CANTABRICO Trial: Safety Profile of First-Line Durvalumab Plus Platinum/Etoposide in Extensive-Stage SCLC

The majority of patients with small cell lung cancer (SCLC) present with extensive-stage disease, which is associated with poor prognosis. For these patients, the CASPIAN study demonstrated that a first-line combination regimen of durvalumab plus platinum/etoposide significantly improved overall survival versus the control group. In a real-world setting, the phase 3b, single-arm, multicenter CANTABRICO study (NCT04712903) sought to confirm the safety and effectiveness of the durvalumab + platinum/etoposide regimen in patients with extensive-stage small cell lung cancer (ES-SCLC).

The CANTABRICO study enrolled adult patients with treatment-naïve ES-SCLC, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2, and ≥1 measurable lesions from 35 sites in Spain between December 2020 and April 2021. Eligible patients received durvalumab (1500 mg) plus cisplatin or carboplatin (day 1) and etoposide (days 1-3 every 3 weeks) for 4 to 6 cycles, followed by maintenance durvalumab (every 4 weeks) until progressive disease/unacceptable toxicity. The primary end point was safety. Date of data cutoff was September 12, 2023.

A total of 101 patients were included in the study. The majority (56%) of the patients in the study were ≥65 years old, men (67%), had ECOG PS of 0-1 (94%), and were current/former smokers (98%). About a third of patients presented with liver metastasis (34%) or bone metastasis (37%), and 11% presented with brain metastasis; 10% had limited-stage disease. Forty-percent received ≥5 cycles of therapy.

Thirty-three percent of patients received 6 cycles of platinum chemotherapy plus etoposide and 80% started durvalumab monotherapy. Treatment-emergent adverse events (AEs) were reported in 99% of patients; of these, grade 3-4 AEs occurred in 76% of patients, which led to discontinuation in 8% of patients. Neutropenia (22%) and anemia (25%) were the most common grade 3-4 AEs. Deaths due to any-cause AEs were reported in 8 patients; the causes of death were respiratory tract infection, hemoptysis, pneumonia, sepsis, cardiorespiratory arrest, intracranial hemorrhage, and immune-mediated neurological syndrome.

All-grade immune-mediated AEs (imAEs) were reported in 38% of patients; the most common all-grade imAEs included hypothyroidism (14%), hyperthyroidism (7%), pneumonitis (5%), and diarrhea (4%). The majority of imAEs were of grade 1-2 severity, and grade 3-5 imAEs were reported in 12% of patients; there was one death due to an imAE: immune-mediated neurological syndrome.

The authors concluded that the safety profile of the first-line durvalumab plus platinum/etoposide regimen in the real-world setting was consistent with that previously reported in the CASPIAN trial in patients with ES-SCLC, and that increasing the number of cycles of platinum/etoposide did not have a detrimental effect on safety.

Source:

Casado MDI. Phase IIIb study of durvalumab plus platinum–etoposide in first-line treatment of extensive-stage small cell lung cancer (CANTABRICO): safety results. Abstract presented at: ESMO Annual Meeting, October 20-24, 2023; Madrid, Spain. Abstract 1993P.