Durvalumab Plus Chemotherapy Showcases Sustained OS Benefit in ES-SCLC

Luis Paz-Ares, MD, PhD

The addition of durvalumab (Imfinzi) to platinum/etoposide chemotherapy continued to demonstrate an overall survival (OS) benefit over chemotherapy alone with a favorable safety profile in patients with extensive-stage small cell lung cancer (ES-SCLC), according to updated data from the phase 3 CASPIAN trial (NCT03043872) presented during the 2021 ESMO Congress.¹

At a median follow-up of 39.4 months (range, 0.1-47.5), durvalumab plus chemotherapy resulted in a median OS of 12.9 months (95% CI, 11.3-14.7) vs 10.5 months (95% CI, 9.3-11.2) with chemotherapy alone (HR, 0.71; 95% CI, 0.60-0.86; P = .0003). The survival benefit with the chemoimmunotherapy regimen continued to be consistent across the patient subgroups analyzed.

“Three times more patients were estimated to be alive at 3 years when treated with durvalumab plus platinum/etoposide chemotherapy vs platinum/etoposide chemotherapy alone, with a majority still receiving durvalumab treatment at data cutoff, further establishing [this regimen] as the standard of care for the first-line treatment of ES-SCLC,” Luis Paz-Ares, MD, head of the H12O-CNIO Lung Cancer Clinical Research Unit of the Spanish National Cancer Research Centre (CNIO), in Madrid, Spain, said during a presentation on the data.

Previously reported data from CASPIAN showed that the addition of durvalumab to chemotherapy significantly improved OS over chemotherapy alone in patients with ES-SCLC (HR, 0.73; 95% CI, 0.59-0.91; P = .0047). This benefit was sustained with more than 2 years of median follow-up.2 Additionally, a numerical improvement in OS was observed with the addition of tremelimumab to durvalumab plus chemotherapy vs chemotherapy alone (P = .0451), but the regimen did not meet the criteria for statistical significance (P < .0418).³

During the 2021 ESMO Congress, investigators presented the updated OS analysis for patients on the CASPIAN trial who had a median follow-up of more than 3 years.

The phase 3, global, randomized, open-label, active-controlled, multicenter CASPIAN study enrolled treatment-naïve patients with ES-SCLC who had a World Health Organization performance status of 0 or 1, a life expectancy of at least 12 weeks, and measurable disease per RECIST v1.1 criteria. Notably, patients with asymptomatic or treated and stable brain metastases were allowed to enroll on the study.

A total of 805 patients were randomized 1:1:1 to receive either durvalumab plus platinum/etoposide chemotherapy every 3 weeks for 4 cycles, durvalumab plus tremelimumab and platinum/etoposide chemotherapy every 3 weeks for 4 cycles, or platinum/etoposide chemotherapy alone every 3 weeks for 6 cycles. In the durvalumab combination arms, patients went on to receive durvalumab alone every 4 weeks until disease progression. Those in the control arm had the option to go on to receive prophylactic cranial irradiation.

Patients were stratified by the planned platinum chemotherapy they received (carboplatin vs cisplatin).

The primary end point of the trial was OS, and secondary end points included progression-free survival (PFS), overall response rate (ORR), safety and tolerability, and patient-reported outcomes.

This updated OS analysis was a planned exploratory analysis. PFS and ORR data have not been collected since the previous data cutoff. Serious adverse effects (AEs), including deaths, were analyzed, although other safety data were not collected.

Additional data showed that the OS rates at 12 months in the investigative and control arms, respectively, were 52.8% and 39.3%, respectively; at 18 months, these rates were 32.0% vs 24.8%, respectively. Moreover, at 24 and 36 months, these rates were 22.9% and 13.9%, respectively, and 17.6% and 5.8%, respectively.

Moreover, the 3-year median OS with durvalumab plus tremelimumab and chemotherapy was 10.4 months (95% CI, 9.5-12.0) vs 10.5 months (95% CI, 9.3-11.2) with chemotherapy alone (HR, 0.81; 95% CI, 0.67-0.97, P = .0200).

The OS rates in the investigative arms at 12 months and 18 months were 43.5% and 39.3%, respectively, and 30.6% and 24.8%, respectively. At 24 months and 36 months, these rates were 22.9% and 13.9%, respectively, and 15.3% and 5.8%, respectively. The benefit with the durvalumab combination over chemotherapy alone was consistent across all subsets examined.

At the data cutoff of March 22, 2021, 10.2% of patients in the durvalumab/chemotherapy arm (n = 265) were still receiving treatment, along with 7.1% of those in the durvalumab/tremelimumab plus chemotherapy arm (n = 266). The median number of durvalumab doses in each arm was 7.0 (range, 1-52) and 6.0 (range, 1-46), respectively. The median total duration of durvalumab exposure in the investigative and control arms was 28.0 weeks (range, 0.3-198.7) and 24.1 weeks (range, 0.1-190.0), respectively.

In terms of safety, the rates of serious AEs were similar in the durvalumab/chemotherapy and chemotherapy-alone arms, at 32.5% and 36.5% respectively, and the highest rates of serious AEs were reported in the tremelimumab arm (47.4%). Treatment-related AEs leading to death occurred in 2.3% of patients in the durvalumab/chemotherapy arm, 4.5% of those in the tremelimumab arm, and 0.8% in the chemotherapy arm.

References

1. Paz-Ares L, Chen Y, Reinmuth N, et al. Durvalumab _ tremelimumab + platinum-etoposide in first-line extensive-stage SCLC (ES-SCLC): 3-year overall survival update from the Phase 3 CASPIAN study. Presented at: 2021 ESMO Congress; September 16-21, 2021; Virtual. Abstract LBA61.
2. Paz-Arez 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;394(10212):1929-1939. doi:0.1016/S0140-6736(19)32222-6
3. Goldman J, 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. 2021;22(1): 51-65. doi:10.1016/S1470-2045(20)30539-8