Patients who live for many years following a cancer diagnosis will likely require additional support, and a whole new kind of follow-up care.
by John Otrompke
Dramatic developments in studies of patients with advanced cancer suggest that the day may be coming within our lifetime when most cancer patients will experience the disease as a chronic illness, if evidence from this year’s annual meeting of the American Society for Clinical Oncology (ASCO) is any indication.
While the day may arrive universally by the year 2020, for those with some forms of the disease, it may already be here, scientists said.
Gastrointestinal stromal tumor (GIST) is a case in point. “GIST was a solid tumor which nothing had ever shrunk,” said George D. Demetri, MD, senior vice president for experimental therapeutics at the Dana-Farber Cancer Institute in Boston. “Once it spread, people would die uniformly within six months.”
Demetri and colleagues treated the first patient with GIST with Gleevec, which had been invented by scientists at the Oregon Health and Science University and already approved for chronic myeloid leukemia.
Within weeks, the tumor shrank for the first time, Demetri said. “Now, people have at least five years of life to look forward to. There are even about 15 percent of our first patients from 2000 who are still alive,” he added.
Gleevec was approved for the treatment of GIST in 2002. Unfortunately, however, most of the patients developed resistance to Gleevec, and many ultimately succumbed. “We found that one out of ten million cells have two cancer mutations; those are the seeds of resistance, and under the selection pressure of Gleevec, they grow,” Demetri explained.
Then, scientists invented another drug that would inhibit the enzyme driver of GIST—Sunitinib, which was approved in 2006. “Then we found tertiary, and quaternary resistance mutations,” he said. “Now, the median time to progression on Gleevec is five months. So why are patients living for five years? Because we have turned this disease into a chronic illness,” explained Demetri, who presented results this year from a phase III study of Regorafenib, a new, experimental targeted therapy for GIST. Regorafenib increased the median progression-free survival in patients with advanced GIST, who had already failed two other therapies, by almost five months, versus less than a month with placebo, according to the abstract.
Is PFS the Key to Overall Survival?
Demetri’s results may be typical of what scientists can expect to see from future meetings of ASCO. One month of progression-free survival is equivalent to 1.3 months of overall survival, according to a meta-analysis of 124 clinical trials involving more than 40,000 patients. The data were discussed in a poster presented at the meeting by Evadne Turner, PhD, a senior health economics associate with Boehringer Ingelheim, in Australia.
“Since there are now 12 million cancer survivors in the U.S., we can calculate that a million cancer deaths have been avoided since the 1990s,” said Michael P. Link, MD, professor of pediatric hematology/oncology at Stanford University School of Medicine, and immediate past-president of ASCO.
While many of these cases have been cured outright, and many more cases of cancer can expect to be prevented in the future with vaccines and proper public health measures, maintenance of chronic patients is likely to be an important part of the future, Link said.
“We have to understand what starts the cancer, and what keeps it going. Is there a way of throwing a wrench in the machinery? We might have to continue to give them medicine to make sure the machinery doesn’t start up again,” he explained.
While drugs like Gleevec revolutionized treatment for CML, other drugs are being discovered today which will likely do the same thing for other forms of cancer.
“There is a relatively new drug called Crizotinib, which was first discovered for use in children with lymphoma. However, the drug, which targets an enzyme called ALK, has also been successful in treating patients with advanced lung cancer,” Link said. “Only about 5 percent of lung cancers are driven by ALK, but if you give it to these patients, they have an unbelievably dramatic response. It doesn’t last very long, but it turns out this ALK is important in breast cancer, and a couple of childhood cancers as well,” he added, noting that Crizotinib was approved last year for the treatment of lung cancer.
New research regarding Crizotinib was presented at this year’s ASCO meeting by Dr. Yael Mossé, MD, Link said.
Somewhere, Another Giant is Falling
Some of the deadliest forms of advanced cancer were put on trial at this year’s ASCO conference. Another good case in point was metastatic melanoma, which once spelled death for its victims within a matter of weeks. But this year, studies were presented concerning a number of drugs, such as Dabrafenib and Vemurafenib, that showed effectiveness against melanoma, even in its advanced forms.
“There was enormous excitement at ASCO this year. The melanoma session, which used to be quite poorly attended, was held in one of the big auditoriums, and it was packed with thousands of people,” said John Thompson, MD, professor of melanoma and surgical oncology at the University of Sydney.
“The incidence of melanoma continues to rise, and there were no major advances in treatment for the last 50 years, until some of the targeted therapies became available. People with extensive disease now get complete remissions, but we’re only prolonging life by a few months, not getting a curative result,” explained Thompson, who took part in a case study at the ASCO conference.
“To have something that actually works is a dramatic change,” Thompson added, noting that his institution currently has over 200 patients enrolled in 15 to 20 clinical trials with the new drugs.
Another case in point is Afatinib, an experimental agent under study by Boehringer Ingelheim. The drug showed better results in patients with advanced lung adenocarcinoma, even when compared with the current frontline therapy, pemetrexed/cisplatin.
In the study of 345 patients with advanced cancer, those patients in the cisplatin arm had a median progression-free survival time of 6.9 months, compared to 13.6 months for those patients on the experimental medication, according to the abstract.
“The patients all had a mutation for the EGFR protein, which is predominantly seen in Asian lung cancer patients,” said Dr. James Chih-Hsin Yang, MD, PhD, professor of oncology at the National Taiwan University, who presented the findings at this year’s ASCO conference.
Only 5 to 15 percent of western lung cancer patients have the mutation. For these particular patients, median survival is roughly two years if they are treated before the disease becomes metastatic, Yang added.
“Cancer is a chronic disease already, but we are still a bit distant from the cure for patients who have already metastasized,” Yang said.
Complex and Attentive Follow-Up Care is Needed
One indicator of the success scientists expect to have in managing patients with chronic cancer is the creation of ASCO’s survivorship committee. Those patients who are cured of cancer, or who experience cancer as a chronic disease, are likely to need additional follow-up, and may be at risk for secondary cancers and other health risks.
While oncologists already have experience treating long-term survivors of pediatric cancer, most of whom are now cured outright of many previously devastating forms of cancer, about one-third of adult patients who achieve five-year survival will still have cancer, according to Melissa M. Hudson, MD, member of the department of oncology at St. Jude Children’s Research Hospital in Memphis.
“ASCO feels it’s their responsibility to provide guidance for long-term cancer survivors through guidelines that have been established after monitoring populations, or after an intervention has been proven to reduce morbidity and mortality, but we don’t have that kind of data yet from well-designed trials,” said Hudson, who is also the immediate past-chair, and current member of ASCO’s survivorship committee, which was established in 2011.
However, within the past year, the committee has become convinced that even in the absence of an intervention that reduces mortality among long-term cancer survivors, patients need guidance for what their follow-up care should be.
“We’re doing breast cancer first, and hopefully we will have a guidance out in the next 12 to 24 months, because there is a huge cry for how can we get information as fast as possible to these survivors,” explained Hudson.