Radiation, Durvalumab, and Chemo Improve Survival in ES-SCLC


Adding low-dose radiotherapy to standard-of-care durvalumab and chemotherapy led to survival benefits among patients with extensive-stage small cell lung cancer.

Image of small cell lung cancer

Concurrent low-dose radiotherapy (LDRT) plus durvalumab (Imfinzi) and etoposide/platinum chemotherapy led to a longer median progression-free survival (PFS) in patients with first-line extensive-stage small cell lung cancer (ES-SCLC), according to findings from the phase 2 LEAD study (NCT05092412) presented at the 2024 European Lung Cancer Congress.1

The phase 3 CASPIAN study (NCT03043872) identified durvalumab plus etoposide/platinum chemotherapy as a standard of care in ES-SCLC; however, many patients do not receive a durable clinical benefit from this combination. Investigators of the phase 2 LEAD study sought to evaluate LDRT as a means of local control and its synergistic efficacy with immune checkpoint inhibitors.

At a median follow-up for PFS of 17.3 months, the median PFS was 8.3 months (95% CI, 4.6-15.2), and the median overall survival (OS) was not reached (95% CI, 10.8-not evaluable). The 6-month and 12-month PFS rates were 57% and 40%, respectively. The overall response rate (ORR) was 87% among the 30 eligible patients who were enrolled in the study, and patients with liver and brain metastases had an ORR of 50% and 100%, respectively. The median duration of response was 7.0 months (range, 3.3-13.7).

These findings warrant further evaluation of this regimen, according to Yan Zhang, MD, PhD, Sichuan University in Chengdu, China, who presented the data.

Regarding safety, grade 3 or higher treatment-emergent adverse events (AEs) were observed in 80% (n = 24) of patients, and hematologic toxicity was the most common. Grade 3 or higher immune-related AEs were observed in 13.3% (n = 4) of patients. Serious AEs related to radiation were reported in 5 patients (16.7%). Three treatment-emergent AEs were fatal but considered unrelated to treatment, and 13.3% of patients discontinued treatment due to AEs.

The study’s primary end point was PFS, and secondary end points included OS, PFS at 6 months, PFS at 12 months, and safety.

Patients with treatment-naive ES-SCLC were included in the study, and patients with asymptomatic or treated and stable brain metastases were eligible for enrollment. Patients needed to have a life expectancy of at least 12 weeks and an ECOG performance status of 0 to 1.

The median patient age was 58 years (range, 40-77), 96.7% of patients were men, and 83.3% were current smokers. Three patients (10%) had brain or central nervous system metastases.

Treatment consisted of LDRT 15 Gy/5f daily plus durvalumab 1500 mg every 3 weeks and 4 cycles of etoposide plus cisplatin or carboplatin. Patients then continued to receive 1500 mg of durvalumab every 4 weeks plus LDRT until progressive disease or unacceptable toxicity were observed.

1. Zhang Y. Phase II study of low-dose radiation (LDRT) plus durvalumab (D) and etoposide/platinum (EP) as first-line treatment in ES-SCLC (LEAD): efficacy and safety results. Presented at: 2024 European Lung Cancer Congress. March 20-23, 2024. Prague, Czech Republic. Abstract 194MO.
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