194MO - 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

Background

The phase III CASPIAN trial established D+ EP as first-line (1L) standard of care of ES-SCLC. However, most patients (pts) do not experience durable clinical benefit. LDRT could induce local control, and exert synergistic efficacy with Immune checkpoint inhibitors. In the LEAD study we investigated LDRT plus D and EP as 1L treatment of ES-SCLC pts.

Methods

LEAD study was a single arm, multicenter, phase II trial. Treatment-naïve ES-SCLC pts aged ≥18 with ECOG PS 0-1 were eligible. D 1500 mg + EP was administered Q3W for 4 cycles, followed by D maintenance. Concurrent LDRT (15 Gy/5 fractions) were conducted in the first cycle. Prophylactic cranial radiation (PCI) was allowed per investigator discretion. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and safety.

Results

From Mar. 2022 to Feb. 2023, 30 eligible pts were enrolled from 4 sites in China. At data cut-off (Nov. 9^th 2023), the median age was 58 years (range 40-77); 97% (29 ) pts were male. 60% (17) pts had ECOG PS of 1. Presence of liver and brain metastases at baseline were reported in 20% (6) and 10% (3) pts, respectively. 57% (17) pts underwent PCI. Median follow up for PFS in censored pts was 17.3 months (mo), PFS events occurred in 73% (22) pts. mPFS was 8.3 mo [95% CI 4.6-15.2], 6-mo and 12-mo PFS rates were 57% and 40%, respectively. mOS was not reached [95% CI 10.8m-NE]. Overall objective response rate (ORR) was 87%. Among pts with liver and brain metastases, ORR was 50% and 100% respectively. Grade (G) ≥ 3 treatment emergent adverse event (TEAE) occurred in 80% (24) pts, the most common G ≥ 3 TEAEs were hematological toxicity. G ≥ 3 immune-related AEs (irAEs) were reported in 13.3% (4) pts. Incidence of radiation-related SAEs was 16.7% (5). Interstitial lung disease occurred in 1 pt (G2). 33.3% (10) pts were still on treatment at data cut-off, further assessment is ongoing.

Conclusions

Concurrent LDRT and D+ EP demonstrated promising prolonged mPFS in 1L ES-SCLC and was well-tolerated in LEAD study. This result warrant further investigation of this treatment modality in ES-SCLC.

Clinical trial identification

NCT05092412.

Legal entity responsible for the study

West China Hospital.

Funding

AstraZeneca China.

Disclosure

All authors have declared no conflicts of interest.