Immunotherapy drugs when combined prevent melanoma progression

In a new trial, researchers have discovered that a combination of 2 immunotherapy drugs-ipilimumab and nivolumab- is capable of reversing or preventing the progression of advanced melanoma for 5 years or more in every 2 patients.

Just 10 years ago, only 1 in 20 patients with advanced melanoma would survive for 5 years- with many living for just 6-9 months.

The results of the trial,  represent the longest phase 3 trial follow-up for checkpoint inhibitor combination therapy.

In the past, metastatic melanoma was regarded as untreatable. Oncologists considered melanoma different to other cancers-- it couldn't be treated once it had spread. This is the first time we can say that the chances of being a long-term survivor of advanced melanoma are now over 50%, said one of the researcher.

Researchers incorporated 945 patients with advanced melanoma randomised into 3 groups- 314 patients received the ' double-hit' of nivolumab + ipilimumab; 316 patients received nivolumab + a placebo; and 315 patients received ipilimumab + placebo.

Each nivolumab arm was compared to ipilimumab by itself, and was administered until the disease progressed or until any side-effects became unacceptable.

The 5 year overall survival rate for the combination of nivolumab + ipilimumab was 52 %, with 74 % of those patients treatment-free after 5 years. The overall survival for nivolumab was 44 % and 26% for ipilimumab.

The Prof. explained, by giving these drugs together you're effectively taking 2 brakes off the immune system rather than one so that the immune system is able to recognise tumours it wasn't previously recognising and react to that and destroy them.

Importantly, for those patients who stopped treatment because of side-effects such as fatigue, skin rashes and diarrhea, the outcome was just as good as it was for those who were on the combination for longer.

One of the key points about immunotherapies is that the immune system can be re-educated even with a short duration of treatment. This is in contrast to other treatments like chemotherapy which can require a full course to be as effective.

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This immunotherapy combination shrinks rare, neuroendocrine

According to a new research, there is a significant clinical benefit for patients with high-grade neuroendocrine carcinoma, which is the cancer of the neuroendocrine cells that often form tumours in the lungs and along the digestive tract too.

Even though, this cancer is rare, about 12,000 people in the United States are diagnosed with it, every year. But, do you know that the general prevalence of the disease grew six-fold between 1973 and 2012? Patients with the high-grade, or rapidly growing, form have tend to have only few treatment options.

“We saw a benefit in patients with high-grade carcinoma, which is the population that really needs an effective treatment option,” said a Dr. These early results are really encouraging and intriguing. We found a clear difference in response to treatment between the high-grade and low-grade forms of this cancer type,” said the Dr.”So tumour biology makes a difference. We don`t yet know why, but we`ve opened another treatment arm of the trial to patients with just high-grade neuroendocrine carcinoma to see if we find the same response to the immunotherapy combination,” the Dr. added.

DART features an innovative ‘basket’ design which allows the testing of a single drug or drug combination in a variety of tumour types. DART, currently tests the immunotherapy combination of ipilimumab and nivolumab in patients with 37 types of rare cancers, which together make up almost a quarter of all cancers diagnosed worldwide.

Researchers enrolled 33 patients with neuroendocrine tumours. Of those 33 patients, 19 had high-grade disease. Most patients’ tumours were located in the gastrointestinal tract or the lungs. All patients received doses of ipilimumab every six weeks and doses of nivolumab every two weeks and continue on the treatment for as long as their bodies respond to the drugs. Results showed that 42 per cent of patients with the high-grade form of neuroendocrine carcinomas saw their tumours shrink partially or completely after treatment, while none of the low-grade patients did. For all the patients, 70 per cent saw their cancer spread within six months.

Patients survived a median of at least 11 months after treatment. Some patients are alive more than a year after treatment, and doctors continue to track their progress.”There’s a myth that you can’t successfully complete clinical trials in rare cancers. Researchers think it’s too hard to find patients. But DART shows us that we can run rare cancer trials, and enroll patients quickly and learn if therapies are effective in rare diseases,” he said.”We can also offer investigational drugs to patients’ right in their communities. They don’t necessarily need to travel to a cancer centre to get enrolled in a clinical trial.”

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'Drastic' HIV decrease prompted by cancer drug in lung cancer patient

Doctors  have found the first evidence that a drug normally used to treat lung, kidney or skin cancer may be able to eradicate HIV-infected cells in people with the AIDS virus.

In a case described as potentially exciting by scientists who also advised caution, doctors said a 51-year old man given nivolumab -  saw a “drastic and persistent decrease” in the reservoirs of cells where HIV normally hides away and evades standard treatments.

The case was detailed in a report , where the same doctors also gave a case study of another patient treated with Opdivo who did not show any HIV benefit.

“We must remain careful, especially because this is only one case,” said  a professor .“This is the first case of such a drastic decrease of the HIV reservoir (but) we have...another case where there was no decrease.”

Some 37 million people worldwide have the human immunodeficiency virus (HIV) that causes AIDS. Scientists have for years been trying to find a way of clearing HIV reservoirs with a view to being able to eradicate the virus completely and cure AIDS.

These reservoirs of HIV-infected cells are found in the immune system in places like the brain, bone marrow and genital tract. They lie hidden and dormant, and can’t be reached with standard anti-retroviral therapy HIV treatments.

If standard treatment is stopped or interrupted, the reservoirs seize the chance and the virus starts to replicate and infect more cells, rendering the patient’s immune system too weak to fight back.

“Increasingly, researchers have been looking into the use of certain drugs that appear to re-activate the latent HIV-infected cells,” the Dr. said. “This could have the effect of making them visible to the immune system, which could then attack them.”

Opdivo, or nivolumab is a PD-1 inhibitor, designed to help the body’s own immune system fend off cancer by blocking a protein called PD-1. It is one of several cancer immunotherapy drugs made by drugmakers  that work in similar way.

In this case, the 51-year-old man had received 31 injections of nivolumab every 14 days since December 2016. He was diagnosed HIV-positive in 1995 and diagnosed with non-small cell lung cancer in May 2015.

After his first injection, the man’s HIV infection load, which had been low, increased progressively up until day 45, then fell back again. At the same time, the doctors explained - the activity of his immune system increased.

By day 120, the treatment had “resulted in the drastic decrease in the HIV reservoir...leading to a sustained reduction of the HIV reservoirs,” the Dr. said.

An infectious diseases expert said the case was “potentially exciting”. But like others, he advised caution.

”It’s difficult to speculate at this stage why the second patient did not show the same response,“ he said in an emailed comment. ”Differences in the size of the latent reservoir or genetic differences between individuals, affecting their ability to mount immune responses to HIV, might be important factors.

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Study finds good gut bacteria improves cancer patient's response to immunotherapy

In a recent study, a group of researchers found a link between an individual's gut bacteria and their response to anticancer immune checkpoint inhibitor therapy (ICT).

The researchers analyzed the gut bacteria of 39 melanoma patients who were treated with immunotherapies and found a strong association between a good response and the presence of particular bacteria. While talking about the research, senior author  said, "Our research suggests there were certain good-guy bacteria that are needed to optimize the effectiveness of checkpoint inhibitors.
These bacteria somehow prime your immune system so that it's better able to attack cancer cells and kill them." Although ICT achieves durable remission in up to 50 percent of patients with metastatic melanoma, a significant proportion of patients fail to respond or experience severe autoimmune adverse effects, the researchers note.

A person with metastatic melanoma volunteered for the study to identify the link. The participant's metastatic melanoma was discovered on his lungs while he was fighting pneumonia. He was treated with an every-other-week infusion of nivolumab, an immunotherapy drug that acts by lifting a brake on the immune system, allowing the body's natural defenses to go into overdrive.

Researchers found he had the beneficial gut bacteria and suspect this microbiome contributed to the outcome. As a group, patients who responded well to the immunotherapy had three specific bacteria:
- Bacteroides thetaiotaomicron
- Faecalibacterium prausnitzii
- Holdemania filiformis
After identifying the link, scientists looked for a potential reason for the association between the helper bacteria and immunotherapy effectiveness. Dr. explained, "Is it something the bacteria are making? We examined metabolites in these subjects and found the strongest correlation between anacardic acid, present in cashews and mangoes, and the beneficial bacteria."

Now the researchers are planning to follow-up on the current study with larger clinical studies.

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Promising therapies that can help battle this terminal illness

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Going through cancer treatment and surviving cancer is an arduous journey.

With the evolution of medicine, researchers and scientists have been able to find several ways to deter cancer cells from spreading. But, across the world scientists are still struggling to find foolproof ways of prevention and medication that can cure the fatal disease.

While the disease in itself is fatal, treatment for cancer is painful as well. Harsh drugs, radiation and chemotherapy often leave patients' health in a fragile state. And as newer ways of battling cancer are being introduced, on World Cancer Day, we look at what researchers suggest are promising treatments for the disease:

Representational image.

Adoptive T-cell Therapy: Thymocyte cells or T-lymphocytes are a type of lymphocyte play a key role in immunity. And researchers at the UW School of Medicine say that, "Adoptive T-cell therapy (helps) achieve greater number of T cells than what could be obtained by vaccination alone. The tumor specific T cells are then infused into patients with cancer in an attempt to give their immune system the ability to overwhelm remaining tumor."
According to the researchers, there are several types of T-cell therapy that are being developed that include engineering cells that identify and attack tumours.
Nature says that while T-cell engineering is a cause for optimism, development of more potent T-cells have been stopped by safety concerns.
Immune checkpoint inhibitors: It is when our immune system cannot distinguish between cancer and normal cells is when cancer cells grow. And one way to stop the growth of cancer cells is to use drugs that hide from the "checkpoints" the immune system uses to separate normal cells from foreign cells.
According to cancer.org, antibodies like Pembrolizumab, Nivolumab and Ipilimumab help treat certain types of cancers. The research states that such therapy has shown to have helped cancers like melanoma and non-small cell lung cancer.
Targeted therapy: It targets the changes in cancer cells, the way the divide and spread. According to cancer.gov there are two types of targeted therapy that are done with the use of small-molecule drugs and monoclonal antibodies. The first one is used for targets that are inside cells while the second one attaches itself on the outside of the target.
According to research, this treatment helps destroy cancer cells, stop them from growing, kills them and starve them of hormones that they need to grow.
Hormone therapy with Goserlin: breastcancercare.org states that this drug can be used to treat "women whose breast cancer is sensitive to the female hormone oestrogen – known as oestrogen receptor positive or ER+ breast cancer." It is administered through subcutaneous injections and the frequency depends on the severity of the cancer.
Goserlin uses ovarian suppression or the switching off of production of Oestrogen, since some cancer cells use Oestrogen to grow.