The durable overall survival (OS) benefit and the well-tolerated safety profile of the durvalumab with EP therapy further establishes the combination as the standard of care for the first-line treatment of ES-SCLC, Luis Paz-Ares, MD, reported at the 2021 European Society for Medical Oncology Congress on Sept. 18 (abstract LBA61).
At 3 years, there is more than three times the survival in patients with durvalumab and EP versus EP, and at the same time, the adverse-event profile continues to be favorable,” said Dr. Paz-Ares of Universidad Complutense & Ciberonc, Madrid.
This is the longest follow-up reported to date for a phase 3 trial of a programmed death–ligand 1 inhibitor and EP in this setting, he said.
The CASPIAN trial included 805 treatment-naive patients with ES-SCLC who were randomized 1:1:1 to receive 1,500 mg of durvalumab with EP every 3 weeks, 1,500 mg of durvalumab at 75 mg of tremelimumab and EP every 3 weeks, or EP alone. Patients in the durvalumab arms received four cycles of treatment followed by maintenance durvalumab, and those in the EP-only arm received up to six cycles of EP.
Primary outcomes data from the trial showed a significant overall survival benefit with durvalumab and EP versus EP alone (hazard ratio, 0.73), as did a subsequent analysis after a median follow-up of 25.1 mo (HR, 0.75).
Durvalumab with tremelimumab and EP numerically improved overall survival versus EP (HR, 0.82), but did not reach statistical significance.
At median follow up of 39.4 months, the durvalumab and EP combination showed sustained improvement in overall survival versus EP alone (HR, 0.71).
Median overall survival was 12.9 versus 10.5 months. OS was 22.9% versus 13.9% at 24 months, and 17.6% versus 5.8% at 36 months with durvalumab with EP versus EP, respectively, Dr. Paz-Ares said.
Durvalumab plus tremelimumab plus EP continued to numerically improve overall survival, compared with EP alone (HR, 0.81); median OS in that arm was 10.4 months, and 15.3% of patients were alive at 36 months, he noted.
Serious adverse events occurred in 32.5%, 47.4%, and 36.5% of patients in the durvalumab with EP, durvalumab plus tremelimumab plus EP, and EP arms respectively, and adverse events leading to death occurred in 5.3%, 10.9%, and 6.0%, respectively.
The findings are “really encouraging and unprecedented, frankly,” said session chair Alfredo Addeo, MD, of University Hospital, Geneva.
“They are setting the bar for competitors,” he said, referencing the IMpower 133 trial looking at atezolizumab with chemotherapy in ES-SCLC.
The CASPIAN study was funded by AstraZeneca. Dr. Paz-Ares reported relationships with multiple pharmaceutical companies.