UpSwinG: Real World study on TKI activity in Uncommon mutations and Sequencing Giotrif®

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation

  Effectiveness study (incl. comparative)

  Other
• If ‘other’, further details on the scope of the study:
  The study observes how long patients with non-small cell lung cancer (NSCLC) benefit from treatment with Epidermal Growth Factor Tyrosine Kinase Inhibitor (EGFR-TKI).
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  Non-interventional, multi-country, multi-centre study based on existing data from medical records or electronic health records

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (L01XE13) afatinib

  afatinib

  (L01XE02) gefitinib

  gefitinib

  (L01XE03) erlotinib

  erlotinib

  (L01XE35) osimertinib

  osimertinib
• Medical condition to be studied:
  Non-small cell lung cancer

Population studied

• Short description of the study population:
  Patients with non-small-cell lung cancer (NSCLC)
• 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:
  400

Study design details

• Study design:
  Non-interventional, multi-country, multi-centre study based on existing data from medical records or electronic health records.
• Main study objective:
  The study aims to describe the time on treatment until its end or death.
• Setting:
  A total of 56 study centers in 9 countries (Austria, France, Germany, Italy, Spain, United Kingdom, Japan, Korea Republic, and Taiwan Republic of China) were initiated in this non-interventional study.
• Outcomes:
  Time on treatment with EGFR-TKI(s), Overall survival, ORR, methodology and material used for mutational testing. Uncommon cohort only: time on treatment until failure of second line (TTF2).
• Data analysis plan:
  The two cohorts will be analysed separately- Uncommon mutations- Sequencing of osimertinib after afatinibThe primary endpoint for both cohorts is time on treatment. Kaplan-Meier estimates will be calculated. ; ; In addition, the median will be tabulated along with the two-sided 95% confidence interval, using Greenwood’s variance estimate. ; The primary analysis will be repeated within subgroups. ; The following additional endpoints will be analyzed similarly to the primary endpoint.- overall survival- time on treatment until failure of second-line (uncommon cohort only)Patients who were not known to have discontinued treatment will be censored on the date they were last verified to have been on treatment.; As an additional exploratory analysis, the data from the sequencing cohort of this study may be pooled with the previous GioTag study.
• Summary results:
  Uncommon mutation cohort ; Afatinib is the standard of care (SoC) for most patients with uncommon mutations. The study supports the use of afatinib against major uncommon and compound EGFR mutations with additional broad activity against other uncommon EGFR mutations and some exon 20 insertions. It provides insights into treatment and testing strategies and emphasizes the need for broad testing and a clear description of mutations given their ; heterogeneity. ; ; Sequencing cohort ; The main study findings were in line with the expectations and well aligned to those obtained rom the GioTag study, which can now be enriched with the Upswing data (obtained from a cohort composed especially of Asian patients). Therefore, the Upswing study allowed to further investigate the overall benefit for the sequential EGFR TKI treatment with afatinib and osimertinib for the common EGFR mutations. ; ; The ADRs to Giotrif® reported in this study, and their severity were consistent with the known safety profile of afatinib (Giotrif®). There were no new safety observations or concerns identified in this study. ; ; These findings complement the body of evidence in the real world for a better evidence-based therapy decision in NSCLC advanced EGFR mutated setting.