2 Immunotherapies Show Comparable Benefits in Extensive-Stage Small Cell Lung Cancer

Author(s):

Key Takeaways

PD-1 and PD-L1 inhibitors combined with chemotherapy significantly improve survival in ES-SCLC compared with chemotherapy alone.
No significant difference in overall survival or progression-free survival was found between PD-1 and PD-L1 inhibitors.
Both treatment combinations did not significantly increase severe treatment-related adverse events compared with chemotherapy alone.
Higher PD-L1 expression may slightly favor PD-1 inhibitors, while lower expression may benefit PD-L1 inhibitors, but further research is needed.

When added to chemotherapy, researchers found no significant difference in overall or progression-free survival between PD-1 and PD-L1 inhibitors.

Patients with extensive-stage small cell lung cancer (ES-SCLC) saw significant survival benefits when treated with either PD-1 or PD-L1 inhibitors combined with chemotherapy, according to a new meta-analysis.¹

radiology x-ray lung cancer | Image credit: utah51 – stock.adobe.com

Researchers found no significant difference in OS and PFS for patients with ES-SCLC. | Image credit: utah51 – stock.adobe.com

The study was published in Frontiers in Oncology and included 3559 patients with ES-SCLC across 8 randomized clinical trials (RCTs). After comparing the 2 immunotherapy approaches, researchers found no significant difference in overall survival (OS) or progression-free survival (PFS) between them.

“The present study enriched the research data on PD-1 inhibitors in the first-line treatment of ES-SCLC after the inclusion of the results of tislelizumab and toripalimab, but PD-1 + Chemo versus PD-L1 + Chemo did not produce a significant improvement in OS and PFS,” the authors said.

Patients who received PD-1 plus chemotherapy had a 29% reduced risk of death compared with those receiving chemotherapy alone, while those treated with PD-L1 plus chemotherapy saw a 28% reduction in mortality risk. Both treatment combinations significantly improved PFS, increasing by 41% with PD-1 inhibitors and 27% with PD-L1 inhibitors, compared with chemotherapy alone.

In indirect comparisons, researchers did not find a significant advantage of one inhibitor over the other in terms of efficacy (OS: HR, 0.99; 95% CI, 0.86-1.1; PFS: HR, 0.80; 95% CI, 0.61-1.0) or safety (HR, 1.0; 95% CI, 0.93-1.1) when added to chemotherapy. They noted that more research is needed to see how similar or different their efficacy and safety are in treating ES-SCLC.

Regarding safety, neither PD-1 nor PD-L1 inhibitors significantly increased the incidence of severe treatment-related adverse events (TRAEs) compared with chemotherapy alone, the authors found. The likelihood of experiencing grade 3 or higher TRAEs was nearly identical between the 2 treatments (HR, 1.0; 95% CI, 0.93-1.1), reinforcing the idea that both options provide added survival benefits without additional safety concerns. However, as PD-1 inhibitors block the interaction between PD-1 and its ligands, PD-L1 and PD-L2, the authors said the treatment option may lead to a higher incidence of AEs.²

Additionally, a subgroup analysis indicated that patients with ES-SCLC with higher PD-L1 expression levels (≥ 1%) may benefit slightly more from PD-1 inhibitors, while those with lower PD-L1 expression (< 1%) appeared to respond better to PD-L1 inhibitors.¹ However, researchers cautioned against using PD-L1 expression as a definitive marker for treatment selection until further research confirms these findings.

A 2020 meta-analysis published in Thoracic Cancer included 4 of the 8 studies analyzed—KEYNOTE-604, IMpower133, EA5161, and CASPIAN—but came to a different conclusion about safety.³

While PD-1 and PD-L1 inhibitors combined with chemotherapy significantly improved survival in ES-SCLC, they were also linked to an increased risk of immune-related AEs (imAEs). Compared with chemotherapy alone, patients who received either combination therapy saw an almost quadrupled increase in all-grade imAEs (HR, 3.77; 95% CI, 1.99-7.15; P < .0001) and a sevenfold increase in severe imAEs, defined as grade 3 or higher (HR, 7.01; 95% CI, 2.48-19.81; P = .0002).

The current study did not assess how these treatments impact quality of life, an important factor for patients.¹ According to the authors, additional research with larger, well-controlled clinical trials is needed to confirm these findings.

References

Wang K, Zheng C, Chen X, et al. Updated Bayesian network meta-analysis on the efficacy and safety of PD-1 versus PD-L1 inhibitors in first-line treatment with chemotherapy for extensive-stage small-cell lung cancer. Front Oncol. 2025;14:1455306. doi:10.3389/fonc.2024.1455306
Parvez A, Choudhary F, Mudgal P, et al. PD-1 and PD-L1: architects of immune symphony and immunotherapy breakthroughs in cancer treatment. Front Immunol. 2023;14:1296341. doi:10.3389/fimmu.2023.1296341
Zhang S, Li S, Cheng Y. Efficacy and safety of PD-1/PD-L1 inhibitor plus chemotherapy versus chemotherapy alone as first-line treatment for extensive-stage small cell lung cancer: a systematic review and meta-analysis. Thorac Cancer. 2020;11(12):3536-3546. doi:10.1111/1759-7714.13698