Chemoimmunotherapy Shows Promise for Limited-Stage SCLC in Real-World Study

A new real-world study found promising evidence for combining platinum-based chemotherapy with a programmed death-1 (PD-1) inhibitor, showing that the approach is both feasible and effective for patients with recurrent limited-disease small cell lung cancer (LD-SCLC) following chemoradiotherapy (CRT).1

The introduction of PD-1 and PD-L1 inhibitors has revolutionized various cancer types, but their role in recurrent LD-SCLC has remained underexplored. This study, conducted in Japan, is among the first to assess their effectiveness post-CRT in a real-world setting and builds on prior data from the IMpower133 and CASPIAN trials, which demonstrated survival benefits with immunotherapy in newly diagnosed extensive-stage SCLC.

As SCLC continues to pose a therapeutic challenge due to rapid progression and early metastasis, the convergence of immunotherapy and precision radiation holds promise to extend survival and improve outcomes. | Image credit: mi_viri - stock.adobe.com

Published in Thoracic Cancer, the retrospective study analyzed 66 patients across 19 institutions who experienced disease recurrence after definitive CRT for LD-SCLC and were subsequently treated with platinum-etoposide chemotherapy with either atezolizumab (Tecentriq; Genentech) or durvalumab (Imfinzi; AstraZeneca).

The overall response rate was 53%, with a disease control rate of 78.7%. The median progression-free survival (PFS) was 5.9 months, and the median overall survival (OS) reached 24.9 months. Notably, patients who relapsed 12 months or more after CRT had significantly longer PFS (9.5 months) and OS (not reached), suggesting that delayed recurrence may be a favorable prognostic marker.

As SCLC continues to pose a therapeutic challenge due to rapid progression and early metastasis, the convergence of immunotherapy and precision radiation holds promise to extend survival and improve outcomes in a disease long marked by limited options.

“These findings may provide a new direction for the pharmacological management of patients with recurrent LD-SCLC,” wrote the researchers of their findings, noting, “In the future, it is necessary to conduct prospective studies on the effects of platinum, etoposide, and ICIs in patients with recurrent LD-SCLC.”

The findings coincide with ongoing developments in the field. Data released toward the end of 2024 from the phase 3 ADRIATIC trial showed that durvalumab consolidation after CRT significantly prolonged OS in LD-SCLC vs placebo (median 55.9 months [95% CI, 37.3-not reached] vs 33.4 months [95% CI, 25.5-39.9]; HR, 0.73; 98.321% CI, 0.54-0.98; P = .01), strengthening the rationale for integrating immunotherapy earlier in the treatment course.2

In this real-world study, treatment-related toxicities were consistent with known profiles of chemotherapy and PD-1 inhibitors.1 Grade ≥3 neutropenia occurred in 65.2% of patients, while febrile neutropenia was reported in 10.6%. Immune-related adverse events were rare and mostly low grade. No treatment-related deaths were observed, and there were 4 patients who discontinued treatment due to side effects, including from carboplatin allergy, colitis, pneumonitis, and pneumonia caused by COVID-19.

Atezolizumab was used in approximately 70% of patients, with the remainder receiving durvalumab. Most patients completed 4 cycles of chemotherapy, followed by maintenance immunotherapy. Physicians selected patients for immunotherapy based on clinical judgment, which may introduce selection bias. Additionally, the group noted that the study’s retrospective design, lack of a control group, and modest sample size limit generalizability.

Multivariable analysis revealed several factors associated with poorer outcomes, including liver metastases, brain metastases, and early relapse within 12 months of CRT. Additionally, patients treated with 3-dimensional conformal radiotherapy rather than involved-field radiotherapy demonstrated better OS, potentially due to more comprehensive nodal coverage.

The study also examined inflammatory and nutritional markers, including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, advanced lung cancer inflammation index, and prognostic nutritional index. These biomarkers may help stratify patient risk and optimize treatment decisions in future studies.

References

1. Shiono A, Imai H, Kaira K, et al. Significance of platinum-based chemotherapy with programmed death-1 blockade in limited disease small cell lung cancer: a retrospective study. 2025;16(13):e70118. doi:10.1111/1759-7714.70118

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