Breakthrough in lung cancer research
Australian and international researchers have announced a potential breakthrough in lung cancer research – linking it to a genetic mutation for which blocking drugs already exist.
Associate Professor Gavin Wright, the director of surgical oncology at St Vincent's Hospital in Melbourne and a member of the Victorian Cooperative Oncology Group, headed the Australian research team.
The implications of this are exciting as one of the drugs has already been successfully tested in mice seeded with human lung cancer cells. Clinical trials using the drugs will start next year to test whether the drugs can be safely and effectively used to treat people.
"I don't think it's hyperbole to say this is probably the biggest finding in lung cancer research to date," Associate Professor Wright said. "This cancer happens in patients for whom we really don't have anything, apart from chemotherapy."
The study involved researchers from Australia, Germany, the US and other countries, who together recruited patients with lung cancer and collected 1,000 tumour samples, which they genetically analysed.
Results indicated that up to 25% of squamous cell carcinomas featured far too many copies of a gene called FGFR1, that plays a role in healing. Professor Wright said the over-expression of the gene caused uncontrolled cell growth.
The discovery may only be relevant to about 10% of all lung cancers, but Professor Wright said lung cancer's high prevalence meant significant numbers of people stood to benefit.
The study has been published in the journal Science Translational Medicine.
Professor Wright has provided the following information in response to frequently asked questions about this research:
Is the new disovery a wonder drug?
No. This important discovery is actually a DNA abnormality in a gene called FGFR1. This abnormality is found in about a quarter of all squamous cell lung cancers. It allows the cancer to grow endlessly and spread to other parts of the body.
This type of abnormality is relatively simple to target with a certain class of drugs. Whilst there are at least two drug compounds that were co-incidentally invented and stored for future use, they are not yet available for treatment, and have not had sufficient human trials for safety and effectiveness.
Is this FGR1 gene abnormality inherited?
No. The DNA abnormality of this gene only occurs in the lung cancer itself. It is not in the person's normal cells and cannot be passed on to children of the person with lung cancer. Additionally lung cancer itself is not hereditary, and there is no requirement for genetic testing of children or siblings.
Will this discovery help all lung cancers?
No. This FGFR1 gene defect appears to only happen in squamous cell lung cancers. We believe it occurs in 20% to 25% of cases of squamous cell cancer. The drugs to be trialled will only help patients whose lung cancers have the specific FGFR1 gene abnormality.
Who gets squamous cell cancers?
Squamous cell lung cancers are most common in former smokers and current smokers. They also occur occasionally in non-smokers. It is not passed on to children of patients with lung cancer.
Are there different gene abnormalities for lung adenocarcinoma?
Yes. Two DNA or gene abnormalities have so far been discovered in the other common type of lung cancer – adenocarcinoma. There is currently treatment available for these abnormalities in mainstream practice and in ongoing clinical research trials.
The most common abnormality is called EGFR mutation, which is treated with erlotinib (Tarceva®) or gefitinib (Irressa®). It is usually in non-smokers and people of East Asian ancestry, and more common in females. It is found in 10% to 15% of adenocarcinomas.
The less common abnormality is called ALK rearrangement, which is treated with crizotinib. It also mainly occurs in non-smokers. It is found in 4% to 5% of adenocarcinomas.
When will the human trials of the drug for FGFR1 abnormality begin?
The earliest human trial will probably commence towards the middle of next year. This will be a "Phase 1" trial, which means that a limited number of people will receive varying doses of the drug to assess cancer shrinkage, look for side effects, and determine the maximum dose tolerated by humans. Only after the best dose is determined can larger trials begin.
Who would be eligible for FGFR1 trials?
Because this would be initially an experimental drug, patients would only be invited into the FGFR1 trials if they have the following:
- Cancer has been proven to be squamous cell lung cancer by a tissue biopsy.
- Testing of their tumour by the St Vincent's Pathology laboratory proves the cancer has the FGFR1 gene abnormality.
- The cancer has already been treated with current best therapy.
- The cancer has been proven by biopsy to have returned (relapsed).
- There has been no response to standard chemotherapy, or the tumour has returned despite previous standard chemotherapy.
Can I go on the trials if I don't live in Melbourne?
Yes. Provided that you are eligible for the trials (see above) and you are willing to travel to Melbourne for all initial assessments and specified follow-up appointments. The trial drug will be a tablet that will be supplied and taken each day at home in between visits. Unfortunately, there is no government financial assistance at the moment for travel specifically for a clinical trial.
What would the various trials involve?
The Phase 1 trial would involve a small number of patients taking our "best guess" of the correct dose. If there are no side effects, a small number of patients will receive a higher dose. This will continue until several patients in one dose group suffer side effects (e.g. skin rash, diarrhoea) that make that dose intolerable. We would then decide that the next lower dose is the correct dose, as long is it actually shrinks the tumour.
The next trial would be a "Phase 2" trial, which uses the correct dose in a larger number of patients. This confirms whether the drug is effective, and double-checks that the side effects are only minor.
The final trial is a "Phase 3" trial, in which patients who have not yet had chemotherapy will randomly receive either the FGFR1 treatment drug or standard chemotherapy. If this trial confirms the new drug is superior to chemotherapy (less side effects and/or more effective), then it will become the standard treatment for squamous cell lung cancers with the FGFR1 gene abnormality.
Why can't my specialist prescribe the drug right now?
The drugs are currently experimental. Their full side effects are unknown. It is unethical to prescribe a drug without first submitting it to proper clinical research trials.
Should I go in the trial if there's no visible tumour after my recent treatment?
No. If your tumour is in remission or undetectable on scans after your recent treatment then no further treatment is recommended. Should your cancer return (relapse) in the future, you might be eligible for one of the trials, provided you meet the other eligibility criteria (see above).
Are there other trials for lung cancer treatment in the meantime?
Yes. The best place to search for a clinical trial that suits your particular lung cancer and situation in Victoria is the Victorian Cancer Trials Link run by Cancer Council Victoria.
Will there be other gene abnormalities identified for lung cancer in the future?
Most likely yes. The technology we have used to make this discovery is still being used to look for other, less common, gene abnormalities. This further research will depend on future research funding and the availability of suitable lung cancer tissue specimens.
Can I have a consultation regarding treatment or research trial options for my squamous cell lung cancer?
Yes. If you have a referral from your general practitioner, you may request a consultation in my consulting rooms by telephoning (03) 9419 2477.
Can I donate money to help with this research?
Yes. Donations can be made to help with this and future related research by contacting St Vincent's Foundation by telephone 03 9288 3365 or email email@example.com. Please specify that you wish your gift to be used for the Clinical Lung Cancer Genome Project.
For more information on cancer, including what it is and common types of cancer, see Cancer: Overview.
Article Date: 12/1/2011
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