KEY TAKEAWAYS
- The LEAD phase II trial aimed to investigate LDRT plus D and EP as 1L treatment for ES-SCLC patients.
- The primary endpoint was PFS.
- The promising outcomes of LDRT with D + EP in 1L ES-SCLC in the LEAD study necessitate further investigation.
Despite durvalumab (D) + etoposide/platinum (EP) being established as first-line (1L) standard of care for extensive stage small cell lung cancer (ES-SCLC) by the phase III CASPIAN trial, durable clinical benefit remains elusive for most patients. Low-dose radiation (LDRT) has potential to enhance local control and synergize with immune checkpoint inhibitors.
Y. Zhang and the team aimed to assess the efficacy of LDRT combined with D and EP as 1L treatment for patients with ES-SCLC.
The study enrolled treatment-naïve patients aged ≥18 with ES-SCLC and ECOG PS 0-1. Patients received D (1500 mg) plus EP every 3 weeks for 4 cycles, followed by D maintenance. Concurrent LDRT (15 Gy/5 fractions) was administered during the first cycle. Prophylactic cranial radiation (PCI) was allowed at the investigator’s discretion. The primary endpoint was progression-free survival (PFS), with secondary endpoints including overall survival (OS) and safety.
About 30 eligible patients were enrolled across 4 sites in China. As of the November 9th, 2023 data cut-off, the median age was 58 years (range 40-77), with 97% (29) being male. Approximately 60% (17) of patients had an ECOG PS of 1. Baseline liver and brain metastases were observed in 20% (6) and 10% (3) of patients, respectively and 57% (17) underwent PCI.
Median follow-up for PFS in censored patients was 17.3 months. PFS events occurred in 73% (22) of patients. The median (mPFS) was 8.3 months (95% CI 4.6-15.2), with 6-month and 12-month PFS rates of 57% and 40%, respectively. The median OS was not reached (95% CI 10.8m-NE). The overall objective response rate (ORR) was 87%. Among patients with liver and brain metastases, the ORR was 50% and 100%, respectively.
Grade (G) ≥ 3 treatment-emergent adverse events (TEAEs) occurred in 80% (24) of patients, with hematological toxicity being the most common. G ≥ 3 immune-related adverse events (irAEs) were reported in 13.3% (4) of patients. The incidence of radiation-related serious adverse events (SAEs) was 16.7% (5). One patient experienced interstitial lung disease (G2).
At the data cut-off, 33.3% (10) of patients were still receiving treatment, with further assessment ongoing.
The LEAD study revealed encouragingly prolonged median PFS and favorable tolerability with concurrent LDRT and D + EP in first-line ES-SCLC treatment, suggesting the need for continued exploration of this therapeutic approach.
The trial was sponsored by You Lu.
Source: https://rb.gy/9zyxrc
Clinical Trial: https://clinicaltrials.gov/study/NCT05092412
Y. Zhang, Y. Xie, Y. Gong, et al. (2024) “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 ELCC 2024. Annals of Oncology (2024) 9 (suppl_3): 1-11. 10.1016/esmoop/esmoop102577 (194 MO).
