103P - Phase IIIb study of durvalumab plus platinumÐetoposide in first-line treatment of Chinese extensive-stage small-cell lung cancer (ORIENTAL): preliminary safety and efficacy results

Background

First-line durvalumab (D) plus platinum–etoposide (EP) significantly improved overall survival versus chemotherapy group in CASPIAN phase III study. We initiated a phase IIIb study to assess the safety and efficacy of D+EP in Chinese patients with ES-SCLC.

Methods

ORIENTAL is a single arm, multicenter, phase IIIb study. Treatment-naive ES-SCLC with ≥18 years of age and ECOG PS 0-2 were eligible. Durvalumab (1500 mg) was concurrently administered with first-line EP every 3 weeks for 4 to 6 cycles, followed by Durvalumab maintenance every 4 weeks until progressive disease or unacceptable toxicity. The primary endpoint was immune-mediated adverse events (imAE), the secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), overall survival (OS) and adverse events (AEs).

Results

Between Nov. 2020 and Aug. 2021, 151 eligible patients from 32 sites in China were enrolled and received study treatment. At the data cut-off (Feb. 28^th, 2022), 38 (25%) patients were still on study treatment. The median age was 66 years (range 43-82). 86.1% of patients were males, 4% were ECOG PS 2, and 13.2% had brain metastasis. The median cycle number of durvalumab was 7 (1-18). Any-cause AEs occurred in 97.4% of patients, and the incidence of imAE was 21.9% [95%CI 15.5-29.3]. AEs ≥ grade 3 occurred in 46.4% of patients, the most common ones were anemia (17.2%), platelet count decreased (7.3%), myelosuppression (6.0%), neutrophil count decreased (4.0%), white blood cell count decreased (3.3%), and hypokalemia (2.6%). There were discontinuations of study treatment in 12 patients (7.9%) and 5 deaths (3.3%) due to treatment-related AEs. ORR was 75.5% [95%CI 67.8-82.1], including two CRs. The median PFS was 6.3 months [95%CI 5.8-6.5), with a median follow-up of 5.7 months. The median OS was not reached yet [95%CI 9.6-NA].

Conclusions

ORIENTAL is the largest study to evaluate the safety and efficacy of D+EP in Chinese ES-SCLC patients to date. The preliminary safety profile and efficacy data are consistent with the CASPIAN study and support D+EP as the standard of care in ES-SCLC.

Clinical trial identification

NCT04449861.

Legal entity responsible for the study

The authors.

Funding

AstraZeneca China.

Disclosure

All authors have declared no conflicts of interest.