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Neoadjuvant immunotherapy combined with chemotherapy has demonstrated promising efficacy and an acceptable safety profile in patients with limited-stage small cell lung cancer (LS-SCLC), according to a recent meta-analysis. The findings suggest this approach could offer a new therapeutic strategy for a disease with a historically poor prognosis, particularly for patients with more advanced disease.

The meta-analysis, which pooled data from 6 studies and 114 patients, found that neoadjuvant chemoimmunotherapy led to high rates of pathological complete response (pCR) and major pathological response (MPR), key indicators of treatment effectiveness before surgery. It also confirmed that most patients undergoing this treatment were able to achieve a successful R0 surgical resection, meaning no visible or microscopic tumor was left behind.

“The current research findings demonstrate that neoadjuvant immunotherapy has shown promising clinical efficacy and acceptable safety in SCLC,” the study’s authors concluded. “These results provide valuable reference for upcoming clinical trials regarding the optimal neoadjuvant strategy and potential beneficiary populations.”

Addressing an Unmet Need in SCLC

SCLC, which accounts for 10% to 15% of all lung cancers, is notoriously aggressive, with rapid progression and a high risk of metastasis. Despite improvements in treatment, the 5-year survival rate remains under 7%. While immunotherapy has revolutionized care for extensive-stage SCLC, its role in the limited-stage setting has been less defined.

The National Comprehensive Cancer Network (NCCN) guidelines recommend surgery for early-stage (I-IIA) SCLC, with chemoradiotherapy being the standard of care for later-stage (IIB-IIIC) disease. However, outcomes remain suboptimal for locally advanced cases, highlighting a critical need for new treatment strategies. Neoadjuvant therapy, which aims to shrink tumors before surgery, has shown success in other cancer types and is now being explored as a way to improve surgical outcomes and long-term survival in SCLC.

Key Findings from the Analysis

Researchers conducted a systematic review and meta-analysis of studies published through February 10, 2025. They specifically looked at pathological response rates and safety outcomes, including R0 resection rates and treatment-related severe adverse events (tr-SAEs). All included studies were from China, which the authors noted as a limitation on the generalizability of the results. However, they pointed out that ongoing trials in other regions are expected to provide more diverse data in the future.

The pooled analysis of six studies found a pCR rate of 35% (95% CI 14%-56%) and an MPR rate of 49% (95% CI 18%-80%). In terms of safety, the pooled R0 surgical resection rate was 95% (95% CI 88%-100%), and the incidence of tr-SAEs was 44% (95% CI 13%-76%). Notably, no perioperative deaths were reported across any of the studies.

A subgroup analysis suggested a potential correlation between the number of neoadjuvant treatment cycles and pathological response. Patients who received more than 2 cycles of therapy appeared to have a higher rate of both pCR (45% vs 10%) and MPR (63% vs 0%) compared to those who received only 2 cycles. While this finding is based on a small number of studies, it points to a critical area for future research.

“With the increasing number of neoadjuvant treatment cycles, the incidence of preoperative adverse reactions may increase,” the authors wrote. “Nonetheless, most patients achieved R0 resection, with a low incidence of postoperative AEs and no perioperative mortality, indicating that the optimal neoadjuvant treatment regimen in SCLC patients remains worthy of exploration.”

The analysis also found a high objective response rate (ORR) of 91% based on RECIST 1.1 criteria, with no significant differences observed across different study types or neoadjuvant therapy cycles.

Implications for Clinical Practice and Future Research

The data from this meta-analysis supports the ongoing exploration of neoadjuvant chemoimmunotherapy as a viable option for patients with LS-SCLC. With 81% of the patients included in the analysis having stage III disease, the results are particularly relevant for this patient population, which has limited treatment options outside of chemoradiotherapy.

The findings highlight the need for further research to determine the optimal number of neoadjuvant therapy cycles, identify the best candidates for this treatment approach, and evaluate long-term survival outcomes. Several ongoing clinical trials are investigating neoadjuvant immunotherapy in SCLC, with trial NCT04539977 and ChiCTR2100042367 being two examples.

REFERENCE:Ge F, Lin G, Huo Z, et al. A Comprehensive Study on Clinical Outcomes and Safety of Neoadjuvant Immunotherapy Combined With Chemotherapy in Limited‐Stage Small Cell Lung Cancer. Thorac Cancer. 2025 Aug 11;16(15):e70125. doi: 10.1111/1759-7714.70125