Durvalumab Combo Enhances OS vs Chemo Alone in Treatment-Naive ES-SCLC

A 10% improvement in OS rate was observed with durvalumab at 27 months, with rates of 20.7% and 9.3% in the combination and EP-only arms.

First-line durvalumab (Imfinzi) plus etoposide and either carboplatin or cisplatin (EP) produced a significant improvement in overall survival (OS) compared with EP alone for patients with extensive-stage small cell lung cancer (ES-SCLC), according to results from an exploratory analysis of the phase 3 CASPIAN study (NCT03043872) published in Clinical Lung Cancer.¹

In the intention-to-treat (ITT) population (n = 537), after a median follow-up of 39.4 months, patients treated with durvalumab/EP (n = 268) exhibited a sustained OS advantage between 24 months and 36 months vs those treated with EP alone (n = 269). Furthermore, a 10% improvement in OS rate was observed with durvalumab at 27 months, with rates of 20.7% (95% CI, 16.0%-25.7%) and 9.3% (95% CI, 6.2%-13.2%) in the combination and EP-only arms, respectively.

The median OS in the respective arms was 12.9 months (95% CI, 11.3-14.7) and 10.5 months (95% CI, 9.3-11.2), with 30-, 33-, and 36-month rates of 19.1% (95% CI, 14.6%-24.1%) vs 7.4% (95% CI, 4.6%-10.9%), 17.6% (95% CI, 13.3%-22.4%) vs 6.6% (95% CI, 4.0%-10.0%), and 17.6% (95% CI, 13.3%-22.4%) vs 5.8% (95% CI, 3.4%-9.1%).

In patients younger than 70 years (n = 433), the HR for death with durvalumab/EP vs EP alone was 0.71 (95% CI, 0.58-0.88) and 0.74 in those 70 years or older (n = 104; 95% CI, 0.49-1.11). The median OS in the cohort of patients younger than 70 years was 12.9 months (95% CI, 11.4-14.9) with durvalumab vs 10.5 months (95% CI, 9.3-11.2) with EP alone, with 36-month OS rates of 18.0% (95% CI, 13.2%-23.5%) and 6.8% (95% CI, 3.9%-10.7%). In the cohort of patients 70 years or older, the median OS was 12.0 months (95% CI, 8.1-14.8) vs 10.2 months (95% CI, 7.2-13.9), with respective 36-month rates of 15.7% (95% CI, 7.3%-26.9%) and 2.0% (95% CI, 0.2%-9.1%).

“Durvalumab plus EP vs EP alone significantly prolonged survival in patients with ES-SCLC and was generally well tolerated across clinically relevant subgroups while delaying worsening of patient-reported symptoms, functioning, and health-related quality of life [HRQOL] across age subgroups,” lead author Niels Reinmuth, MD, thoracic oncologist at the Asklepios Lung Clinic and member of the German Center for Lung Research in Munich, Germany, wrote in the publication with study coinvestigators.¹ “These findings further support the use of durvalumab plus EP as first-line standard of care for patients with ES-SCLC. Further investigation in [older] patients would be beneficial given the typically small size of this population in clinical trials.”

The phase 3 CASPIAN trial enrolled patients 18 years or older with cytologically confirmed ES-SCLC and randomly assigned them 1:1:1 to receive durvalumab plus EP, durvalumab plus tremelimumab-actl (Imjudo) and EP, or EP alone. Patients were stratified by planned platinum-containing agent—cisplatin or carboplatin—and patients with brain metastases were permitted if they were asymptomatic or treated and stable.

Those in the immunotherapy arms received 1500 mg of durvalumab with or without 75 mg of tremelimumab and EP every 3 weeks for a maximum of 4 cycles followed by 1500 mg of durvalumab as maintenance every 4 weeks. In the EP-only arm, a maximum of 6 cycles could be given in addition to prophylactic cranial irritation after chemotherapy, dependent on the investigator’s discretion. Additionally, treatment could be given beyond disease progression if there was evidence of clinical benefit and treatment continued until disease progression, unacceptable toxicity, or other discontinuation criteria were met.

In the durvalumab and EP arms of the ITT population, the median age was 62.0 years (range, 28-82) and 63.0 years (range, 35-82), with most patients being younger than 65 years (62.3% vs 58.4%), male (70.9% vs 68.4%), and White (85.4% vs 82.2%). Additionally, most patients had a World Health Organization performance status of 1 (63.1% vs 66.5%) and had formerly smoked (47.0% vs 47.6%). Brain metastases were present in 10.4% and 10.0% of each arm, and liver metastases were present in 40.3% vs 38.7% of patients.

The primary end point of this analysis was OS in the durvalumab/EP and EP-alone arms of the ITT population. Secondary end points included investigator-assessed progression-free survival and objective response rate per RECIST v1.1 criteria, safety and tolerability, and HRQOL.

Grade 3 or 4 adverse effects (AEs) occurred in 62.3% and 62.8% of the durvalumab combination and EP-only groups in the ITT population, with 4.9% vs 5.6% having AEs resulting in death. Serious AEs occurred in 32.1% and 36.5% of patients, respectively, with AE-related discontinuations occurring in 10.2% and 9.4% of each arm. Immune-mediated AEs (imAEs) were reported in 20.0% and 2.6% of each respective arm, with 2.6% vs 0.8% of patients experiencing serious imAEs.

In the EP arm, the incidence of grade 3 or 4 AEs was 73.1% in the group of patients 70 years or older vs 60.3% in the group of patients younger than 70 years. With the addition of durvalumab, the rates were 66.7% and 61.2%, respectively.

Durvalumab plus EP previously received FDA approval as a frontline treatment for patients with ES-SCLC in January 2020 based on the phase 3 CASPIAN trial results.²

References

1. Reinmuth N, Goldman JW, Chen Y, et al. Durvalumab plus platinum-etoposide in extensive-stage small-cell lung cancer: outcomes in age, sex, and platinum subgroups from the phase 3 CASPIAN study. Clin Lung Cancer. Published online August 2, 2025. doi:10.1016/j.cllc.2025.08.001
2. FDA approves durvalumab for extensive-stage small cell lung cancer. FDA. March 27, 2020. Accessed September 5, 2025. https://tinyurl.com/3nhxdf2t