In a groundbreaking phase II clinical trial, researchers are exploring an innovative therapeutic strategy for extensive-stage extrapulmonary small cell carcinoma (EPSCC), a rare and highly aggressive malignancy with historically limited treatment options and dismal patient prognoses. This multicenter, single-arm study, known as the DURVASCC trial (GOIRC-01-2021), investigates the efficacy of combining durvalumab, an anti-PD-L1 immunotherapy agent, with platinum-based chemotherapy regimens to improve progression-free survival and overall outcomes for patients afflicted with this challenging disease.
EPSCCs represent a distinct subset of small cell carcinomas characterized by their occurrence outside the lungs—occurring in diverse sites such as the gastrointestinal tract, genitourinary system, and other extrapulmonary tissues. Despite their biological similarities to small cell lung cancer (SCLC), therapeutic advances for EPSCC have lagged, primarily due to its rarity and consequent difficulty in conducting robust randomized clinical trials. The median survival for patients diagnosed at the extensive stage remains under one year, emphasizing the urgent need for novel and effective treatment paradigms.
This Italian-led trial employs an open-label, single-arm design to evaluate durvalumab administered intravenously at a fixed dose of 1500 mg combined with either carboplatin or cisplatin, alongside etoposide in a 3-day schedule every three weeks. Investigators allow for a flexible chemotherapy regimen comprising four to six cycles, based on clinical judgment, followed by maintenance durvalumab dosing every four weeks, extending up to two years to sustain therapeutic benefit. Such integration of immunotherapy with established cytotoxic agents underscores a strategic shift towards harnessing the immune system’s potential in combating EPSCC’s aggressive biology.
The rationale for incorporating durvalumab stems from its mechanism as a programmed death-ligand 1 (PD-L1) inhibitor, which unleashes antitumor immunity by blocking tumor-induced immune checkpoint pathways. The success of immuno-chemotherapy combinations in extensive-stage SCLC provides a compelling precedent, suggesting this modality could represent a histology-agnostic approach applicable to EPSCC regardless of primary tumor site. This trial is poised to validate the hypothesis that an immunotherapeutic boost can translate into a clinically meaningful 10 percentage point improvement in 12-month progression-free survival compared to chemotherapy alone.
From a methodological standpoint, the trial’s primary endpoint focuses on progression-free survival at one year, reflecting rigorous criteria to capture durable disease control. Secondary endpoints such as overall response rate, duration of response, safety profile, and quality of life assessments offer a comprehensive evaluation of therapeutic impact. Additionally, the incorporation of correlative translational research aims to elucidate tumor genomics and circulating free DNA profiles through whole-exome sequencing and gene expression analyses, potentially unlocking biomarker-driven customization of future interventions.
Notably, the trial has made significant strides in recruitment, enrolling 21 patients out of its planned cohort of 66, affirming feasibility despite the low incidence of EPSCC. Multicenter collaboration across Italy demonstrates concerted efforts to overcome patient scarcity and accelerate the accrual of meaningful clinical data. These collective endeavors reflect the oncology community’s determination to innovate treatment paradigms for rare, life-threatening cancers often neglected in large-scale drug development.
The DURVASCC study embodies a paradigm shift towards agnostic therapeutic strategies centered on histological and molecular tumor characteristics rather than anatomical origin. By targeting PD-L1 in EPSCC, researchers aim to pave a path toward broader application of immunotherapy across diverse small cell carcinomas. The trial outcomes hold promise for establishing a new standard of care that can extend survival and improve quality of life in a patient population long underserved by conventional chemotherapy.
Moreover, the translational insights derived from integrated genomic profiling could illuminate mechanisms of resistance or sensitivity to immunochemotherapy, informing adaptive clinical trial designs and personalized medicine approaches. Detecting genetic alterations via circulating tumor DNA offers a minimally invasive window into tumor evolution, enabling timely adjustments to therapeutic regimens and monitoring of minimal residual disease.
Despite the enthusiasm, challenges remain in interpreting single-arm data without randomized comparators, necessitating cautious optimism and further validation in larger cohorts. Nonetheless, the study exemplifies how strategic trial designs tailored to rare cancers can yield actionable evidence expanding therapeutic horizons. The potential establishment of durvalumab plus platinum-etoposide as first-line therapy for extensive-stage EPSCC marks a hopeful milestone in an area of oncologic unmet need.
In conclusion, the DURVASCC trial represents an ambitious effort combining the immunomodulatory power of durvalumab with established chemotherapeutics to redefine first-line treatment in extensive-stage extrapulmonary small cell carcinoma. The anticipated improvements in progression-free survival and comprehensive biomarker analyses herald an era where immunotherapy transcends tumor origin boundaries, offering renewed hope to patients facing this formidable diagnosis. As recruitment continues and preliminary data emerge, the oncology community awaits with anticipation the pivotal findings that could catalyze a transformational change in managing EPSCC.
Subject of Research:
Innovative first-line treatment for extensive-stage extrapulmonary small cell carcinoma using durvalumab combined with platinum-based chemotherapy.
Article Title:
Agnostic phase II, multicenter, single-arm study with DURVA lumab plus carboplatin or cisplatin and etoposide as first-line treatment in extensive stage – Extrapulmonary Small Cell Carcinoma (EPSCC) patients – DURVASCC trial (GOIRC-01-2021)
Article References:
Damato, A., Maglietta, G., Antonuzzo, L. et al. Agnostic phase II, multicenter, single-arm study with DURVA lumab plus carboplatin or cisplatin and etoposide as first-line treatment in extensive stage – Extrapulmonary Small Cell Carcinoma (EPSCC) patients – DURVASCC trial (GOIRC-01-2021). BMC Cancer 25, 1763 (2025). https://doi.org/10.1186/s12885-025-15112-w
Image Credits:
Scienmag.com
DOI:
https://doi.org/10.1186/s12885-025-15112-w
Tags: chemotherapy and immunotherapy combinationdurvalumab immunotherapyDURVASCC clinical trialEPSCC treatment strategiesextensive-stage extrapulmonary small cell carcinomainnovative cancer therapiesmulticenter cancer studiesnovel treatment paradigms for cancerpatient survival outcomesplatinum-based chemotherapy regimensrare cancer malignanciessmall cell carcinoma research
