Neoadjuvant Immunotherapy Plus Chemotherapy Shows Promise in LS-SCLC

Neoadjuvant immunotherapy plus chemotherapy appears to be effective in patients with limited-stage small cell lung cancer (SCLC), a new report indicates. The study was published in Thoracic Cancer.¹ 

SCLC makes up only about 10-15% of lung cancer cases, the authors explained. Limited-stage cases of SCLC (LS-SCLC) make up a minority of new SCLC cases, they noted, as most patients are not diagnosed until their disease has reached extensive-stage status.

PD-1 inhibitors have shown considerable promise for patients with extensive-stage SCLC. And just last year, the ADRIATIC study (NCT03703297) suggested that the anti-PD-1 therapy durvalumab (Imfinzi; AstraZeneca) was effective as a consolidation therapy for patients with stable LS-SCLC post-concurrent chemoradiotherapy, the investigators noted.² That study was an important milestone demonstrating the efficacy of PD-1/PD-L1 inhibitors in a LS-SCLC setting, they explained.¹

The findings can help guide ongoing and future clinical trials to help solve remaining challenges in LS-SCLC. | Image credit: Jennifer - stock.adobe

In the new report, the investigators wanted to expand the knowledge base around the role of neoadjuvant immunotherapy in treating patients with LS-SCLC. To do so, they searched for existing research that included clinical outcomes and safety data for the treatment regimen. After exclusions, they analyzed a total of 6 studies with a collective patient population of 114. They then completed a meta-analysis, which showed that the pooled rates of pathological complete response (pCR) were 35% (95% CI, 14%-56%) and the major pathological response (MPR) rate was 49% (95% CI, 18%-80%).

“Notably, patients who underwent more than two neoadjuvant cycles exhibited a higher rate of pCR and MPR compared to those who received only two cycles of neoadjuvant therapy,” the authors said.

The investigators said most (95%) patients achieved R0 surgical resection (95% CI, 85%-100%). The rate of treatment-related serious adverse events was 44% (95% CI, 13%-76%). None of the studies reported patient deaths during the perioperative period.

“The safety outcomes demonstrated acceptable toxicity in neoadjuvant immunotherapy for SCLC,” the investigators wrote.

The combination of immunotherapy and chemotherapy has become a first-line treatment modality in patients with extensive-stage SCLC, they added.

“These findings further suggest that the application of immunotherapy combined with chemotherapy in the perioperative setting of LS-SCLC may have significant implications,” they said. This strategy might be able to reduce tumor burden, provide additional treatment opportunities for patients, and ultimately improve treatment outcomes and survival.

The authors noted that 81% of participants included in the 6 studies had stage III SCLC, suggesting that neoadjuvant immunotherapy could be a meaningful treatment option for such patients. They added that the survival benefits of the therapy were similar in patients with stage IIIA and IIIB disease.

The investigators listed several limitations to their findings. They said the number of studies and patients included in the analysis may be too small to generalize to a broad population. In addition, they noted that all of the studies included were from China, highlighting the need for similar trials in more diverse populations. They added that, given the high number of patients with stage III SCLC in the trials, their findings might be most helpful for stage III patients.

Going forward, the authors cautioned that several challenges will need to be addressed before neoadjuvant immunotherapy can become a standard treatment option in SCLC. Among the challenges is the need to gain a better understanding of how neoadjuvant immunotherapy works in patients with locally advanced SCLC. They said they hope their findings will help guide ongoing and future clinical trials to help solve those remaining challenges.

References

1. Ge F, Lin G, Huo Z, Wang Z, Sun N, He J. A comprehensive study on clinical outcomes and safety of neoadjuvant immunotherapy combined with chemotherapy in limited-stage small cell lung cancer. Thorac Cancer. 2025;16(15):e70125. doi:10.1111/1759-7714.70125

2. Cheng Y, Spigel DR, Cho BC, et al. Durvalumab after chemoradiotherapy in limited-stage small-cell lung cancer. N Engl J Med. 2024;391(14):1313-1327. doi:10.1056/NEJMoa2404873