted Therapy

With targeted therapies effectively controlling systemic disease, an important question arises: Can adding radiotherapy further enhance outcomes?

The REFRACT study, the largest cohort study to date (N=440) for EGFR-mutant, unresectable stage III NSCLC, examined different treatment approaches and long-term survival outcomes. It found that patients who received TKI plus radiotherapy had significantly better PFS and overall survival (OS) compared to those who underwent CRT alone.

Additionally, the ADVANCE trial, a randomized controlled study, enrolled patients with EGFR-mutant, unresectable, non-squamous stage III NSCLC, comparing induction aumolertinib plus concurrent radiotherapy followed by aumolertinib consolidation against standard CRT. Preliminary data from ESMO 2024 already indicate a significant PFS benefit, with final results eagerly awaited.

Expanding the Role of Radiotherapy in Stage IV NSCLC

For stage IV NSCLC, several studies in 2024 explored the potential of TKI combined with thoracic radiotherapy (TRT) to improve survival outcomes.

The NROG-002 trial investigated whether EGFR-TKI (icotinib) combined with TRT could offer additional benefits over EGFR-TKI monotherapy in EGFR-mutant oligometastatic NSCLC. The results demonstrated that early addition of TRT to TKI therapy significantly improved local control and long-term survival, even for patients with ≥5 metastatic lesions, challenging the traditional definition of “oligometastatic disease.”

These findings suggest that selective integration of local radiotherapy in stage IV NSCLC could be a viable treatment strategy, warranting further investigation into optimal patient selection and treatment sequencing.

Dr. Nan Bi

Cancer Hospital Chinese Academy of Medical Sciences

• MD, PhD, Chief Physician, Doctoral Supervisor
• Postdoctoral Visiting Scholar, University of Michigan, USA
• Deputy Director of the Department of Radiation Oncology, Head of the Thoracic Radiation Group
• Vice Chair of the Youth Committee, Chinese Medical Association Radiation Oncology Branch
• Vice Chair of the Youth Committee, Radiation Oncology Section, Chinese Anti-Cancer Association
• Board Member of CSCO, Committee Member of NSCLC, SCLC, and Radiation Oncology Sections
• Lead Author of the Small Cell Lung Cancer Guidelines
• Editorial Board Member of Chinese Journal of Radiation Oncology
• Deputy Editor-in-Chief of Tumor Clinical and Rehabilitation
• Recipient of the IASLC ‘Developing Nation Award’
• National Science and Technology Progress Award (Second Prize)
• Two Provincial/Ministerial Science and Technology Progress Awards (Second Prize)
• Beijing Outstanding Physician Award
• First or corresponding author of publications in Lancet Oncology, Annals of Oncology, Molecular Cancer, Clinical Cancer Research, Cancer Research, JAMA Network Open, and others
• Research findings cited in ASCO, ASTRO, ESMO, and CSCO guidelines
• Included in ASTRO Continuing Medical Education (CME) programs