When cancer is described as “advanced,” that means it has started to spread. Today, progress in understanding the origins of cancer and the development of new medications have improved patients' odds of living with and beyond advanced cancers.
Lung cancer is a perfect example of how medication advances are helping survivors live longer without the disease getting worse.
In the past three months, two medications have been approved to treat advanced non-small cell lung cancer (NSCLC) — the most common form of lung cancer in the US that will be diagnosed in about 228,000 Americans this year.
In May, the US Food and Drug Administration (FDA) approved the extended use of Tarceva (erlotinib) as a first-line (initial) therapy for advanced NSCLC. This medication is also used as a second-line therapy for lung cancer patients who had first been treated with chemotherapy.
Then in mid-July, the FDA approved Gilotrif (afatinib) as a first-line therapy for NSCLC.
Both of these medications are taken by mouth and are members of a class of medications called tyrosine kinase inhibitors (TKI).
Tarceva and Gilotrif are both used to treat advanced lung cancers that have specific epidermal growth factor receptor (EGFR) gene mutations. These genetic defects are seen in about 10 percent of lung cancers in Western countries and in 40 to 50 percent of lung cancers in Asia.
Along with these medications, the FDA approved two tests, which scientists call assays, that analyze NSCLC tumors for EGFR mutations.
The companion test for Tarceva is called the cobas EGFR test. The Gilotrif assay is known as therascreen EGFR RGQ PCR Kit.
Being able to identify genetic mutations that are fueling a cancer is the very essence of personalized medicine. Molecular testing allows physicians to develop treatment plans that target the individual’s specific disease drivers.
Advancing personalized cancer treatment
dailyRx News spoke with leading lung cancer expert Fred R. Hirsch, MD, PhD, professor of medicine and pathology at the University of Colorado Cancer Center, about these two new medications.
The approval of these medications "...is an important step towards personalized therapy of patients with lung cancer," said Dr. Hirsch.
"It has been clearly demonstrated in several large randomized studies that EGFR tyrosine kinase inhibitors give significant improvement of progression-free survival [time during which cancer doesn’t get worse] compared to traditional chemotherapy in this specific subgroup of patients," Dr. Hirsch explained.
Patients treated with Tarceva had a median progression-free survival of 10.2 months, compared to 5.2 months for patients given chemotherapy.
People treated with Gilotrif had a 4.2-month longer progression-free survival than did patients treated with chemotherapy.
The median (middle) progression-free survival for patients treated with Gilotrif was 11.1 months, compared to 6.9 months for patients receiving chemotherapy.
Neither medication has an impact on overall survival, and Dr. Hirsch explained why.
"The reason for not demonstrated overall survival benefit in the studies is simply related to study trial designs, which have allowed cross-over therapy [switching to another therapy] after progression in one of the study arms, which of course dilutes the real effect of the first given therapy," he said.
We asked him about the major differences between Tarceva and Gilotrif. Dr. Hirsch said that Gilotrif targets and attacks more genetic mutations than Tarceva.
One of the mutations Gilotrif strikes is one that can occur during treatment and which keeps that treatment from working.
Identifying the specific genetic mutations that a lung cancer patient has is crucial before treatment begins, Dr. Hirsch said.
"If this treatment is not given to this subpopulation as first line treatment, there is a high risk (about 30 percent) that the patient never will receive this active agent. This is because, unfortunately, many patients (about 30 percent) with advanced NSCLC will never receive second-line therapy, and they will never get the chance to receive Tarceva or Gilotrif, both of which are highly effective in this particular subpopulation of patients with tumors harboring EGFR mutations," he said.
Advancing genetic testing
Dr. Hirsch said that the approval of the companion tests that identify EGFR mutations is also critically important.
"Along with the drug approvals, the FDA also approved strictly validated [results can be confirmed] test/assays for determining EGFR mutations, which now needs to be implemented widely in clinical practice," Dr. Hirsch said.
"For facilitating the implementation of molecular testing of tumors from patients with advanced NSCLC," Dr. Hirsch continued, "the International Association for the Study of Lung Cancer (IASLC), College of American Pathologists (CAP) and Association for Molecular Pathology (AMP) have just jointly recently published guidelines for molecular testing, who should be tested, how they should be tested and how to report results."
Dr. Hirsch said that in addition to keeping the disease from getting worse, these medications help patients feel better by improving lung cancer symptoms such as cough and shortness of breath.
"A few more months of progression-free survival can mean a lot for the patients, particularly when it also goes with symptomatic improvement," Dr. Hirsch said.
Tarceva costs roughly $6,200 for 30 tablets. The wholesale acquisition price before retail mark-up for a month's supply of Gilotrif is $5,500.
When asked what these approvals mean for patients, Dr. Hirsch said, "With approval of afatinib [Gilotrif], there is another option for treatment of EGFR mutation positive tumor patients. Whether it is more effective than erlotinib [Tarceva] is on this stage not clear. Ongoing studies will show."