CASPIAN Update Supports Use of Durvalumab Plus Platinum-Etoposide in Frontline ES-SCLC

Updated results from the randomized, controlled, open-label phase 3 CASPIAN trial (NCT03043872) continue to support the use of durvalumab (Imfinzi) plus platinum–etoposide as a standard-of-care option for the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC).¹

In March 2020, the FDA approved durvalumab plus etoposide and either carboplatin or cisplatin for the indicated use based on the results of CASPIAN.² The recent report that was published in The Lancet Oncology serves to confirm previously reported findings.

The study randomized a total of 805 patients with treatment-naive, histologically or cytologically documented ES-SCLC and a WHO performance status of 0 or 1. Patients were randomly assigned 1:1:1 in blocks of 6 to receive either intravenous durvalumab plus tremelimumab (formerly ticilimumab; CP-674,206) plus platinum–etoposide (n = 268), durvalumab plus platinum–etoposide (n = 268), or the chemotherapy combination alone (n = 269).

The dual primary end points were overall survival (OS) for the durvalumab combination arm versus platinum–etoposide alone as well as for the durvalumab-plus-tremelimumab group versus chemotherapy in the intention-to-treat population. Safety was also assessed in all patients who received at least 1 dose of treatment.

As of the data cut-off of January 27, 2020, the median follow-up time for OS was 25.1 months (IQR, 22.3-27.9), representing an additional 11 months of follow-up compared with the interim analysis.

Overall, the updated results demonstrated that first-line durvalumab plus platinum–etoposide showed sustained OS improvement versus the control; however, the addition of tremelimumab to durvalumab plus platinum–etoposide did not significantly improve outcomes versus platinum–etoposide alone.

“These results support the use of durvalumab plus platinum–etoposide as a new standard of care for the first-line treatment of ES-SCLC, offering the flexibility of platinum choice and an every-4-weeks maintenance dosing schedule that expands treatment options for patients and physicians,” wrote the study authors.

The durvalumab plus tremelimumab triplet combination was not found to be associated with a significant improvement in OS when compared with platinum–etoposide alone (HR, 0.82; 95% CI, 0.68-1.00; P = .045); median OS was 10.4 months (95% CI, 9.6-12.0) versus 10.5 months (95% CI, 9.3–11.2), respectively.

“Although disappointing, this is consistent with findings from phase 3 studies of ipilimumab in ES-SCLC, indicating that CTLA-4 blockade might not have a substantial role in an unselected patient population in this setting,” the study authors explained.

In comparison, durvalumab plus platinum–etoposide did show sustained improvement in OS versus platinum–etoposide (HR, 0.75; 95% CI, 0.62-0.91; nominal P = .0032); median OS was 12.9 months (95% CI, 11.3-14.7) versus 10.5 months (95% CI, 9.3–11.2), respectively. The key secondary end points of progression-free survival and objective response also continued to favor durvalumab plus platinum–etoposide over platinum–etoposide alone.

Regarding safety, the most common any-cause grade 3 or higher adverse events (AEs) were neutropenia (in 32%, 24%, and 33% of patients in the durvalumab/tremelimumab, durvalumab, and control groups, respectively) and anemia (13% vs 9% vs 18%). Any-cause serious AEs were also reported in 45% of patients in the durvalumab/tremelimumab group, 32% of the durvalumab group, and 36% of the platinum–etoposide group.

Moreover, treatment-related deaths occurred in 5% of patients receiving the tremelimumab regimen (2 events each of death, febrile neutropenia, and pulmonary embolism; 1 event each of enterocolitis, general physical health deterioration and multiple organ dysfunction syndrome, pneumonia, pneumonitis and hepatitis, respiratory failure, and sudden death), 2% of patients in the durvalumab/chemotherapy group (cardiac arrest, dehydration, hepatotoxicity, interstitial lung disease, pancytopenia, and sepsis in 1 patient each), and 1% of those in the platinum–etoposide group (pancytopenia and thrombocytopenia in 1 patient each).

“Safety findings in all groups were consistent with the known safety profiles of the individual drugs,” noted the authors.

Moving forward, the investigators indicated that additional research will be necessary to determine which patient characteristics might predict long-term benefit following treatment with first-line immunotherapy and chemotherapy in ES-SCLC.

References:

1. Goldman JW, Dborkin 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 2020; published online December 4, 2020. doi: 10.1016/S1470-2045(20)30539-8

2. FDA approves durvalumab for extensive-stage small cell lung cancer. Published March 27, 2020. Accessed January 13, 2021. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-extensive-stage-small-cell-lung-cancer