Adding low-dose radiotherapy to standard-of-care durvalumab and chemotherapy led to survival benefits among patients with extensive-stage 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.
Liposomal Irinotecan Shows Comparable Efficacy With Topotecan in Relapsed SCLC
June 18th 2024While the primary end point of overall survival was not met in the phase 3 RESILIENT study, the overall response rate was 44.1% vs 21.6% with liposomal irinotecan vs topotecan in relapsed small cell lung cancer.
Read More