Background: EPSCCs represent rare and extremely aggressive tumors. In most cases, with widespread metastatic disease, the incidence rate is between 0.1% and 0.4%, and the median survival of less than one year. At present, chemotherapy is considered the only therapeutic strategy in the extensive stage of EPSCC. Methods/design: This is an open-label, multicenter, Italian phase II single-arm trial in which patients with extensive-stage EPSCC will receive first-line therapy with intravenously durvalumab (day 1) plus carboplatin or cisplatin, and etoposide (day 1–3) every 3 weeks for 4 or 6 cycles, as investigator’s choice, followed by maintenance with durvalumab every 4 weeks for a maximum of 24 months. Durvalumab will be administered at a fixed dose of 1500 mg, cisplatin at 75 to 80 mg/m2 (day 1), carboplatin AUC 5–6 (day 1), and etoposide at 80–100 mg/m2 daily on days 1 to 3 every 3 weeks. The primary endpoint is the 12-month PFS. The study hypothesis is to detect an increase of at least 10% points compared to standard chemotherapy alone. Secondary endpoints include ORR, DoR, safety, and QoL. Collateral translational studies evaluate (i) whole-exome sequencing and gene expression profiling, and (ii) genetic alterations by circulating free DNA obtained from plasma samples. The trial is an ongoing enrollment; 21 of 66 planned patients have been enrolled. Discussion: Considering the efficacy of immunotherapy plus chemotherapy in extensive SCLC and the low incidence of EPSCCs that limits the conduct of randomized trials, this therapeutic approach could be considered for the first time as an agnostic indication based on tumor histology, regardless of the tumor site. The DURVASCC study aims to demonstrate the role of anti-PDL1 antibody in combination with chemotherapy in first-line therapy of ES-EPSCC patients as a histology-related agnostic choice. Trial registration: ClinicalTrials.gov: NCT06464068, June 18, 2024.
Agnostic phase II, multicenter, single-arm study with DURVAlumab plus carboplatin or cisplatin and etoposide as first-line treatment in extensive stage - Extrapulmonary Small Cell Carcinoma (EPSCC) patients - DURVASCC trial (GOIRC-01-2021)
Martinelli, Erika;
2025
Abstract
Background: EPSCCs represent rare and extremely aggressive tumors. In most cases, with widespread metastatic disease, the incidence rate is between 0.1% and 0.4%, and the median survival of less than one year. At present, chemotherapy is considered the only therapeutic strategy in the extensive stage of EPSCC. Methods/design: This is an open-label, multicenter, Italian phase II single-arm trial in which patients with extensive-stage EPSCC will receive first-line therapy with intravenously durvalumab (day 1) plus carboplatin or cisplatin, and etoposide (day 1–3) every 3 weeks for 4 or 6 cycles, as investigator’s choice, followed by maintenance with durvalumab every 4 weeks for a maximum of 24 months. Durvalumab will be administered at a fixed dose of 1500 mg, cisplatin at 75 to 80 mg/m2 (day 1), carboplatin AUC 5–6 (day 1), and etoposide at 80–100 mg/m2 daily on days 1 to 3 every 3 weeks. The primary endpoint is the 12-month PFS. The study hypothesis is to detect an increase of at least 10% points compared to standard chemotherapy alone. Secondary endpoints include ORR, DoR, safety, and QoL. Collateral translational studies evaluate (i) whole-exome sequencing and gene expression profiling, and (ii) genetic alterations by circulating free DNA obtained from plasma samples. The trial is an ongoing enrollment; 21 of 66 planned patients have been enrolled. Discussion: Considering the efficacy of immunotherapy plus chemotherapy in extensive SCLC and the low incidence of EPSCCs that limits the conduct of randomized trials, this therapeutic approach could be considered for the first time as an agnostic indication based on tumor histology, regardless of the tumor site. The DURVASCC study aims to demonstrate the role of anti-PDL1 antibody in combination with chemotherapy in first-line therapy of ES-EPSCC patients as a histology-related agnostic choice. Trial registration: ClinicalTrials.gov: NCT06464068, June 18, 2024.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
