Study type

Study topic

Disease /health condition
Human medicinal product

Study type

Non-interventional study

Scope of the study

Effectiveness study (incl. comparative)

Data collection methods

Primary data collection
Non-interventional study

Non-interventional study design

Other

Non-interventional study design, other

Non-PAS, non-interventional, observational, multicentre, one-arm, non-comparative, retrospective study.
Study drug and medical condition

Name of medicine

IMFINZI 50 MG/ML - CONCENTRATE FOR SOLUTION FOR INFUSION

Study drug International non-proprietary name (INN) or common name

DURVALUMAB

Anatomical Therapeutic Chemical (ATC) code

(L01XC28) durvalumab
durvalumab

Medical condition to be studied

Non-small cell lung cancer stage III
Population studied

Short description of the study population

The study population are unresectable stage III non-small cell lung cancer patients treated with durvalumab after chemoradiotherapy. For patients with no prior PD-L1 available, a PD-L1 testing will be done using archived tissue samples from diagnosis, when available.The study is based on the collection of data about the patients treated with Durvalumab after chemoradiotherapy in the real world. The patients participating in this non-interventional study will not receive treatment in relation to the study. Prospective information about treatments will not be collected. The S-REAL study was a Spanish multicentre, observational, retrospective study on patients with unresectable stage III locally advanced non-small cell lung cancer treated in 39 participating centres who were enrolled in an Spanish early access program for durvalumab between 1 September 2017 and 21 December 2018. A total of 251 patients were screened; 244 met the study criteria and were included in data analyses.

Age groups

Adults (18 to < 46 years)
Adults (46 to < 65 years)
Adults (65 to < 75 years)
Adults (75 to < 85 years)
Adults (85 years and over)

Estimated number of subjects

250
Study design details

Study design

The S-REAL study was a Spanish multicentre, observational, retrospective study on patients with unresectable stage III LA-NSCLC treated in 39 participating centres who were enrolled in Spanish early access program for durvalumab (10 mg/kg every 2 weeks) between 1 September 2017 and 21 December 2018

Main study objective

Primary Objective of S-REAL study: To assess effectiveness of durvalumab in patients treated in real-life settings by evaluating PFS defined as time from the index date (date of the first dose of durvalumab received within the Spanish early access program) to the date of investigator-determined disease progression or death (if no progression) or the end of follow-up.

Setting

The heterogeneity of unresectable stage III NSCLC and the diversity of multidisciplinary treatment approaches used in the real-world setting justify the need to collect data from independent cohorts of patients to obtain a more detailed characterization. To achieve this goal, we performed this study to assess the real-world effectiveness and tolerability of durvalumab in a cohort of 244 patients with unresectable stage III NSCLC enrolled in a Spanish early access program. The S-REAL study was a Spanish multicentre, observational, retrospective study on patients with unresectable stage III LA-NSCLC treated in 39 participating centres who were enrolled in an EAP for durvalumab between 1 September 2017 and 21 December2018. A total of 251 patients were screened; 244 met thestudy criteria and were included in data analyses. In April2021, data collected in this study were integrated into the global analyses performed in the international real-world PACIFIC-R study .
The aim of the study was to determine the effectivenessof at least 1 dose of durvalumab in unresectable stage III
LA-NSCLC patients after completion of CRT. In addition, we also aimed to characterize this patient population and the routine management and regimen patterns used to treat their disease. Data were obtained retrospectively and during one routine clinical visit from the electronic medical records of the 39 participating hospitals. The index date was defined as the date on which patients in the EAP received the first dose of durvalumab. Patients were followed from the index date to the end of follow-up.

Outcomes

A total of 244 patients with unresectable stage III NSCLC enrolled in the EAP that received at least one dose of durvalumab after definitive CRT were included for analysis. The median follow-up from the start of durvalumab was 21.9 months [range 1.2–34.7] and only 2 patients (0.8%) were lost to follow-up. Baseline characteristics of patients at the time of EAP inclusion are median age of patients was 67.0 years at the time of EAP inclusion, and 18% were over 75 years. Most patients were men (79.9%), and the majority (97%) were
current or former smokers. At the time of initial NSCLC diagnosis, 47.3% of patients presented nonsquamous histology and 92.7% had stage III disease. The most prevalent comorbidity was hypertension (39.3%), followed by chronic obstructive pulmonary disease (23.8%). From the total of patients tested for EGFR mutational status
(n = 98), 2% had an EGFR-sensitizing mutation. From a total of 176 patients (72.1%) tested for PDL1-
expression, 72.2% presented PD-L1 ≥ 1% (PD-L1 positive patients), 19.9% had PD-L1 < 1%, and 8.0% had
unknown PD-L1 levels. In general, baseline characteristics were similar across both PD-L1 subgroups. One hundred seventy patients (69.7%) had received concurrent CRT (cCRT) and 38 patients (15.6%), sequential CRT (sCRT). The median dose of RT received was 66 Gray (Gy) delivered in a median of 33 fractions.
After CRT, most patients achieved a partial response (76.8%) and 18.6% presented stable disease. Overall, 97.6% of patients with available data had not progressed. All patients had received platinum based regimens of CT. Median time to start of durvalumab after CRT was 72 days. Only 5.6% of patients started treatment within
42 days of CRT completion, and 94.4% were treated outside the 42-day window. Median duration of durvalumab treatment was 10.5 months. Overall, 44.7% of patients completed 12 months of planned durvalumab regimen and received a median of 19 infusions.

Data analysis plan

PFS is calculated from the index date (date of the first dose of durvalumab received within the EAP) to the date of investigator-determined disease progression or death (if no progression) or the end of follow-up for censored patients. PFS S will be estimated and plotted using the Kaplan-Meier method. The median and associated 95% confidence interval will be estimated. The percentage of patients remaining event free at specific timepoints will be displayed: PFS at 12, 18 months. Clinical characteristics, previous and subsequent treatment patterns will be displayed descriptively. -Patients with unknown progression status at the time of data collection will be censored at the date they were last known not to have radiologically and/or clinically progressed. Patients will be followed from the index date (date of the first dose of durvalumab received within the EAP) to the end of follow-up (date of death for patient, withdrawal from study drug, loss to follow-up, or end of study period).

Summary results

A total of 244 patients were followed up for a median of 21.9 months [range 1.2–34.7]. Median duration of durvalumab was 45.5 weeks (11.4 months) [0–145]. Median PFS was 16.7 months (95% CI 12.2–25). No remarkable differences in PFS were observed between patients with programmed cell death-ligand 1 (PD-L1) expression ≥ 1% or < 1% (16.7 versus 15.6 months, respectively). However, PFS was higher in patients who had received prior concurrent CRT (cCRT) versus sequential CRT (sCRT) (20.6 versus 9.4 months). AESIs leading to durvalumab discontinuation were registered in 11.1% of patients.
These results are in line with prior published evidence and confirm the benefits of durvalumab in the treatment
of LA-NSCLC patients in a real-world setting. We also observed a lower incidence of important treatment associated toxicities, such as pneumonitis, compared with the pivotal phase III PACIFIC clinical study.
Documents
Study report

CTO_1Febrero2024 (002).pdf

English (1.08 MB - PDF)View document
Study publications
Clinical and Translational Oncology paper