Pierre Fabre ambispective non-small cell lung cancer OCTOPUS study

• Research type

  Research Study

• Full title

  An ambispective observational study describing diagnosis and treatment patterns in adults with metastatic non-small cell lung cancer with BRAF V600E mutation in clinical practice, to assess treatment effectiveness and quality of life.

• IRAS ID

  310116

• Contact name

  Jason Adhikaree

• Contact email

  jason.adhikaree@nuh.nhs.uk

• Sponsor organisation

  Pierre Fabre SA (PFSA)

• Duration of Study in the UK

  2 years, 10 months, 1 days

• Research summary

  Research Summary

  This is a non-interventional study with the goal to describe treatment patterns for metastatic Non-Small Cell Lung Cancer(mNSCLC).

  Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 80% to 85% of all lung cancer diagnoses. Approximately 40% of newly diagnosed NSCLC patients have stage IV disease. The 5-year survival rate for patients diagnosed with NSCLC is 24%. Approximately 1% to 8% of patients with NSCLC harbour a BRAF-mutation. The most common BRAF mutation, the V600E, is observed in 1-2% of lung adenocarcinomas.

  This study will describe the treatment patterns in clinical practice in adult patients with mNSCLC with a BRAF V600E mutation (specific gene mutation) and assess Real-World Progression-Free Survival (rwPFS) and Overall Survival (OS) as well as safety of each treatment.

  Summary of Results

  This was an observational study. This means doctors observed what happened as part of normal care, without changing or influencing treatment choices. People followed their usual care. No extra tests or visits were required for the study.
  The main objective of this study was to describe how doctors usually treat adults living with metastatic Non-Small Cell Lung Cancer (NSCLC) with a BRAFV600E mutation. In particular, the study looked at the treatments received after diagnosis of the metastatic disease and the treatments given in case of progression of the disease or in case of low tolerability.
  This study took place in France, Germany, Italy, Spain and the United Kingdom.
  The researchers did not assign or require any specific or experimental treatment. Doctors chose the most appropriate treatment as part of usual medical practice. The study collected information from medical records in hospitals about the chosen treatment and about what happened after the treatment initiation.
  Due to local regulation in Italy, people who died before the study started, could not be included in the analysis. As a result, only people who were still alive when the study began were included. This may have made the treatments appear more effective than they actually were, because the analysis included only people who had survived long enough to be part of the study.
  To better understand the results, additional analysis were carried out without including participants from Italy.

  A total of 206 people participated in the study, and 184 were included in the main analysis. An additional analysis was conducted excluding participants from Italy. In this analysis, 134 of the 152 non-Italian participants were included.
  At initial diagnosis, participants’ average age was 68 years old.

  Adverse events results:
  Participants can have unwanted health issues while receiving treatment during the study. These health issues may or may not be caused by the treatments. They are called adverse events.
  Adverse events are described below in the overall people as well as in people excluding those from Italy.

  Participants
  Total
  (out of 184 participants) Total
  (out of 134 participants)
  Without participants included in Italy
  Participants who had adverse events 99 (54%) 67 (50%)
  Participants who had serious* adverse events 58 (32%) 47 (35%)
  Participants who had at least one adverse event of special interest 91 (50%) 61 (46%)
  = participants
  * An adverse event is serious when:
  - It results in death,
  - It puts life in danger,
  - It results in hospitalisation or prolongs it,
  - It causes lasting problems,
  - It results in health problems in babies or foetus, or,
  - It is considered medically important.

  99/184 (54%) participants had at least one adverse event, 58 (32%) had at least one serious* adverse event. Of the patients with at least one serious adverse event, 29% died.
  91 (50%) had at least one adverse event of special interest, which are events that lead to switching to a different treatment, changing the dose of the treatment, stopping the treatment permanently or temporarily, hospitalisation or prolongation of hospitalisation.

  The table below shows the most frequent adverse events reported in at least 6 patients (≥ 3%) of the total participants.

  Adverse event Total
  (out of 184 participants)
  Fever 17 (9%)
  Fatigue 16 (9%)
  Nausea 16 (9%)
  Diarrhoea 13 (7%)
  Shortness of breath 11 (6%)
  Low level of white blood cells 11 (6%)
  Itchy skin 10 (5%)
  Decreased appetite 9 (5%)
  Oedema peripheral 9 (5%)
  General physical health deterioration 8 (4%)
  Joint pain 7 (4%)
  Vomiting 7 (4%)
  Anaemia 6 (3%)
  Constipation 6 (3%)
  Rash 6 (3%)
  Urinary tract infection 6 (3%)
  = participants

  BRAF mutation test
  To check for specific genetic changes, tests were done using two methods, in the 184 participants:
  • Next Generation Sequencing: used in 61% of cases, this method reads large amounts of DNA quickly to find genetic changes.
  • Polymerase Chain Reaction: used in 30% of cases, this method copies small amounts of DNA to make them easier to study.
  The average time from NSCLC diagnosis to BRAFV600E testing was around 1.5 months.

  Participants characteristics at initial diagnosis of the metastatic NSCLC
  99/184 participants (54%) were male.
  124/173 participants (72%) were previous or current smokers.
  Comorbidities were reported for 124 participants. Comorbidity refers to the simultaneous presence of two or more medical conditions in a participant. The most frequent comorbidities were high arterial blood pressure (39%), diabetes (16%) and heart disease (13%).
  Most participants (86%) had metastatic disease (stage IV) at initial diagnosis.
  At initial diagnosis, 58% of participants had visceral metastases, 67% had non-visceral metastases, and 20% had brain metastases.
  Most of the participants had an ECOG* of 0 (fully active) or 1 (restricted in physical activity) at first line treatments (80%) and at second line treatments (64%).
  * ECOG (Eastern Cooperative Oncology Group) is a performance status.

  Treatment of patients
  When excluding the participants from Italy, all (100%) the participants received first line treatments and 73/134 (54%) received second line treatments.
  For both first- and second-lines treatments, the most common therapy was dabrafenib + trametinib combination therapy* with 37% of participants receiving this therapy in first line and 52% in second line.
  * Dabrafenib and trametinib are marketed drugs, and both of which are targeted therapies. Targeted therapy is a drug treatment that inhibits specific targets such as BRAF proteins to stop cancer cells from growing and spreading (oral treatment).
  The table below shows the treatments participants received.

  Treatments First line treatment
  Total
  (out of 134 participants) Second line treatment
  Total
  (out of 73 participants)
  Dabrafenib + trametinib combination therapy 50 (37%) 38 (52%)
  Chemotherapy alone 27 (20%) 11 (15%)
  Pembrolizumab + chemotherapy 24 (18%) 8 (11%)
  Pembrolizumab alone 13 (10%) 2 (3%)
  Other treatments 20 (15%) 14 (19%)
  = participants

  Overall survival
  Overall survival refers to how long a person lives after starting their first line treatments for NSCLC, regardless of the cause of death.
  When excluding the participants from Italy, the median* overall survival time was 20 months.
  When excluding the participants from Italy, after dabrafenib + trametinib as first line treatment, the median overall survival time was 24 months.
  When excluding the participants from Italy, after dabrafenib + trametinib as second line treatment, the median overall survival time was 28 months.
  * The median is the middle value when results are placed in order. Half of the results are at or below the median, and half are at or above it.

• REC name

  London - Central Research Ethics Committee

• REC reference

  22/PR/0725

• Date of REC Opinion

  29 Jul 2022

• REC opinion

  Favourable Opinion