Cancer treatments that use a strategy called immune checkpoint blockade (ICB) have entered clinical practice in a big way, with six drugs now approved by the U.S. Food and Drug Administration (FDA) for a variety of cancers. These drugs release “brakes” on the immune system, boosting its ability to kill cancer cells. Specifically, they target the proteins PD-1 or CTLA-4, which are found on the immune system’s T cells, or the protein PD-L1 on tumor and other cells. Patients’ response rates, however, have been lower than hoped for in most cancers.
Much research and discussion has focused on analysis of particular features in tumors themselves that predict how they might respond to ICB. However, because ICB drugs act on immune system proteins, it is clear that each patient’s immune system is a major player in shaping response to treatment, and that certain tumor-independent features are at play. Here’s what we know about seven factors besides tumors themselves that may predict a patient’s response to ICB: Continue reading…
“People with a type of skin cancer who consumed a high-fiber diet responded better to immunotherapy treatment than those with poorer diets, according to data presented at a media preview of the American Association for Cancer Research (AACR) annual meeting.
“Melanoma is a type of skin cancer which although very treatable if caught early, still kills approximately 9,000 Americans a year, mainly people who are diagnosed a more advanced stage of disease where the cancer has spread to other parts of the body.”
It has been over a year since I last wrote about new developments in treatment of melanoma, and it is time for an update. There is certainly some good news for melanoma patients!
Neoadjuvant (before surgery) treatments for resectable melanoma
Stage III—and more rarely, stage IV—melanoma tumors that have not spread widely can be sometimes treated surgically. Last year a small clinical trial showed that, in BRAF-mutant melanoma, treatment with the BRAF/MEK inhibitors dabrafenib and trametinib (D/T) before and after surgery provides a significant improvement over just post-surgery treatment, by preventing later recurrence.
Later in 2018, researchers reported that using the immune checkpoint drugsnivolumab and ipilimumab prior to surgery led to tumor reduction in 73% of patients treated in a clinical trial. After surgery, they remained disease-free for 2 years (the reported time of observation). Treatment with nivolumab alone was not nearly as active in this randomized trial, with only 25% of patients responding to neoadjuvant nivolumab; still, 75% were disease-free within the 2-year observation period.
An interesting trial tested a single dose of the drug pembrolizumab given three weeks prior to surgery. Of 27 patients who received this single infusion, eight (29%) had a complete or major pathological response, meaning that their tumors were reduced by 90% or more. These eight patients continued on pembrolizumab after surgery and were disease-free for over 2 years. Continue reading…
“Instructing the immune system to recognize and kill tumours, an approach termed cancer immunotherapy, has transformed the clinical treatment of certain types of malignancy. Prominent among these therapies are immune-checkpoint inhibitors, which block the action of proteins that dampen immune-cell responses against tumours. For example, antibodies can be used to interfere with the inhibitory protein PD-1, which is present on T cells, a type of immune cell that attacks tumours. Immune-checkpoint inhibitors have been most successfully used to treat cancers, such as melanomas, that are well infiltrated by T cells and have a large number of genetic mutations. A subset of these mutations might generate neoantigens — altered protein sequences that are uniquely produced in cancer cells and are recognized as foreign by the immune system.”
“In a new study by Yale Cancer Center, scientists suggest that as the number of clinical trials in cancer immunotherapy grows exponentially, some caution should be exercised as we continue to better understand the biology of these new therapeutic targets. The findings are published today in the journal Cell.
“Researchers around the world have been racing to create therapies that unleash the power of our immune systems against cancer. The most successful of these immunotherapies, which target a molecular pathway known as PD-1/PD-L1, have brightened the landscape for many people suffering with lung cancer and other types of tumors.”
“Cancer has an insidious talent for evading the natural defenses that should destroy it. What if we could find ways to help the immune system fight back?
“It has begun to happen. The growing field of immunotherapy is profoundly changing cancer treatment and has rescued many people with advanced malignancies that not long ago would have been a death sentence.”
“Individuals with an inherited form of skin cancer often have a poor prognosis. The type of immunotherapy that was awarded this year’s Nobel Prize in Physiology or Medicine is, however, particularly effective in this patient group, research from Karolinska Institutet in Sweden shows. The study is published in the Journal of Medical Genetics.
“Congenital mutations of the CDKN2A gene are the strongest known risk factors for inherited skin cancer. Individuals with melanoma who carry mutations in this gene also have poor prognosis, according to previous research.”
Immunotherapy includes a number of strategies that harness the immune system to help treat disease. Immunotherapy for cancer, as we know it, now relies on the activation of specific immune system cells known as T cells. Cancer drugs called immune checkpoint inhibitors act by removing the brakes imposed on T cells by tumors or by the body’s natural mechanisms for limiting their activation to prevent autoimmune disease.
In recent years, the U.S. Food and Drug Administration (FDA) has approved several immune checkpoint drugs for the treatment of various cancers. These drugs target proteins involved in activating the T cell response: PD-1, PD-L1, and CTLA4. Many clinical trials are testing drugs that target other immune checkpoint proteins (OX40, B7-H3, and LAG3, to name just a few), but no notable successes have been reported so far.
Now, some clinical investigators have turned their attention to a different arm of the immune system that could help treat cancer. Continue reading…
“AstraZeneca’s immunotherapy drug Imfinzi cut the risk of death in patients with mid-stage lung cancer by nearly a third in a closely watched clinical study, reinforcing the case for using the drug in earlier disease.
“The encouraging overall survival data boosts prospects for a medicine that was approved this week in Europe and has already had a promising U.S. commercial launch, based on its ability to slow disease progression.”