Systemic Clinical Cancer Treatment (2) Flashcards
What are the primary curative cancers for systemic treatment?
Leukaemia
Lymphomas
Germ cell tumours
What is adjuvant and neoadjuvant chemotherapy?
Improve chances of cure before and after surgery or radiotherapy
What is palliative treatment?
Reduce tumour burden
Symptom control, increase quality of life
Increase survival
What is an objective way to assess the benefit of a therapy?
Volume changes in tumours
What ways can you assess survival to assess the benefit of therapy?
Overall survival
Progression free survival
Relapse free survival
What 3 ways can you assess cancer treatment benefit?
Survival
Objective response
Health related quality of life
How can you use healthy related quality of life to assess cancer treatment benefit?
Objectively assess symptoms, always want a drug which makes the patient as comfortable as possible
What is a complete response?
Disappearance of all target lesions
What is partial response?
A least a 30% decrease in the sum of diameters of target lesions
What is a progressive disease?
At least a 20% increase in the sum of diameters of target lesions
What is stable disease?
Neither sufficient shrinkage to qualify for a partial response nor sufficient increase to qualify for progressive disease
What is objective response rate?
= complete response + partial response
What is disease control rate?
= complete response + partial response + stable disease
How quickly can you determine objective response rate?
In weeks or months of starting treatment
How do you conduct a clinical trial?
Not everyone will get treatment at the same time but they have to have the treatment for the same amount and finish at the same time
What statistical model is used to calculate survival analysis?
Kaplan-Meier
What is the hazard ratio?
It estimates over the period of time of the study the chances of a patient dying of one therapy compared to the other
How is health related quality of life measured?
Patients reported outcomes
Objectively measuring symptom improvement and its impact
Takes into account the toxicities of the treatment
What is primary or inherent resistance?
No response seen, tumour continues to grow and spread
What is secondary resistance?
Initial response but then regrowth of the tumour either while the patient is still on the same medicine or after it has stopped
How does circulating free tumour DNA (ctDNA) work?
The tumour leaks DNA out into the blood and you can sequence this and identify copy number changes, gene mutations and abnormalities
What are the benefits of ctDNA
Because it is a blood test it is non-invasive and is repeatable
Able to detect new tumours a lot earlier than CT scans
How many patients with NSCLC develop EGFR resistance?
50%
What 3rd generation drug targets EGFR and EGFR resistance mutations?
Osimertinib
Of 10,000 chemicals in pre-clinical trials, approximately how many make it to clinical trials and how many are approved?
Clinical Trials - 5
Approved - 1
How many patients are involved in phase I clinical trials?
40-50
What is the main reason for phase I clinical trials?
To get a safe dose optimum
Who take part in phase I clinical trials?
Cancer patients who remain fit but have exhausted all other options
What are the outcomes of phase I clinical trials?
If the drug is safe or if it has unacceptable toxicities
The dose is chosen
Anti-cancer efficacy
What two doses do they generate?
Maximal tolerated dose
Biologically effective dose
What is the biologically effective dose based on?
Pharmacokinetics
Pharmacodynamic biomarker
Why is biologically effective dose used sometimes?
Targeted drugs tend to have less side effects than cytotoxic chemotherapies and therefore you use this dose instead of the really high dose
What is pharmacokinetics?
Measure the concentration of the drug in the plasma or tissue
Why are pharmacodynamic biomarkers used?
To make sure the drug is hitting the right target
may involve a biopsy
How many patients are involved in phase II clinical trials?
50-100
What is the main aim for phase II clinical trials?
To access the potential efficacy
Determine which cancer type it targets based on pre-clinical work and phase I results
Confirm safety, side effects and dose
Is the drug more effective than the current standard of care?
How is the potential efficacy measured?
measuring short term changes in tumour volume
How can you analyse changes in tumour volume?
Waterfall plots - compare against the current standard of care
How many patients are involved in phase III clinical trials?
hundreds - thousands
What is the main aim of phase III clinical trials?
To get the survival benefit of the drug by testing:
- overall survival
- progression free survival
- relapse free survival
- symptom control, quality of life
What is phase IV clinical trials?
Licensing for clinical use involving assessment of all trials
Reimbursement approval from some healthcare systems, including the NHS
What do they consider when healthcare systems complete reimbursement approval?
Comparative clinical effectiveness
Comparative cost effectiveness
What is a biomarker?
A parameter that can be objectively measured in a patient or their disease that will provide information regarding a defined biological process or clinical outcome
What types of biomarkers are there?
Screening biomarkers Diagnostic biomarkers Pharamacodynamic biomarkers Predictive biomarkers Prognostic biomarkers
What are the stages of biomarker development?
Discovery -> Qualification -> Validation -> Implementation
What is the qualification component of biomarker development?
Building up evidence that the biomarker does what it is meant to do
What is the validation component of biomarker development?
The technical process of developing the assay which makes the biomarker and make sure it works on all materials e.g. blood and tissue
Why are predictive biomarkers needed?
Clinical effectiveness
Cost effectiveness
