Durvalumab added to standard-of-care (SoC) chemotherapy demonstrated significantly improved overall survival (OS) in treatment-naive patients with extensive-stage small cell lung cancer (SCLC), according to a phase 3 study presented at the IASLC 2019 World Conference on Lung Cancer.
The CASPIAN trial was a randomized, open-label, multicenter, global, phase 3 study evaluating durvalumab in combination with SoC chemotherapy (etoposide and either cisplatin or carboplatin), or durvalumab plus tremelimumab and chemotherapy, compared with SoC chemotherapy alone. The trial consisted of experimental arms, which treated patients with durvalumab or tremelimumab with up to 4 cycles of chemotherapy, and a control arm which allowed up to 6 cycles of chemotherapy and optional prophylactic cranial irradiation. The primary efficacy end point was OS.
Preliminary results from CASPIAN showed that durvalumab in combination with 4 cycles of etoposide and platinum-based chemotherapy demonstrated a statistically significant and clinically meaningful improvement in OS compared with SoC chemotherapy alone. Patients treated with durvalumab plus chemotherapy showed a 27% reduction in the risk of death (hazard ratio [HR] 0.73, 95% CI, 0.591-0.909; P =.0047), with a median OS of 13 months compared with 10.3 months for chemotherapy-treated patients. An OS benefit with an estimated 33.9% of patients alive at 18 months after treatment was observed in the durvalumab arm vs 24.7% in the chemotherapy-alone arm.
Additionally, durvalumab plus chemotherapy showed greater benefits in secondary end points compared with SoC chemotherapy, including a higher progression-free survival (PFS) rate at 12 months (17.5% vs 4.7%), a 10.3% increase in confirmed objective response rate (67.9% vs 57.6%), and improved duration of response at 12 months (22.7% vs 6.3%).
The safety and tolerability of durvalumab plus etoposide and platinum-based chemotherapy were reported to be consistent with the safety profile observed in previous trials.
“The addition of durvalumab to EP as first-line treatment for extensive-stage non-small cell lung cancer significantly improved overall survival (27% reduction in risk of death) versus a robust control arm that permitted up to 6 cycles of etoposide. Of note, this chemo-immunotherapy regimen offers flexibility in platinum choice (carboplatin or cisplatin), reflecting current clinical practice for this challenging disease,” said Luis Paz-Ares, MD, PhD, Chair, Medical Oncology Department, Hospital Universitario Doce de Octubre, Madrid, Spain and principal investigator in the CASPIAN trial.
CASPIAN is the first study to demonstrate efficacy with the use of a fixed durvalumab dose of 1500mg given every 3 weeks plus chemotherapy for 4 cycles and then every 4 weeks until disease progression. The trial is ongoing and will continue to analyze OS data for the combination of durvalumab, tremelimumab and chemotherapy.
Durvalumab is a programmed death-ligand 1 (PD-L1) blocking antibody marketed under the brand name Imfinzi (AstraZeneca). It is currently indicated for the treatment of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after concurrent platinum-based chemotherapy and radiation, and for the treatment of locally advanced or metastatic urothelial carcinoma in patients who have disease progression during or after platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.
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Paz-Ares L, Chen Y, Reinmuth N, et al. Overall survival with durvalumab plus etoposide-platinum in first-line extensive-stage SCLC: results from the CASPIAN study. Presented at: The IASLC 2019 World Conference on Lung Cancer (WCLC) of the International Association for the Study of Lung Cancer; September 7-10, 2019; Barcelona Spain. Abstract PL02.11.