“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.”
“ASCO and Friends of Cancer Research (Friends) applaud the National Cancer Institute’s (NCI) recent revision of its clinical trial protocol template to broaden eligibility criteria for cancer clinical trials. The protocol template was expanded to help increase the opportunity for participation in NCI-funded clinical trials for patients with certain health-care conditions, as well as to provide an opportunity for patients younger than age 18 to participate in adult clinical trials in certain circumstances.”
“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.”
“In recent years, many Americans have embraced vitamin D and fish oil pills, their enthusiasm fueled by a steady trickle of suggestive research studies linking higher levels of vitamin D with lower rates of cancer and other ills, and fish consumption with reduced heart disease.
“Now a large and rigorous government-funded randomized trial — the only such study of omega-3 fish oils ever carried out in healthy adults, and the largest trial ever done of high-dose vitamin D — has found the supplements do not lower cancer rates in healthy adults. Nor do they reduce the rate of major cardiovascular events, a composite of heart attacks, strokes and deaths from cardiovascular disease. The trial is of the kind considered the gold standard in medicine.”
“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.”
“Combination neoadjuvant immune checkpoint blockade therapy yielded promising outcomes in high-risk resectable melanoma, although toxicity was an issue, according to a phase II trial.
“The combination of ipilimumab (Yervoy) and nivolumab (Opdivo) led to improved progression-free survival (PFS), distant metastasis-free survival (DMFS), and overall survival (OS) versus neoadjuvant nivolumab monotherapy in 23 patients with high-risk resectable melanoma, reported Jennifer A. Wargo, MD, of MD Anderson Cancer Center in Houston, and colleagues in Nature Medicine.”
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…
“The combination of encorafenib and binimetinib resulted in longer overall survival (OS) compared with vemurafenib in patients with BRAF V600–mutant melanoma, according to results of the COLUMBUS trial. Combined with an earlier report showing improved progression-free survival (PFS), this suggests the regimen should become an important option in this setting.
“Small-molecule BRAF inhibitors, originally introduced as monotherapy, offered improvements in outcomes for these melanoma patients. ‘However, response durations were short and BRAF inhibitor treatment was associated with the development of squamous cell skin cancer and other skin toxicities related to paradoxical MAPK pathway activation,’ wrote study authors led by Reinhard Dummer, MD, of University Hospital Zurich in Switzerland. Combinations of BRAF and MEK inhibition have improved the situation further, but better treatment options are still needed.”
“A phase I trial found promising activity and good tolerability with the combination of pembrolizumab and a stimulant of Toll-like receptor 9 (TLR9) known as SD-101 in patients with unresectable or metastatic melanoma, particularly in those who had not received prior anti–programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) therapy.
“PD-1/PD-L1 inhibition has improved outcomes in metastatic melanoma, and studies have indicated that combination therapy can increase immune responses further. “Despite the improvement in response rates with combination immunotherapy, a large unmet need remains,” wrote study authors led by Antoni Ribas, MD, PhD, of the University of California, Los Angeles, Jonsson Comprehensive Cancer Center.”