|The following article features coverage from the European Society for Medical Oncology (ESMO) Congress 2021. Click here to read more of Cancer Therapy Advisor’s conference coverage.|
An extended follow-up of the phase 3 CASPIAN study demonstrated sustained overall survival (OS) benefit with durvalumab plus etoposide with either cisplatin or carboplatin (EP) compared with EP alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) in the first-line setting.1
However, the addition of tremelimumab to durvalumab plus EP did not show a significant improvement in OS in this patient population.
The results were presented at the European Society for Medical Oncology (ESMO) Congress 2021 by Luis Paz-Ares, MD, PhD, a medical oncologist at Hospital Universitario 12 de Octubre in Madrid, Spain.
Dr Paz-Ares noted that, with a median follow-up of more than 2 years (data cutoff March 11, 2019), durvalumab plus EP had shown a significant improvement in OS compared with EP (hazard ratio [HR], 0.73; 95% CI 0.59-0.91; P =.0047).2
Durvalumab plus tremelimumab plus EP had shown a numerical improvement in OS compared with EP (P =.0451) but did not meet the criteria for statistical significance (P <.0418).3
An updated OS analysis after a median follow-up of more than 3 years (39.4 months; 86% maturity; data cutoff March 27, 2021) demonstrated continued improvement in OS with durvalumab plus EP compared with EP alone — 12.9 months and 10.5 months, respectively (HR, 0.71; 95% CI, 0.60-0.86; nominal P value =.0003).
This updated OS analysis from the CASPIAN study has the longest median follow-up reported to date for a phase 3 trial of EP plus anti-PD-L1 in patients with ES-SCLC, Dr Paz-Ares said.
The global, phase 3, randomized CASPIAN trial (ClinicalTrials.gov Identifier: NCT03043872) included 805 treatment-naïve patients with ES-SCLC. The patients were randomly assigned 1:1:1 to receive durvalumab plus EP, durvalumab plus tremelimumab plus EP, or EP.
At 24 and 36 months, 22.9% and 17.6% of patients were alive in the durvalumab plus EP arm compared with 13.9% and 5.8% of the surviving patients in the EP arm, respectively.
During the long-term follow-up, although durvalumab-tremelimumab plus EP continued to numerically improve OS compared with EP (HR, 0.81; 95% CI, 0.67-0.97; nominal P =.02), it did not reach statistical significance.
The median OS was 10.4 months and 15.3% of patients were alive at 36 months in the durvalumab-tremelimumab plus EP arm.
At the data cutoff point, 46 patients were still receiving treatment with durvalumab (27 in the durvalumab plus EP arm and 19 in the durvalumab-tremelimumab plus EP arm).
Serious adverse events (AEs) from all causes occurred in 32.5% of patients in the durvalumab plus EP arm, 47.4% of patients in the durvalumab-tremelimumab plus EP arm, and 36.5% of patients in the EP arm.
With the extended follow-up, durvalumab plus EP showed a well-tolerated safety profile consistent with the previous analyses.
AEs leading to death were lowest in the durvalumab plus EP arm (5.3%), followed by EP (6.0%) and the durvalumab-tremelimumab plus EP arm (10.9%).
“Approximately 3 times more patients were estimated to be alive at 3 years when treated with [durvalumab] plus EP compared with EP alone, further establishing durvalumab plus EP as [the] standard of care for first-line treatment of ES-SCLC,” Dr Paz-Ares said.
Disclosures: This research was supported by AstraZeneca. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
- Paz-Ares L, Chen Y, Reinmuth N, et al. Durvalumab ± tremelimumab + platinum-etoposide in firstline extensive-stage SCLC (ES-SCLC): 3-year overall survival update from the phase III CASPIAN study. Presented at: European Society for Medical Oncology (ESMO) Congress 2021; September 16-21, 2021. Abstract LBA61.
- Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019. doi: 10.1016/S0140-6736(19)32222-6
- Goldman JW, Dvorkin M, Chen Y et al. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021. doi: 10.1016/S1470-2045(20)30539-8