Chemotalk Newsletter, Vol. 89 September 1, 2015
News for September...
LIMITED RESECTION NOT EQUIVALENT TO LOBECTOMY IN ELDERLY NSCLC PATIENTS
Limited resection is not as effective as lobectomy in older patients with early-stage NON-SMALL-CELL LUNG CANCER (NSCLC), according to a new study. Segmentectomy may provide similar outcomes, however, specifically in patients with ADENOCARCINOMA.
Though NCCN guidelines currently recommend lobectomy with systematic lymph node sampling for stage IA disease, several recent observational studies have shown similar survival with limited resection (wedge resection or segmentectomy), in particular among older lung cancer patients. ³Consequently, elective limited approaches are increasingly used for stage IA NSCLCs,² wrote study authors led by Rajwanth R. Veluswamy, MD, of Icahn School of Medicine at Mount Sinai in New York.
In the new study 2,008 patients with adenocarcinoma and 1,139 patients with SQUAMOUS CELL CARCINOMA were included from the SEER-Medicare registry; all were older than 65 years of age. Of those, 27% and 32%, respectively, underwent limited resection. Results of the analysis were published in the Journal of Clinical Oncology.
Among adenocarcinoma patients, those treated with limited resection were more likely to be older (P < .001), less likely to be married (P < .001), had more comorbidities (P < .001), and had smaller tumors (P < .001). In squamous cell carcinoma patients, limited resection patients were again older (P = .04), more likely to be women (P = .004), and had higher comorbidity scores (P < .001).
Limited resection was not equivalent to lobectomy with regard to overall survival in invasive adenocarcinoma patients, with a hazard ratio (HR) of 1.21 (upper 95% confidence interval [CI], 1.34; an upper 95% CI of 1.25 or below was considered equivalent). It was also not equivalent in these patients with regard to lung cancerspecific survival, with an HR of 1.66 (upper 95% CI, 1.96). This was similar in squamous cell carcinoma patients, with an HR for overall survival of 1.21 (upper 95% CI, 1.39) and for lung cancerspecific survival of 1.41 (upper 95% CI, 1.79).
There was one subgroup that showed equivalence between treatments: patients with adenocarcinoma treated specifically with segmentectomy had equivalent overall survival, with an HR of 0.97 (upper 95% CI, 1.07), and cancer-specific survival, with an HR of 0.89 (upper 95% CI, 1.07), to those treated with lobectomy. This was not the case in squamous cell carcinoma patients.
³Our results highlight the importance of tumor histology as a determinant of long-term outcomes for patients with early-stage NSCLC,² the authors concluded. They noted the limitation of a lack of randomization, but wrote that these results are important especially given the increasing uptake of lung cancer screening ³and the expected growth in the number of early-stage NSCLCs.²
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DECADES OF DATA FAIL TO RESOLVE DEBATE ON TREATING TINY BREAST LESIONS
By Gina Kolata
More than 30 years after the widespread use of mammogram set off a surge in the detection of tiny lesions in milk ducts there is still debate about how -- or even whether -- to treat them In an era when there has been so much study of how to treat more advanced CANCER, it might seem odd that there is so much uncertainty about these minute sprinklings of abnormal cells, often called Stage 0 cancer which some say are not cancers at all.
The latest round of controversy was set off by a paper published in JAMA Oncology that analyzed 20 years of data on 100,000 women who had the condition, which is also known as ductal carcinoma in situ, or D.C.I.S. The majority had lumpectomies (with or without radiation) and most of the others had mastectomies. The death rate from BRAST CANCER of these patients, regardless of their choice of treatment, over the next 20 years was about the same as the lifetime risk in the general population of women 3.3%.
The study's authors and other leading researchers in the field said the data indicates that treatment has not made much of a difference if any, for the tens of thousands of women a year who are told they have this condition. (Last year about 60,000 in the United States got a D.C.I.S. diagnosis.) One piece of evidence is that the women who had mastectomies had their entire breast cut off and so if D.C.I.S. was, as many thought, a precursor to cancer or an early cancer, their death rate should have been lower than it was for women who had lumpectomies that could have left D.C.I.S. cells behind.
Another major clue is that though tens of thousands of cases of D.C.I.S. were being diagnosed ad aggressively treated each year, there seemed to be no substantial impact on the incidence of invasive breast cancers found annually in the general population. About 240,000 were diagnosed with it last year. If treating D.C.I.S. was supposed to fend off invasive breast cancer, the incidence of invasive breast cancer should have plummeted once D.C.I.S. was found and treated, the experts said.
That has intensified questions about what D.C.I.S. really is -- cancer, precancer, a risk factor for cancer?
Before mammography only a few hundred women a year were diagnosed with DC.I.S. It was a condition almost always noticed only on autopsies. Once radiologists began finding D.C.I.S., though, doctors were faced with a dilemma.
At first glance it seemed wonderful to fin the lesions. The cells looked like cancer although thy had not broken through the wall of the milk duct into the surrounding breast tissue. Their discovery it seemed offered a chance to cut out cancers long before then could be felt as lumps. But there was a problem, noted Dr. Barnett Kramer, director of the division of cancer prevention at the National Cancer Institute. With D.C.I.S. the abnormal cells were not just a well-defined clump. Instead abnormal cells often were sprinkled along the length of the milk duct. What to do?
The obvious answer seemed to be to cut off the entire breast Doctors had the example of abnormalities detected by the Pap test: Cutting out early lesions on the cervix prevented deaths fro invasive CERVICAL CANCER. It made sense to do something similar to prevent breast cancer deaths said Dr. Barron Lerner, a historian of medicine at New York University Langone Medical Center.
Yet this was happening at a time, in the 1980s and early 1990s, when women with invasive cancers were told they could have a lumpectomy instead of a mastectomy. "It's very weird, thinking back now. We treated the more aggressive disease less aggressively than we treated the less aggressive disease," said Dr. Otis Brawley, chief medical officer for the American Cancer Society.
Unlike the situation with invasive breast cancer no one did clinical trials in D.C.I.S. comparing, say lumpectomies plus radiation to mastectomies, or watchful waiting and assessing whether there was a difference in the risk of cancer reappearing in the breasts. But as doctors became comfortable treating invasive cancers with lumpectomies, they began treating D.C.I.S. that way, too.
Over the years investigators have come to conclude that the old model of cancer -- that a few aberrant cells will grow spread and inevitably become a deadly cancer if not destroyed -- is wrong. Small clumps of abnormal cells may just stop growing, scientists now know. Even invasive cancers do not always grow Some regress or disappear. That is especially true to PROSTATE CANCER where as many as half of all cancers found with screening will not progress if they are simply left alone But it also seems true in breast cancer, researchers say.
Doctors used to think that cancers that recur at the original site in the breast after treatment are likely to spread outside the breast and kill. That, too, has turned out not to be true. Some cancers metastasize and others remain in the breast and never leave it, Dr. Kramer said The two types of cancers have different properties. That is why radiation after a lumpectomy does not reduce the death rate from breast cancer although it reduces the recurrence of invasive cancer in the breast.
"Treatment that reduces recurrence in the breast is not a good surrogate for reducing the risk of death from breast cancer," Dr. Kramer said. "This gets to the issue of how counterintuitive cancer is."
With D.C.I.S. women have a worse prognosis if they are black, under 40, or have tumors with molecular markers like those found in more aggressive invasive cancers. They may benefit from treatment, but so far no one has done a large clinical trial asking if these treatments prevent breast cancer deaths for the rest of the women with D.C.I.S. Are the surgical treatments better than watchful waiting and perhaps drugs to reduce overall breast cancer risk?
Medical experts say it is highly unlikely such a clinical trial will ever be done. Because the risk of dying of breast cancer is so low for women treated for D.C.I.S., the study would take 10 to 20 years and involve tens of thousands of women assuming it would even be possible to recruit so many who would agree to have their treatment decided at random. And assuming somehow there were funds to pay for it. And when it was done doctors might well argue that the study used old-style medicine, that things had progressed since then and so the results were no longer valid
"Welcome to the world of dealing with low-probability events," said Dr. H. Gilbert Welch, a professor of medicine at Dartmouth and author of "Less Medicine, More Health."
"I think it is a classic example of what is and will only increasingly become a recurrent problem in medicine," he added. "The question about what to do -- if anything -- are fundamentally difficult.
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MEDICARE REVERSING ITSELF WILL PAY MORE FOR AN EXPENSIVE NEW CANCER DRUG
By Robert Pear
The Obama administration has decided that Medicare will pay for one of the newest, most expensive CANCER medications, which costs about $178,000 for a standard course of treatment.
Patients, doctors, hospital executives and insurers have expressed concern about the high cost of prescription drugs, especially new cancer medicines and treatments tailored to the genetic characteristics of individual patients. Medicare officials recognized the cost and value of one such product, the anti-cancer drug Blincyto, by agreeing to make additional payments for it starting October 1. He drug is made by Amgen for patients with a particularly aggressive form of LEUKEMIA.
The decision suggests a new willingness by Medicare to help pay for promising therapies that are still being evaluated. It is also significant because Medicare officials reversed themselves on every major scientific issue involved, After receiving pleas from Amgen, and a dossier of scientific evidence, the officials agreed that the drug was a substantial improvement over existing treatments for some patients.
At issue are special "add-on payments" that Medicare makes to hospitals for new technology whose costs are not yet reflected in the standard lump-sum amounts that hospitals receive for treatment patients with a particular disease or disorder.
In a preliminary decision in April, the Obama administration said it did not intend to pay extra for Blincyto because clinical studies were "not sufficient to demonstrate" that it substantially improved the treatment of Medicare patients with ACUTE LUMPHOLASTIC LEUKEMIA, a cancer of the blood and bone marrow. Medicare officials said Amgen's application was based on data from "a small sample group of patients whose age demographic is much younger than the age demographic of eligible Medicare beneficiaries."
But in a final rule published in the Federal Register the administration says it received "additional information and input" from Amgen and other experts and now agrees with their arguments.
Blincyto "is not substantially similar" to other drugs available to leukemia patients, the administration said, and it "represents a substantial clinical improvement over existing treatment options."
Jane E. Wirth, 59, of Reno, Nev., a former preschool teacher, said her cancer was in remission after 28 days of treatment with Blincyto also known as blinatumomab.
"It was amazing to me that it could work so well so quickly," Ms. Worth said in an interview. "I had just spent a month going through standard CHEMOTHERAPY, which did not make the cancer go away. It seemed to hopeless."
The drug, engineered from two antibodies, harnesses the body's immune system to help fight cancer. It brings certain white blood cells close to malignant cells so the blood cells can destroy the cancer cells.
Dr. Anthony S Stein, a researcher at City of Hope National Medical Center in Duarte, Calif., who has treated more than 50 patients in clinical trials of Blincyto, said, "It's mechanism of action is totally different fro that of any other approved drug."
After the Food and Drug Administration approved Blincyto in December, Amgen said the price would be about $178,000 for the recommended two 28-day cycles of treatment, each followed by a two-week break. Medicare says it will now allow a "new technology add-on payment" to hospitals for a fraction of that amount, up to $27,000. Actual payments will vary based on the length of a patients hospital stays
A cycle of treatment begins with intravenous infusions in a hospital. Patients typically continue treatments outside the hospital -- at doctor's offices, at infusion centers or at home, with the help of specially trained nurses -- and Medicare will help pay for the drug at those sites, too.
The prices of new cancer drugs often exceed $100,000 a year.
Health policy experts said that President Obama had personally expressed concern in recent weeks about high drugs prices and their impact on consumers and federal programs. In February, he asked Congress to authorize the secretary of health and human services to negotiate with manufacturers to determine prices for high-cost medicines taken by Medicare beneficiaries.
A poll by the Kaiser Family Foundation released last month found that 94% of Democrats and 84% of Republicans support allowing the federal government to negotiate with drug makers to get lower prices on medication for those beneficiaries.
Dr. Steven M. Safyer, president of Montefiore Medical Center in the Bronx, said the Obama administration should use its influence with drug companies to restrain costs. "There are a number of very important breakthroughs with pharmaceuticals that can make a difference between life and death, and the price is too high," he said.
More than 100 oncologists from cancer hospitals around the country recently issued a manifesto decrying the prices of new drugs.
"Effective new cancer therapies are being developed by pharmaceutical and biotechnology companies at a faster rate than ever before," they said in a commentary in the Journal Mayo Clinic Proceedings. But, they added, "the current pricing system is unsustainable and not affordable for many patients."
Robert E. Zirkelbach, a spokesman for Pharmaceutical Research and Manufacturers of America, the lobby for drug makers, said that new spending projections issued by the government in July undercut such claims.
"Even with new treatments and cures for hepatitis C, high cholesterol and cancer," Mr. Zirkelbach said, "sending on retail prescription medicines in projected to remain approximately 10% of U.S. Health care spending through 2024, the same percentage as in 1960." In the last two decades, he added the cancer death rate has fallen 22%, thanks in part to new medicines.
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See you in October...
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And if you have any thoughts of how this newsletter could be improved, please email me directly, at Elaine@elainejesmer.com.