Immunotherapy scores a first win against some breast cancers

For the first time, one of the new immunotherapy drugs has shown promise against breast cancer in a large study that combined it with chemotherapy to treat an aggressive form of the disease. But the benefit for most women was small, raising questions about whether the treatment is worth its high cost and side effects.

Results were discussed Saturday at a cancer conference in Munich and published by the New England Journal of Medicine.


Drugs called checkpoint inhibitors have transformed treatment of many types of cancer by removing a chemical brake that keeps the immune system from killing tumor cells. Their discovery recently earned scientists a Nobel Prize. Until now, though, they haven’t proved valuable against breast cancer.


The new study tested one from Roche called Tecentriq plus chemo versus chemo alone in 902 women with advanced triple-negative breast cancer. About 15 percent of cases are this type — their growth is not fueled by the hormones estrogen or progesterone, or the gene that Herceptin targets, making them hard to treat.

Women in the study who received Tecentriq plus chemo went two months longer on average without their cancer worsening compared with those on chemo alone — a modest benefit. The combo did not significantly improve survival in an early look before long-term follow-up is complete.

Previous studies found that immunotherapies work best in patients with high levels of a protein that the drugs target, and the plan for the breast cancer study called for analyzing how women fared according to that factor if Tecentriq improved survival overall.

The drug failed that test, but researchers still looked at protein-level results and saw encouraging signs. Women with high levels who received the combo treatment lived roughly 25 months on average versus about 15 months for women given chemo alone.


That’s a big difference, but it will take more time to see if there’s a reliable way to predict benefit, said Dr. Jennifer Litton of the MD Anderson Cancer Center in Houston. She had no role in running the study but enrolled some patients in it, and oversees 14 others testing immunotherapies.

“We’re really hopeful that we can identify a group of women who can get a much bigger and longer response,” she said.

Another breast cancer specialist with no role in the study, Dr. Michael Hassett at Dana-Farber Cancer Institute in Boston, said he felt “cautious excitement” that immunotherapy may prove helpful for certain breast cancer patients.

Side effects need a close look, both doctors said. Nearly all study participants had typical chemo side effects such as nausea or low blood cell counts, but serious ones were more common with the combo treatment and twice as many women on it stopped treatment for that reason.



This undated fluorescence-colored microscope image made available by the National Institutes of Health in September 2016 shows a culture of human breast cancer cells. For the first time, one of the new immunotherapy drugs has shown promise against breast cancer in a large study that combined it with chemotherapy to treat an aggressive form of the disease. Results were discussed Saturday, Oct. 20, 2018 at a European Society for Medical Oncology conference in Munich and published by the New England Journal of Medicine. AP

For the first time, one of the new immunotherapy drugs has shown promise against breast cancer in a large study that combined it with chemotherapy to treat an aggressive form of the disease. But the benefit for most women was small, raising questions about whether the treatment is worth its high cost and side effects.

Results were discussed Saturday at a cancer conference in Munich and published by the New England Journal of Medicine.


Drugs called checkpoint inhibitors have transformed treatment of many types of cancer by removing a chemical brake that keeps the immune system from killing tumor cells. Their discovery recently earned scientists a Nobel Prize. Until now, though, they haven’t proved valuable against breast cancer.


The new study tested one from Roche called Tecentriq plus chemo versus chemo alone in 902 women with advanced triple-negative breast cancer. About 15 percent of cases are this type — their growth is not fueled by the hormones estrogen or progesterone, or the gene that Herceptin targets, making them hard to treat.

Women in the study who received Tecentriq plus chemo went two months longer on average without their cancer worsening compared with those on chemo alone — a modest benefit. The combo did not significantly improve survival in an early look before long-term follow-up is complete.

Previous studies found that immunotherapies work best in patients with high levels of a protein that the drugs target, and the plan for the breast cancer study called for analyzing how women fared according to that factor if Tecentriq improved survival overall.

The drug failed that test, but researchers still looked at protein-level results and saw encouraging signs. Women with high levels who received the combo treatment lived roughly 25 months on average versus about 15 months for women given chemo alone.


That’s a big difference, but it will take more time to see if there’s a reliable way to predict benefit, said Dr. Jennifer Litton of the MD Anderson Cancer Center in Houston. She had no role in running the study but enrolled some patients in it, and oversees 14 others testing immunotherapies.

“We’re really hopeful that we can identify a group of women who can get a much bigger and longer response,” she said.

Another breast cancer specialist with no role in the study, Dr. Michael Hassett at Dana-Farber Cancer Institute in Boston, said he felt “cautious excitement” that immunotherapy may prove helpful for certain breast cancer patients.

Side effects need a close look, both doctors said. Nearly all study participants had typical chemo side effects such as nausea or low blood cell counts, but serious ones were more common with the combo treatment and twice as many women on it stopped treatment for that reason.


Three of the six deaths from side effects in the combo group were blamed on the treatment itself; only one of three such deaths in the chemo group was.

Cost is another concern. Tecentriq is $12,500 a month. The chemo in this study was Celgene’s Abraxane, which costs about $3,000 per dose plus doctor fees for the IV treatments. Older chemo drugs cost less but require patients to use a steroid to prevent allergic reactions that might interfere with the immunotherapy. Abraxane was chosen because it avoids the need for a steroid, said one study leader, Dr. Sylvia Adams of NYU Langone Health.

The study was sponsored by Roche and many study leaders consult or work for the company or own stock in it. /cbb

source: technology.inquirer.net

Cancer gene mutation more complex than previously thought: study

LONDON (Reuters) - Taking a sample or biopsy from just one part of a tumor might not give a full picture of its genetic diversity and may explain why doctors, despite using genetically targeted drugs, are often unable to save patients whose cancer has spread, scientists said.

A study by British researchers found there are more genetic differences than similarities between biopsies taken from separate areas of the same tumor, and yet further gene differences in samples taken from secondary tumors.

That might help explain why, despite recent development of a wave of highly targeted drugs designed to tackle cancers of specific genetic types, the prognosis remains poor for many patients with so-called solid-tumor disease like breast, lung, or kidney cancer that has spread to others parts of the body.

But the researchers, whose study was partly funded by charity Cancer Research UK and published in the New England Journal of Medicine, said it also pointed to a way forward.

The team carried out the first ever genome-wide analysis of the genetic changes or faults in different regions of the same tumor.

They looked at four patients with cancer in their kidneys, taking samples from different regions of the primary tumor and also from other organs where the tumor had spread.

They found that the majority of gene faults, around two-thirds, were not the same in one sample as in another, even when the biopsies were taken from the same tumor.

Samples taken from secondary tumors - which are a result of the disease spreading to other parts of the body - had yet more different genetic faults, suggesting that basing treatment decisions on just one primary tumor sample is not sufficient.

"We've known for some time that tumors are a patchwork of faults, but this is the first time we've been able to use cutting-edge genome sequencing technology to map out the genetic landscape of a tumor in such exquisite detail," said Charles Swanton, of University College London's cancer institute, who led the study and presented its results at a briefing in London on Tuesday.

He said they had uncovered "an extraordinary amount of diversity" at a genetic level both within tumors and within a single patient, with more differences between biopsies from the same tumor than similarities.

"The next step will be to understand what's driving this diversity in different cancers and identify key driver mutations that are common throughout all parts of a tumor," Swanton said.

PERSONALISED MEDICINE

Genetic profiling of patients and their tumors has become more common in cancer treatment in wealthy countries as drug companies develop new generations of so-called "personalized medicines" that target cancers with specific genetic features.

Roche's blockbuster breast cancer drug Herceptin is designed to treat only women who make too much of the HER2 protein, for example, while Novartis's Afinitor targets mTOR, a protein that acts as an important regulator of tumor cell division, blood vessel growth and cell metabolism.

James Larkin, an oncologist at London's Royal Marsden Hospital who also worked on the study, said the findings suggest the reality of personalized cancer treatment is far more complex than previously thought.

"The molecular changes that drive the growth of the cancer once it has spread may be different from those that drive the growth of the primary tumor," he said.

The researchers compared genetic faults in various tumor samples taken from the four patients.

They found 118 different mutations - 40 of which were "ubiquitous mutations" found in all biopsies, 53 "shared mutations" that were found in most but not all biopsies, and 25 "private mutations" only found in a single sample.

By analyzing where the shared mutations were in relation to the whole tumor, the researchers were able to trace the origins of certain subtypes of cancer cells back to what they called key "driver mutations." This allowed them to create a map of how the pattern of faults might have evolved over time.

Swanton likened the findings to a tree, in which the trunk is the primary tumor and the branches the secondary tumors from the cancer's spread.

While he stressed the results would need to be replicated with larger numbers of patients and in different types of cancer, he said these early indications showed "the importance of targeting common mutations found in the trunk of the tree as opposed to those found in the branches."

"It may also explain why surgery to remove the primary kidney tumor can improve survival," he added, since cutting out a tumor reduces the risk that cells resistant to drug treatment could go on to re-grow the tumor or spread elsewhere.

source: mb.com.ph

Tai chi may help balance in people with Parkinson's

The slow, controlled motions of tai chi can help the impaired balance of people with mild or moderate Parkinson's disease, and the improvements persist for at least three months, according to a small study out Wednesday.

Compared with people who received stretching exercises, tai chi practitioners had fewer falls, longer strides and better balance, researchers found.

"Tai chi fits very well to address the problem Parkinson's disease patients face," said Fuzhong Li of the Oregon Research Institute in Eugene, whose findings appear in the New England Journal of Medicine.

Difficulty walking and remaining standing are hallmarks of Parkinson's, which results from the death of brain cells that generate the chemical dopamine.

"We're not going to get rid of the symptoms. It's not a drug. It can't cure the disease. But, in my view, it can slow down the progression of the disease," Li told Reuters Health.

Although not all studies agree, other research has shown that because it is a balance-based exercise, tai chi may help improve strength and reduce falls in older adults. But there are few large studies in Parkinson's patients.

Li and his colleagues sent 195 seniors, all from Oregon, to one of three classes that met twice weekly for an hour. All could stand unaided, but some needed a device to help them walk.

The tai chi exercises were designed to improve balance with a controlled displacement of the center of mass. Resistance training with ankle weights and weighted vests was used in a second group to strengthen muscles important to posture, balance and gait. A third group had classes that involved gentle stretching.

People in all three groups started off with similar 64-point scores on a 100-point scale that measured how far they could lean or shift their center of gravity without falling.

But after 24 weeks of classes, those in the stretching group saw their average score drop by two points, indicating some deterioration in their condition.

The typical score rose by four points in the resistance group and by 10 points among the tai chi practitioners.

All of the volunteers were tested when their medication was working and their symptoms were controlled.

The improvement with tai chi was even more significant on a test to see how far the person could move toward a target without extraneous movement.

Stride length, walking velocity, knee movement and other measurements also showed more improvement. And people who did tai chi reported only 62 total falls during the training—less than half of what the other groups reported.

Three months after the classes stopped, some of the benefits persisted. For instance, tai chi practitioners had 60 percent fewer falls than the resistance-training group and 69 percent fewer than the stretching group.

"This is the first time to my knowledge that a study was able to show some durability as a treatment for balance," Li said. "This was a big gap in a research field that didn't have any follow-up data with an exercise regimen."

There was, however, some slippage. The average score for leaning and shifting gravity, which had improved by 10 points in the tai chi practitioners, appeared to drop slightly.

The nice thing about tai chi, he said, is that "this is not equipment-dependent. It can be practiced at any place, at any time."

Parkinson's affects at least 500,000 Americans, most of them elderly, according to the National Institute of Neurological Disorders and Stroke, which funded the new study.

The cost of tai chi classes varies, but prices are typically similar to those of other types of exercise classes. –Reuters

source: gmanetwork.com