Spanish Real World Data on unresectable stage III NSCLC patients treated with durvalumab after chemoradiotherapy (S-REAL Study)

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
• 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:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 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.