Chemoimmunotherapy Elicits Survival Benefit in Older ES-SCLC Population

“Our real-world data suggest that combination immuno-chemotherapy provides a survival benefit in the [older] ES-SCLC patient population and can be considered a feasible treatment option,” according to the study authors.

Combining immunotherapy with chemotherapy can elicit a survival benefit among older patients with extensive-stage small cell lung cancer (ES-SCLC) without producing significant toxicity, according to findings from a real-world study published in BMC Cancer.¹

Across the entire patient population, the median overall survival (OS) was 12.89 months and the median progression-free survival (PFS) was 7.21 months. Additionally, the median OS was 11.44 months (95% CI, 9.47-13.41) among patients who received chemotherapy alone vs 14.20 months (95% CI, 11.64-16.76) in those who received chemotherapy plus immunotherapy. Data showed a median PFS of 6.59 months (95% CI, 5.12-8.06) vs 8.26 months (95% CI, 6.90-9.63) in each respective cohort; there was a statistically significant difference in PFS outcomes between groups (P = .02).

Of patients without baseline liver metastases (n = 92) in the chemotherapy/immunotherapy group (n = 52) and chemotherapy alone group (n = 40), the median PFS was 9.12 months vs 6.72 months (HR, 0.50; 95% CI, 0.32-0.81; P < .01) and the median OS was 16.36 months vs 11.57 months, respectively (HR, 0.69; 95% CI, 0.43-1.11; P = .13). Among 38 patients with brain metastases in the chemoimmunotherapy (n = 22) and chemotherapy alone groups (n = 16), the median PFS was 9.12 months vs 4.07 months (HR, 0.29; 95% CI, 0.14-0.60; P < .001) and the median OS was 13.25 months vs 7.61 months (HR, 0.49; 95% CI, 0.24-0.98; P = .05).

A subgroup analysis of OS outcomes showed that all groups apart from patients with diabetes and those with more than 6 cycles of chemotherapy benefitted from immunotherapy plus chemotherapy. A significant difference in outcomes was noted only among patients with brain metastases.

“Our real-world data suggest that combination immuno-chemotherapy provides a survival benefit in the [older] ES-SCLC patient population and can be considered a feasible treatment option,” lead study author Ke Zhao, from Shandong University Cancer Center at Cheeloo College of Medicine at Shandong University and the Department of Radiation Oncology at Shandong Cancer Hospital and Institute at Shandong First Medical University of Shandong Academy of Medical Sciences, wrote with coauthors.¹ “This study suggests a new way of considering follow-up treatment for [older patients with] ES-SCLC. To further clarify the efficacy of chemo-immunotherapy, a future large-scale prospective study of combination immuno-chemotherapy in the [older] ES-SCLC patient population is necessary.”

According to the study authors, immunotherapy plus chemotherapy has become a standard frontline treatment option for those with ES-SCLC.² Clinical trials assessing this combinatorial strategy in ES-SCLC, however, have included a small proportion of older patients and high or variable treatment doses. Consequently, investigators aimed to assess the efficacy of chemoimmunotherapy in an older population of patients with ES-SCLC and baseline brain and liver metastases.

The study evaluated 135 patients 70 years or older who received immunotherapy plus chemotherapy (n = 82) or chemotherapy alone (n = 53) at Shandong Cancer Hospital between May 20, 2020, and February 24, 2023. Patients received etoposide/cisplatin alone or PD-L1 or PD-1 inhibitors in combination with chemotherapy. Immunotherapy options included serplulimab (Hetronifly) at a fixed dose of 4.5 mg/kg, tislelizumab (Tevimbra) at 200 mg, durvalumab (Imfinzi) at 1500 mg, and atezolizumab (Tecentriq) at 1200 mg.

The study’s primary end points were OS and PFS. Secondary end points included adverse effects (AEs) in different patient subgroups.

The median patient age was 73 years (range, 70-82) in the chemoimmunotherapy group and 74 years (range, 70-86) in the chemotherapy alone group, with most patients being men in each cohort (85.4% vs 86.8%). Additionally, most patients in each group had a Karnofsky performance status of at least 80 (89.0% vs 88.7%), former or current smoking status (63.4% vs 69.8%), no diabetes (86.6% vs 84.9%), no liver metastases (63.4% vs 75.5%), no bone metastases (74.4% vs 60.4%), and no brain metastases (73.2% vs 69.8%).

Univariate analysis indicated that factors including patient sex, Karnofsky performance status, smoking status, liver metastasis status, and bone metastasis status significantly correlated with OS outcomes. Per multivariate analysis, the absence of liver metastases conferred a favorable prognosis for OS (HR, 0.523; 95% CI, 0.326-0.828; P = .007) whereas male sex correlated with a worse prognosis (HR, 2.783; 95% CI, 1.231-66.295; P = .014).

In the chemoimmunotherapy and chemotherapy alone groups, respectively, the most common any-grade AEs included decreased red blood cell counts (92.68% vs 79.25%), decreased lymphocyte counts (79.27% vs 71.70%), decreased leukocyte counts (68.20% vs 62.26%), and decreased neutrophil counts (67.07% vs 71.70%). The rates of grade 3 or higher toxicities did not significantly differ between treatment groups.

Among patients who received chemotherapy plus immunotherapy, grade 1 and 2 immune-related toxicities, respectively, included immune pneumonia (n = 5; n = 1), immune cardiac injury (n = 23; n = 1), and thyroid dysfunction (n = 13; n = 0). No grade 3 or higher immune-related adverse reactions occurred in the chemoimmunotherapy group.

References

1. Zhao K, Lu S, Niu J, Zhu H, Tian Y, Yu J. Real-world data on immunotherapy combined with chemotherapy in elderly patients with extensive-stage small cell lung cancer. BMC Cancer. 2025;25:467. doi:10.1186/s12885-025-13880-z
2. Yu Y, Chen K, Fan Y. Extensive-stage small-cell lung cancer: current management and future directions. Int J Cancer. 2023;152(11):2243-2256. doi:10.1002/ijc.34346