A phase II clinical study on the sequential use of Adebrelimab combined with chemotherapy followed by thoracic radiotherapy has garnered widespread attention at ASCO 2024, particularly for its impact on the treatment of extensive-stage small cell lung cancer (ES-SCLC).The results are striking: the regimen significantly prolonged progression-free survival (PFS) and overall survival (OS) compared to existing standards, while maintaining a favorable safety profile. Most notably, this strategy set a new survival benchmark for first-line immunotherapy in SCLC, demonstrating the value of integrating immune checkpoint inhibition with thoracic radiotherapy. This innovative approach represents a major step forward in SCLC treatment and offers renewed hope for patients battling this aggressive disease. In light of these findings, Oncology Frontier invited Academician Jinming Yu to share insights into the study design, key outcomes, and its clinical implications. The following is a summary of his expert commentary.

Oncology Frontier: At ASCO Annual Meeting, your hospital’s phase II study on first-line treatment of ES-SCLC using Adebrelimab combined with chemotherapy followed by thoracic radiotherapy was selected for oral presentation. Could you share the background and rationale behind this study?

Academician Jinming Yu: The rapid development of immunotherapy has brought new hope for patients with extensive-stage small cell lung cancer (ES-SCLC). The combination of chemotherapy and immunotherapy has now become the standard first-line treatment for ES-SCLC.

The IMpower133 trial was the first to demonstrate that combining a PD-L1 inhibitor with chemotherapy could significantly improve survival in ES-SCLC, with median overall survival surpassing the one-year mark for the first time. The CASPIAN trial later confirmed the efficacy of PD-L1 inhibitors in this setting. However, it’s worth noting that both studies included only a small proportion of Asian patients.

The approval of Adebrelimab, the first domestically developed PD-L1 inhibitor in China, has been a major milestone. In Chinese patients with ES-SCLC, it pushed the median overall survival (mOS) beyond 15 months. The phase III CAPSTONE-1 trial, published in The Lancet Oncology, was the first to confirm the remarkable efficacy of PD-L1 inhibitors specifically in the Chinese ES-SCLC population.

While the combination of immunotherapy and chemotherapy has opened the door to long-term survival, the question remains: how can we further improve outcomes and expand the group of patients who benefit from immunotherapy? Radiotherapy and immunotherapy have shown synergistic effects at the mechanistic level. This led us to explore whether adding thoracic radiotherapy to standard immuno-chemotherapy could further enhance clinical efficacy.

Before launching this phase II clinical trial, our center identified a novel senescence-related molecular subtype of SCLC. We discovered that this subtype, under radiotherapy, increases PD-L1 expression and modulates the tumor immune microenvironment. This preclinical insight provided a strong rationale for conducting the current study, which aims to evaluate the efficacy and safety of sequential thoracic radiotherapy following Adebrelimab and chemotherapy in ES-SCLC patients.

Oncology Frontier: Could you highlight the key features and findings of this study?

Academician Jinming Yu: This study represents the first prospective phase II trial in China to investigate Adebrelimab combined with chemotherapy followed by thoracic radiotherapy (TRT) as first-line treatment for ES-SCLC. With a sample size of 67 patients, it currently stands as the largest published dataset from China on immuno-chemotherapy combined with radiotherapy in this patient population.

One major highlight of the study is its exploratory approach to TRT dosing. Patients were divided into two groups based on radiation dose: a high-dose group receiving ≥50 Gy in 25 fractions, and a low-dose group receiving ≥30 Gy in 10 fractions. This design allowed us to further explore the optimal radiation dose in the context of immuno-chemotherapy for ES-SCLC.

According to data presented at the 2023 ASTRO Annual Meeting, while no statistically significant difference was observed in median progression-free survival (mPFS) between the two dose groups, there was a trend favoring the low-dose TRT group, with mPFS reaching 10.4 months compared to 7.0 months in the high-dose group.

What makes this study particularly noteworthy are the exceptional survival outcomes. The addition of thoracic radiotherapy in the era of immunotherapy significantly improved both short- and long-term outcomes for ES-SCLC patients. The median overall survival (mOS) reached 21.4 months, and the mPFS reached 10.1 months—both of which set new benchmarks for first-line immunotherapy in ES-SCLC.

In terms of objective response rate (ORR) and disease control rate (DCR), the results were also outstanding. Importantly, the regimen demonstrated a favorable safety profile, with the incidence of ≥Grade 3 pneumonitis kept to a low 6%.

This study serves as a model of translational research—from molecular discovery to clinical application. After being selected for oral presentation at the ASTRO 2023 Annual Meeting, it was once again selected for oral presentation at ASCO 2024. The international attention and recognition it has received underscore the growing scientific credibility of Chinese-led original research, particularly in the field of small cell lung cancer.

Oncology Frontier: The phase II results of this study are impressive. The addition of thoracic radiotherapy after immuno-chemotherapy appears to offer meaningful benefits in terms of both efficacy and survival in ES-SCLC. From a clinical perspective, what is the significance of these findings?

Academician Jinming Yu: Small cell lung cancer (SCLC) is characterized by aggressive behavior, rapid growth, early metastasis, and a high tendency for treatment resistance. Achieving early and effective tumor control is critical. Historically, treatment relied heavily on chemotherapy, which yielded poor outcomes, with overall survival typically limited to 8–10 months.

Although the advent of immunotherapy has led to significant advances in SCLC treatment, we are now approaching a plateau in survival benefits. The urgent question is how to further improve outcomes.

This phase II study of Adebrelimab combined with chemotherapy followed by thoracic radiotherapy produced remarkable results, with a median progression-free survival (mPFS) of 10.1 months and a median overall survival (mOS) of 21.4 months. These data provide preliminary confirmation that adding thoracic radiotherapy in the first-line treatment setting can delay disease recurrence—particularly in patients who may develop early resistance to immunotherapy—and significantly extend survival.

Importantly, this approach demonstrated a favorable safety profile and good accessibility in real-world practice.

Given these findings, this combination strategy represents a highly promising treatment model for ES-SCLC. It holds the potential to further prolong survival and redefine the standard of care. I believe it will continue to shape the future of ES-SCLC management and help usher in a new era of long-term survival for patients with this difficult-to-treat disease.

Oncology Frontier: Previously, median overall survival for ES-SCLC with first-line immuno-chemotherapy has hovered around 15 months. In this study, the addition of thoracic radiotherapy further extended survival. Could you elaborate on the clinical value of radiotherapy in the treatment of SCLC?

Academician Jinming Yu: Radiotherapy, alongside surgery and chemotherapy, is one of the three main pillars of cancer treatment. In the comprehensive management of SCLC—particularly extensive-stage SCLC (ES-SCLC)—radiotherapy plays a critical role.

The phase III CREST trial demonstrated that for patients who achieved a response after chemotherapy, consolidative thoracic radiotherapy led to further improvements in both progression-free and overall survival. This laid an important foundation for integrating radiotherapy into ES-SCLC care.

SCLC, however, poses unique challenges in immunotherapy. The response rates to immune checkpoint inhibitors remain modest, likely due to the tumor’s biological characteristics—such as low PD-L1 expression and the presence of immunosuppressive factors in the tumor microenvironment.

Radiotherapy may help overcome these barriers. Both preclinical and exploratory phase II studies suggest that radiotherapy can upregulate PD-L1 expression, enhance immune infiltration, and reshape the tumor microenvironment. In doing so, radiotherapy can effectively transform so-called “cold tumors” into “hot tumors”, thereby improving the efficacy of immunotherapy. This synergy highlights radiotherapy’s evolving role—not just as a local modality, but also as a potentiator of systemic immune response in SCLC.

Oncology Frontier: Looking ahead, what are the key directions for combining immunotherapy with radiotherapy in SCLC?

Academician Jinming Yu: There is still substantial room for optimization in combining radiotherapy, chemoradiotherapy, and immunotherapy in SCLC.

For different stages of the disease, determining the optimal combination strategies and radiation doses remains a critical area of future research. We also need to identify the subgroups of patients most likely to benefit, along with biomarkers that can predict response and prognosis.

Moreover, most of the current studies on immuno-radiotherapy use photon-based radiation. However, emerging modalities like proton therapy or heavy ion radiotherapy may interact with the immune system differently. Understanding how these advanced technologies affect the tumor immune microenvironment—and how they can be combined with immunotherapy—represents a highly promising direction for future exploration.

President of Shandong Cancer Hospital Academician of the Chinese Academy of Engineering, Doctor of Medicine, Doctoral Supervisor Representative to the 17th National Congress of the Communist Party of China, National Model Worker Deputy to the 10th, 12th, 13th, and 14th National People’s Congress Honorary President of Shandong First Medical University (Shandong Academy of Medical Sciences) President-elect of the Chinese Society of Clinical Oncology (CSCO) Chairman of the Multidisciplinary Team (MDT) Professional Committee, Chinese Anti-Cancer Association President of the Shandong Anti-Cancer Association President of the Shandong Society for Clinical Oncology President of the Shandong Academician and Expert Association President of the Shandong High-Level Talent Development Association Editor-in-Chief or Deputy Editor of multiple journals including the Chinese Journal of Cancer Prevention and Treatment