The FDA has granted a priority review designation to a supplemental Biologics License Application for durvalumab for the frontline treatment of patients with extensive-stage small cell lung cancer.
The FDA has granted a priority review designation to a supplemental Biologics License Application (sBLA) for durvalumab (Imfinzi) for the frontline treatment of patients with extensive-stage small cell lung cancer (ES-SCLC).1
The sBLA is based on findings from phase III CASPIAN trial, in which adding the PD-L1 inhibitor to chemotherapy reduced the risk of death by 27% compared with chemotherapy alone (HR, 0.73; 95% CI, 0.591-0.909; P = .0047). The median overall survival (OS) increased from 10.3 months (95% CI, 9.3-11.2) with etoposide/platinum chemotherapy alone to 13.0 months (95% CI, 11.5-14.8) with the addition of durvalumab.
The CASPIAN trial evaluated durvalumab with or without the CTLA-4 inhibitor tremelimumab plus chemotherapy. Both arms were compared with platinum/etoposide chemotherapy alone. Patients assigned to chemotherapy alone could undergo prophylactic cranial irradiation (PCI) at their treating physician’s discretion. An interim analysis showed a significant advantage for the durvalumab/chemotherapy arm (without tremelimumab) versus chemotherapy alone. Follow-up continues in the tremelimumab arm.
The interim analysis included 268 patients randomized to durvalumab/chemotherapy and 269 treated with chemotherapy alone. The patients had a median age of about 62 years, men accounted for about 70% of the patients, about 45% were current smokers, about 47% were former smokers, and 10% of the patients had brain or CNS metastases. PCI was administered to 8% of patients in the etoposide/platinum arm.
The 12-month OS rate was 53.7% in the durvalumab arm and 39.8% with chemotherapy alone, and the 18-month OS rate was 33.9% with durvalumab and 24.7% without. Subgroup analysis demonstrated a consistent benefit for the durvalumab/chemotherapy arm.
The median progression-free survival (PFS) was similar between the 2 arms (5.1 months with durvalumab, 5.4 months without). Analysis of the 12-month PFS rate showed a large advantage favoring durvalumab (17.5% vs 4.7%).
The objective response rates were 67.9% for the durvalumab plus chemotherapy group and 57.6% for patients who received only chemotherapy, representing a 56% increase in the likelihood of response with the addition of durvalumab to chemotherapy. The median duration of response was identical in the 2 treatment arms (5.1 months), but 12-month response rates were 22.7% with durvalumab versus 6.3% with chemotherapy alone.
The 2 treatment arms had similar safety profiles. Any-grade all-cause adverse events (AEs), grade 3/4 AEs, serious AEs, AEs leading to treatment discontinuation, and AEs leading to death occurred in a similar proportion of patients in the 2 treatment groups. Not surprisingly, immune-related AEs occurred more often with durvalumab (19.6%) than with chemotherapy alone (2.6%).
For more than 3 decades, etoposide with cisplatin or carboplatin has represented first-line treatment for patients with ES-SCLC, and few alternatives existed. Etoposide-platinum combinations produce high initial response rates, but the responses usually are not durable. Relapse usually occurs within 6 months and median OS is about 10 months.
The CASPIAN trial, which is being conducted in over 200 location across 23 countries, is continuing until the final OS analysis for the cohort of patients receiving durvalumab plus tremelimumab and chemotherapy.
Durvalumab is approved by the FDA for the treatment of patients with locally advanced, unresectable stage III non—small cell lung cancer who have not progressed following chemoradiotherapy. The PD-L1 inhibitor also has an FDA-approved indication for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.