FDA Approves Durvalumab for Extensive-Stage Small Cell Lung Cancer

Efficacy of the combination in patients with previously untreated ES-SCLC was investigated in CASPIAN (NCT03043872), a randomized, multicenter, active-controlled, open-label, trial. The evaluation was based on comparison of patients randomized to durvalumab plus chemotherapy versus chemotherapy alone. The major efficacy outcome measure was overall survival (OS). Additional efficacy outcome measures were investigator-assessed progression-free survival (PFS) and objective response rate (ORR), per RECIST v1.1.  

Median OS was 13 months (95% confidence interval [CI] = 11.5, 14.8) in the durvalumab plus chemotherapy arm compared with 10 months (95% CI = 9.3, 11.2)  in the chemotherapy alone arm (hazard ratio [HR] 0.73; 95% CI = 0.59, 0.91; p = 0.0047). 

Investigator-assessed PFS (96% of total planned events) showed a HR of 0.78 (95% CI = 0.65, 0.94), with median PFS of 5.1 months (95% CI = 4.7, 6.2) in the durvalumab plus chemotherapy arm and 5.4 months (95% CI = 4.8, 6.2) in the chemotherapy-alone arm. The investigator-assessed confirmed ORR was 68% (95% CI = 62%, 73%) in the durvalumab plus chemotherapy arm and 58% (95% CI = 52%, 63%) in the chemotherapy-alone arm. 

The most common adverse reactions (greater than 20%) in patients with ES-SCLC were nausea, fatigue  and asthenia, and alopecia. 

For ES-SCLC, durvalumab is administered prior to chemotherapy on the same day. The recommended durvalumab dosage when administered with etoposide and either carboplatin or cisplatin is 1,500 mg every three weeks prior to chemotherapy and then every four weeks as a single agent. 

This review used the Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid), a voluntary submission from to facilitate FDA’s assessment. 

FDA granted the application priority review and gave durvalumab orphan drug designation for the indication. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics). 

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) Reporting System or by calling 800-FDA-1088. 

For assistance with single-patient oncology investigational new drugs, healthcare professionals should contact the Oncology Center of Excellence’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.