A new class of drugs offers hope to lung cancer patients who have a specific mutation in their tumour cells.
LG LAU was in her mid-thirties when she was first diagnosed with lung cancer. She had caught a “normal” cold, and her early symptoms included persistent coughing, shortness of breath, loss of weight and a hoarse voice.
When her cough worsened and wouldn’t go away for several weeks, she went to see a doctor, who diagnosed her condition as tuberculosis.
After taking the prescribed medication for about two weeks, there was no improvement in her condition.
A Filipino girl watches as a male
smoker walks by with a lighted cigarette. Asian female non-smokers who develop
lung cancer are more likely to have a mutation that is sensitive to treatment by
EGRF-TKI drugs. In fact, her health gradually worsened, and by the end of the third week, she had difficulty eating and started losing weight.
By the end of the month, she became too weak to move around on her own and had to get about in a wheelchair.
Her husband finally couldn’t bear to watch her suffer any longer, and in spite of her protests, brought her to see a specialist, who ordered a chest X-ray and CT scan.
The results were conclusive; although she had never smoked in her life, she was diagnosed with Stage 3B non-small cell lung cancer (NSCLC).
Her doctor insisted that she go for a follow-up biopsy to determine if she was EGFR (epidermal growth factor receptor) mutation positive. EGFR is a cell membrane receptor found on tumour cells, which shows increased activity in cancer cases.
The results came back positive, so her doctor put her on drugs that inhibit EGFR (called EGFR-specific tyrosine kinase inhibitors, or EGFR-TKI) for a month as part of her first-line treatment.
The results were remarkable; when she came back after a month for her follow-up, Lau’s symptoms were gone.
She had regained most of her lost weight, and was able to speak clearly as she no longer suffered from a hoarse voice.
She had even regained enough strength to walk into the clinic on her own!
A follow-up CT scan showed significant regression in her cancer.
She stayed on EGFR-TKIs for two years after the biopsy. As she only had to take one pill a day, Lau was able to carry out her daily activities with minimal disruption.
She was able to continue working while she completed her treatment course, and today, remains tumour-free and has a beautiful little girl.
Not just smokers
Dr Chong... The ideal aspects to look
out for in personalised medicine are effectiveness, minimal or no side effects,
conveniences and affordability. With the advent of personalised medicine, we
have managed to fulfil the first three criteria. Lau’s battle with lung cancer is not uncommon by today’s standards.
Lung cancer is often mistaken as a “smokers-only” disease that affects mainly the male population.
According to her obituary in The Telegraph, actor Kathryn Joosten, who died earlier this month of the disease, once said that lung cancer “is far more lethal, and a bigger killer of women than all the other cancers combined”.
As such, most stories seldom have such a happy ending. Hardly surprising, as lung cancer is ranked as the number one killer cancer in Malaysia, and also, worldwide.
While it is true that a large percentage of lung cancer patients are smokers, the number of non-smokers who fall victim to the disease is rising substantially.
The 2006 National Health and Morbidity Survey (NHMS) showed that the number of non-smokers afflicted with lung cancer had increased to almost 15% of the total number of lung cancer cases in Malaysia, compared to only 10% in the previous NHMS.
Unfortunately, as Joosten also said, lung cancer has a stigma because of the relationship to smoking — “you did it to yourself” — and therefore, the belief that somehow it is something to be ashamed of.
But despite the grim prognosis, it is critical that patients diagnosed with lung cancer do not give up hope, and most importantly, the opportunity to live life to the fullest.
The development of tyrosine kinase inhibitors targeting the EGFR in the past couple of decades has brought the promise of longer survival rates for patients with NSCLC.
Targeting a mutation
Lung cancer can be divided into two major types; one of it, NSCLC accounts for 85-90% of all cases.
“Data from recent studies like the Iressa Pan-Asia Study (IPASS), and other supporting phase II and phase III trials have emphasised that you really need to send the biopsy specimens from patients with NSCLC for EGFR gene mutational analysis before deciding on treatment, as is done in breast cancer,” says Prof Dr Liam Chong Kin, a professor of medicine at the Division of Respiratory Medicine, Department of Medicine, University Malaya Medical Centre (UMMC).
The idea behind targeting the EGFR is to block the growth signal initiated by it. One of the components in the receptor involved in signal transmission is the tyrosine kinase enzyme.
Prof Liam is quick to add that patients with EGFR-mutated tumours are the “more fortunate” patients. Having an EGFR mutation means that patients have the option to skip the rigours of chemotherapy and opt for the newer oral drug treatment. They are also more likely to survive longer and enjoy a better quality of life.
With the EGFR-TKIs, the natural history of EGFR-mutated tumours is being changed as these drugs allow for personalised medicine. This is a form of medicine that uses information about a person’s genes, proteins and environment to prevent, diagnose and treat disease.
“This strategy has more benefits than chemotherapy, and the focus of personalised medicine is on improving the quality of life of these patients as much as possible, thus enabling them to lead normal and fulfilling lives, just like Ms Lau’s,” he explains.
The IPASS also confirms the benefit of the EGFR-TKI called gefitinib, as the front-line therapy in patients with EGFR-mutated tumours.
It was also discovered that the EGFR mutation is present in tumours from over 40% of patients with the non-small cell type of lung cancers.
Out of this group, the incidence of EGFR mutation was higher among those who had never smoked before, compared to those who have smoked. EGFR mutation was generally highest among the adenocarcinoma subtype of NSCLC.
A PET scan showing the presence of
tumours in the lung and a nearby lymph node. Go for the test!
Both Prof Liam and Dr Chong Kwang Jeat, an oncologist at the Radiotherapy & Oncology Department in Mahkota Medical Centre, Malacca, agree that regardless of their phenotype, lung cancer patients should find out whether or not their tumours are EGFR-mutation positive, as this is very common among the Asian population.
Prof Liam says: “Physicians now know that they need to screen their patients for EGFR mutations, and if mutations are detected, patients should be started on a TKI, such as gefitinib, depending on the standard of care at each institution.
“Generally, around 30%-40% of NSCLC patients are EGFR-mutation positive.”
He adds: “The trend for never-smokers to develop lung cancer is also increasing, and among this group, easily 60% of them have lung cancers that are EGFR-mutation positive.
“Patients with EGFR-mutation positive lung cancer frequently enjoy significantly longer cancer progression-free periods when treated with EGFR-TKI drugs.”
According to Prof Liam, EGFR-TKI drugs have been proven to halt the progression of the cancer, as well as cause significant cancer shrinkage in patients who respond very well to treatment.
“In many cases, the patients were able to lead reasonably normal lives without having to suffer the usual side-effects brought about by cytotoxic chemotherapy.”
Dr Chong says that a patient’s characteristics allows them to guess with some accuracy whether they are likely to be EGFR-mutation positive or not.
Prof Liam... Lung cancer patients with
EGFRmutated tumours are more fortunate as they have the option of taking oral
medication, as well as have a better prognosis, compared to other lung cancer
patients. “An Asian never-smoker with adenocarcinoma has a 60-70% chance of being EGFR-mutation positive, while an Asian with adencarcinoma, who was a light smoker and has quit smoking, has about a 47% chance of being EGFR-mutation positive.
“Even a current smoker with adenocarcinoma has up to a 30% probability of harbouring the EGFR mutation.
“Hence, the only sure way of finding out is to actually do the EGFR-mutation test on all adenocarcinoma patients, as we aim to use an EGFR-TKI as the first-line treatment for all patients. If they are EGFR-mutation negative, then chemotherapy would be indicated.”
He explains that although EGFR-mutation positive patients also respond well to chemotherapy, he prefers the oral drug as it is more effective, has fewer side effects, and is extremely convenient — patients need only take one tablet a day at home, compared to frequent intravenous injections of chemotherapy at the hospital.
“All these factors combined would tremendously improve the quality of a patient’s life, which is one of the most important goals of any cancer treatment!” he says.
Targeted therapy
Dr Chong explains: “Personalised medicine is to customise a treatment to suit an individual patient. We know cancer is a heterogenous disease and a one-size-fits-all treatment cannot be an ideal approach.
“Imagine if an ineffective treatment is given to a patient, and he or she suffers the adverse effects without any improvement in the disease. This is a double whammy!
“In fact, not only is this a waste of resources, one might also squander the opportunity to control the cancer.”
He says: “Previously, the mainstay of treatment was standard cytotoxic chemotherapy, but with the advent of personalised medicine, we can now use the right drug for the right patient at the right time.
“As we are able to identify the right patient for the right drug, we can now tailor the drug for the patient.
“In fact, nowadays, even standard cytotoxic chemotherapy is slowly evolving to become more personalised.”
However, most importantly, Dr Chong adds: “Where previously lung cancer patients only had chemotherapy to choose, and often suffered unnecessarily due to the blunderbuss approach of chemotherapy, now they have an option of taking approved first-line treatments that contain EGFR-TKIs to address their cancer without killing healthy cells as well.”
Both doctors were concerned that while most healthcare professionals who specialise in cancer are aware of EGFR mutation and the approved first-line treatments available, there are still many non-cancer specialists who are not.
Hence, the reason why a lot of effort is being put into educating the public and healthcare professionals on the topic, via public service announcements and continuing medical education (CME) programmes throughout the nation.
Regardless of whether the patient fits the description of a typical EGFR-mutation positive candidate or not, getting tested for EGFR mutation is very important. Giving up the fight now means abandoning any chances for recovery.
http://thestar.com.my/health/story.asp?file=/2012/6/24/health/11502622&sec=health
