KEY POINTS:
Herceptin has attracted huge international attention since a leading medical journal suggested the drug might even be "a cure" for breast cancer.
As New Zealand still debates whether to extend funding of the medicine, an even newer one, lapatinib, is predicted to surpass it, in effectiveness and in
cost.
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Lapatinib (brand name Tykerb) is still an experimental drug. Its maker, GlaxoSmithKline, filed an application in September for it to be licensed in the United States on the strength of its performance in a large, advanced trial.
Using it with the chemotherapy drug Xeloda stopped the cancer's growth for 36.9 weeks, nearly double the time for chemotherapy alone. The trial was among women with advanced cancer whose disease had progressed after treatment with Herceptin and other therapies.
Auckland City Hospital cancer specialist Associate Professor Vernon Harvey hopes some New Zealand patients will be involved in future lapatinib trials, as they were with Herceptin.
A number of trials were starting in the next six to 12 months around the world, he said.
"We would certainly hope to contribute to some of those."
Breast cancer is New Zealand's most common female cancer. The recorded rate is rising, which is thought to be the result of the introduction of breast screening in 1998, although the death rate is declining.
Treatment usually involves some combination of surgery, radiotherapy and drugs. The mix depends on factors such as the stage of the cancer, how aggressive and what type it is and whether the patient has reached menopause.
In the cancer research world where small advances are happening daily, Herceptin has been a genuine breakthrough - a relatively new kind of drug that is dramatically more effective against one of the West's big killers, even though the type of disease it can help is only a quarter of breast-cancer cases.
It become widely known after Dr Gabriel N. Hortobagyi, of the Texas University breast oncology department, said after four large Herceptin trials: "The results are simply stunning."
Writing in the New England Journal of Medicine last year, Dr Hortobagyi said that Herceptin "may even be a cure".
The US National Cancer Institute viewed Herceptin as "a major turning point".
But in New Zealand, the drug is controversially not state-funded for women with early breast cancer, as it is considered too costly for the benefits shown - although it is funded if the cancer has spread. Some women with early disease are paying around $100,000 for the year-long course.
Results from one trial showed that adding Herceptin after chemotherapy increased disease-free survival to 80.6 per cent of patients, 6 percentage points better than the group without it. Overall survival was 92.4 per cent, 2.7 points better with Herceptin than without.
The differences may not look dramatic, because more than three-quarters of all the patients had survived without disease. But assessed statistically, the relative risk of death was 26 per cent lower for the Herceptin patients - and that's what has made activists out of breast cancer patients and their loved ones.
Herceptin is one of a new class of anti-cancer drugs. It binds to a finger-like receptor called HER2, found on some cancer cells. In this way the drug blocks a protein which would otherwise aid tumour growth.
About a quarter of breast cancers are HER2 positive, meaning they express large quantities of the HER2 receptor. This is an aggressive form of the disease, which responds poorly to some chemotherapy and is often associated with shorter survival times.
Herceptin is a targeted therapy, aiming at a certain cancer-signalling pathway. Targeted therapies often cause fewer serious side-effects than chemotherapies, although Herceptin is linked to heart problems in some patients.
Another promising experimental approach to breast cancer is emerging from studies at the Liggins Institute in Auckland of breast cancer cell growth hormones and proteins called trefoil factors (TFF).
"TFF both stops cancer cells dying and ... also promotes their invasion and metastasis," said Professor Peter Lobie, of the Liggins Institute and Neuren Pharmaceuticals.
"We showed that taking TFFs out from cancers produced death of the cells by a natural process ... without any apparent side-effects in pre-clinical trials."
Growth of breast cancers and other common tumours has been reduced in laboratory experiments using antibody fragments directed against TFF proteins. Neuren is developing anti-cancer therapies based on its discoveries and, like Herceptin, using targeted human antibodies.
Survival tends on average to be better in breast cancer than with many other cancers.
Dr Harvey said that with standard chemotherapy, 70 to 80 per cent of patients whose primary cancer had spread no further than a lymph node were expected to be alive and disease- free 10 years later.
Newer chemotherapy drugs called taxanes could add 5 percentage points and hormone blocking therapy - used against cancers which can be helped to grow by the female sex hormones oestrogen and progesterone - 10 more.
Newer hormonal drugs called aromatase inhibitors, including Arimidex and Femara, are steadily replacing tamoxifen, long the mainstay of hormone therapy. They can significantly reduce the risk of cancer coming back or spreading.
At the molecular level, lapatinib, like Herceptin, targets the HER2 receptor - and also a second cancer cell signalling pathway. While Herceptin works at the cancer cell's surface, lapatinib can get inside because of its smaller structure.
Another possible benefit is that, unlike Herceptin, lapatinib can enter the brain, so it might stop the higher incidence of cancer relapse in the brain associated with Herceptin.
The definitive causes of breast cancer remain unclear, but about 5 per cent of cases are related to inherited gene mutations. The best known are the BCRA 1 and 2 gene. When they are faulty, this prevents repair of other genetic faults which lead to cancer.
British researchers have started a trial in Europe, the US and Australia to establish the best chemotherapy for women with advanced breast cancer and a fault in BRCA 1 or 2.
In the lab, carboplatin was up to 20 times more effective than standard chemotherapy at destroying cancerous cells with the faulty genes.
Many areas of cancer research apply to various types of cancer. Drugs like Avastin, to prevent tumours extending their blood supply, are a major area of study and Avastin, despite some serious side-effects, has proved beneficial in breast cancer trials.
Dr Harvey said a number of these anti-blood-supply drugs were lining up to be tested.
"We are negotiating through the Australia New Zealand breast cancer study group to try to get access to at least one of those."
A development overseas is to try people on several expensive targeted therapies, a trend which holds hope for patients but alarms health-funders.
Wonder drug helps to block tumour cell growth
Immunotherapy uses the body's immune system to fight cancer or to lessen the side effects of some treatments.
Agents known as biological response modifiers alter the interaction between the body's immune defences and cancer cells to boost, direct, or restore the body's ability to fight the disease.
One form of immunotherapy is the use of monoclonal antibodies - proteins that have been created in the laboratory from a single type of cell. Each is designed to be effective against a particular cancer.
The antibodies locate and bind to cancer cells. Some work by triggering the body's natural immune response to attack cancer cells, while others are programmed to interfere with the cancer's growth.
The best known of monoclonal antibody therapies is Herceptin.
Herceptin works by blocking tumour cell growth. It binds to the HER2 growth receptor on the tumour cell surface, and stops the receptor from signalling for the cell to grow and divide. Immune system cells known as natural killer (NK) cells also attach to the monoclonal antibody when it is bound to the tumour cells. The NK cells then detect an abnormality, and kill the tumour cell.
Monoclonal antibodies can be used alone or to carry drugs, radioisotopes and toxins directly to the tumour.
Clinical trials are under way for cancers ranging from leukaemia to brain tumours.
- additional reporting: Errol Kiong
