REAL-WORLD DURVALUMAB IN EXTENSIVE-STAGE SMALL CELL LUNG CANCER (ARAL)

REAL-WORLD CLINICAL OUTCOMES AMONG PATIENTS INCLUDED IN AN EARLY ACCESS PROGRAMME TREATED WITH DURVALUMAB IN COMBINATION WITH PLATINUM AND ETOPOSIDE AS FIRST-LINE THERAPY IN EXTENSIVE-STAGE SMALL CELL LUNG CANCER: AN ITALIAN MULTICENTER OBSERVATIONAL STUDY

Primary lung cancer is one of the most common malignancies and causes of cancer-related death worldwide [Passiglia et al., 2019; Bade and Dela Cruz, 2020].

Lung cancer is classified into different types, among which small cell lung cancer (SCLC), accounting for 13%-20% of all lung cancer cases [Pezzuto et al., 2019; Torres-Durán et al., 2021], is an aggressive form of neuroendocrine malignancy characterized by rapid growth, tendency to disseminate early and high relapse rates [El Sayed and Blais, 2021].

There are persistently limited treatment options for SCLC [DiBonaventura et al., 2019; El Sayed and Blais, 2021], and the current clinical approach to SCLC treatment is chosen irrespective of biological subtype [Rudin et al., 2021; Keogh et al., 2022]. First-line treatments for ES-SCLC have been platinum-based chemotherapy combinations for decades, without significant differences in Overall Survival (OS) between cisplatin and carboplatin, valuing flexibility in the choice of platinum agent in treatment decision making for individual patients [Dingemans et al., 2021]. However, despite the high initial response rate, the prognosis remains poor [Zhang et al., 2021; Johal et al., 2021].

In recent years, immunotherapy has dramatically modified cancer treatment across several malignancies and has been an active area of investigation in SCLC [Calles et al., 2019; Dingemans et al., 2021]. Treatments that combine chemotherapy and immune checkpoint inhibitors (ICIs), such as durvalumab and atezolizumab, can increase immune responses to tumor cells, resulting in improved efficacy in ES-SCLC compared to chemotherapy alone [Esposito et al., 2020; Konala et al., 2020; Hiddinga et al., 2021; Lim and Kang, 2021]. These treatment regimens have been approved in many countries [Wang et al., 2022] and are now the standard of care in the ES-SCLC first-line setting, according to the ESMO [Dingemans et al., 2021] and the NCCN Clinical Practice Guidelines in Oncology [Ganti et al., 2022].

Durvalumab is a fully human, immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that selectively blocks the interaction of programmed cell death ligand-1 (PD-L1) with PD-1 and CD80 [IMFINZI® (durvalumab) Summary of Product Characteristics]. The phase III CASPIAN study (ClinicalTrials.gov identifier: NCT03043872) showed that the addition of durvalumab to a combination regimen of etoposide with either cisplatin or carboplatin significantly improved OS compared with etoposide and platinum alone, with a manageable tolerability profile [Paz-Ares et al., 2019; Goldman et al., 2021; Paz-Ares et al., 2022].

Following the CASPIAN study, an Early Access Programme (EAP) to provide pre-approval access to durvalumab plus platinum-etoposide for ES-SCLC patients eligible to receive first-line platinum-based chemotherapy (D419QR00007 EAP, hereafter called 'CASPIAN EAP') was activated in Italy in March 2020, including 125 subjects across 39 oncology centers.

Clinical trials have demonstrated significant efficacy and a favorable safety profile of durvalumab combined with chemotherapy in ES-SCLC [Paz-Ares et al., 2022]. On the other hand, it is estimated that stringent eligibility criteria may exclude up to 70% of patients with lung cancer from ICI clinical trials [von Itzstein et al., 2020]. Understanding the efficacy and safety of ICIs in a more heterogeneous patient population than in randomized controlled trials is critical to realizing the full potential of these therapies. To fill the gap between strictly controlled clinical trial populations and actual lung cancer patients managed in clinical practice, observational studies from real-world settings are emerging [von Itzstein et al., 2020]. Although real-world studies are unable to achieve the high internal validity of randomized controlled trials (RCTs), accurately performed analyses of real-world data can provide valuable complementary results [Nazha et al., 2021].

In conclusion, considering that ES-SCLC are often elderly patients with multiple comorbidities [Schulkes et al., 2016] for whom the treatment decision-making is challenging [DiBonaventura et al., 2019], the ARAL observational study will contribute to filling the information gap by collecting real-world data from the CASPIAN EAP to better describe durvalumab treatment outcomes and treatment patterns among patients diagnosed with ES-SCLC in Italy.

Study Overview

• Status: Completed
• Conditions: Small Cell Lung Carcinoma
• Intervention / Treatment: Drug: Durvalumab

• Study Type: Observational
• Enrollment (Actual): 71

Contacts and Locations

Study Locations

• Italy
  • Bologna, Italy
    • Research Site
  • Catanzaro, Italy
    • Research Site
  • Lucca, Italy
    • Research Site
  • Napoli, Italy
    • Research Site
  • Palermo, Italy
    • Research Site
  • Pistoia, Italy
    • Research Site
  • Prato, Italy
    • Research Site
  • Roma, Italy
    • Research Site
  • Trento, Italy
    • Research Site
  • Varese, Italy
    • Research Site
  • Vimercate, Italy
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study is focused on studying a cohort of adult patients diagnosed with ES-SCLC, treated with durvalumab in combination with platinum (cisplatin or carboplatin) and etoposide as first-line therapy in the context of the CASPIAN EAP implemented in Italy. Approximately 90 subjects are expected to be included across about 15 sites in Italy, during an expected inclusion period of about 8 months.

Description

Inclusion Criteria:

1. Patients with diagnosis of extensive-stage Small Cell Lung Cancer (ES-SCLC).
2. Patients entered, at least 24 months prior to the study inclusion, the D419QR00007 Early Access Programme (CASPIAN EAP) implemented in Italy.
3. Adult patients (aged ≥ 18 years) at the time of inclusion in the CASPIAN EAP.
4. Patients having performed at least one administration of durvalumab treatment in the CASPIAN EAP.
5. Patients (or their legally acceptable representatives) who have signed the subject informed consent and privacy form, if applicable.

Exclusion Criteria:

1. Patients with unavailable medical chart.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	OS rate at 12 and 18 months after index date (defined as Day 1 of Cycle 1 - C1 D1 of platinum-etoposide chemotherapy)	12 and 18 months after index date
Overall survival	Median OS	From index date to death or date of enrollment in the study (up to 5 years)
Overall Survival	Mean OS	From index date to death or date of enrollment in the study (up to 5 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	OS rate at 24 months after index date (defined as platinum-etoposide chemotherapy C1 D1).	24 months after index date
Progression Free Survival	PFS rate at 12, 18 and 24 months after index date.	12, 18, 24 months after index date
Progression free survival	Median PFS	From index date to death or progression or date of enrollment in the study (up to 5 years)
Time to discontinuation	Median TTD	From index date to last dose of treatment with durvalumab or death or date of enrollment in the study (up to 5 years)
Time to First Subsequent Therapy or Death	Median TFST	From index date to start of other cancer treatment or death or date of enrollment in the study (up to 5 years)
Pattern of relapse	Patterns of relapse after durvalumab treatment (e.g., thoracic/extra-thoracic/central nervous system - CNS relapse).	From index date to date to progression or death or date of enrollment in the study (up to 5 years)
Duration of platinum-etoposide chemotherapy	Duration of platinum-etoposide chemotherapy prior to durvalumab maintainance initiation	From index date until durvalumab maintenance initiation or death or discontinuation of treatment (up to 5 years)
durvalumab treatment duration	durvalumab treatment duration	From initiation of durvalumab until death or date of enrollment in the study (up to 5 years)
number of durvalumab administrations	number of durvalumab administrations	From initiation of durvalumab until death or date of enrollment in the study (up to 5 years)
reason for durvalumab dosage adjustment	reason for durvalumab dosage adjustment	From initiation of durvalumab until death or date of enrollment in the study (up to 5 years)
reason for temporary interruption or permanent discontinuation	reason for temporary interruption or permanent discontinuation of durvalumab, (e.g., safety event)	From initiation of durvalumab until death or date of enrollment in the study (up to 5 years)
Concomitant tratments	Details of chemotherapy (platinum-etoposide) combined with durvalumab and other concomitant treatments.	From initiation of durvalumab until death or date of enrollment in the study (up to 5 years)
Subsequent anticancer treatments	Details of subsequent anticancer treatments; treatment sequences over time for ES-SCLC.	From discontinuation of durvalumab until death or date of enrollment in the study (up to 5 years)
Adverse Event of Special interest (AESI)verbatim; severity; seriousness; causality; action taken with respect to durvalumab treatment; outcome.	To evaluate safety and tolerability profile of durvalumab + EP treatment, adverse events of special interests were assessed. An AESI is an AE of scientific and medical interest specific to understanding of the IMP.	from initiation of durvalumab until treatment discontinuation or date of enrollment in the study (up to 5 years)
Adverse Event other than AESI (limited to Adverse Drug Reaction - ADR and Serious Adverse Event - SAE, including Serious Adverse Drug Reaction - SADR) verbatim; severity; seriousness; causality; action taken with respect to durvalumab treatment; outcome.	To evaluate safety and tolerability profile of durvalumab + EP treatment, adverse events of special interests were assessed. An AESI is an AE of scientific and medical interest specific to understanding of the IMP.	from initiation of durvalumab until treatment discontinuation or date of enrollment in the study (up to 5 years)
Occurrence of at least one AESI/ ADR/ SAE/ SADR.	To describe real-world safety and tolerability of durvalumab in combination with chemotherapy as first-line treatment in the CASPIAN EAP.	from initiation of durvalumab until treatment discontinuation or date of enrollment in the study (up to 5 years)
Durvalumab temporary interruption due to AESIs/ ADRs/SAEs/SADRs.	To describe real-world safety and tolerability of durvalumab in combination with chemotherapy as first-line treatment in the CASPIAN EAP.	from initiation of durvalumab until treatment discontinuation or date of enrollment in the study (up to 5 years)
Durvalumab permanent discontinuation due to AESIs/ ADRs/SAEs/SADRs.	To describe real-world safety and tolerability of durvalumab in combination with chemotherapy as first-line treatment in the CASPIAN EAP.	from initiation of durvalumab until treatment discontinuation or date of enrollment in the study (up to 5 years)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time interval from initial diagnosis of SCLC to test execution (e.g. biomarker test, gene mutational test,histological/cytological test)	To describe testing patterns among patients diagnosed with ES-SCLC according to the standard clinical practice in Italy.	from SCLC diagnosis to test execution (up to 3 monts)
Time interval from diagnosis of extended disease to test execution (e.g. biomarker test, gene mutational test,histological/cytological confirmation)	To describe testing patterns among patients diagnosed with ES-SCLC according to the standard clinical practice in Italy.	from diagnosis of extended disease to test execution (up to 3 monts)
RR	To describe the Investigator-assessed Response Rate (RR) of ES-SCLC patients treated with durvalumab plus platinum-etoposide in a real-world setting (CASPIAN EAP).	from index date until disease progression or the last evaluable assessment (up to 5 years)

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2024
• Primary Completion (Actual): January 23, 2025
• Study Completion (Actual): January 23, 2025

Study Registration Dates

• First Submitted: February 10, 2025
• First Submitted That Met QC Criteria: February 10, 2025
• First Posted (Actual): February 14, 2025

Study Record Updates

• Last Update Posted (Actual): June 24, 2025
• Last Update Submitted That Met QC Criteria: June 18, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Small Cell Lung Carcinoma; Antineoplastic Agents, Immunological; Antineoplastic Agents; Durvalumab
• Other Study ID Numbers: D9070R00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org.

Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No