“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.”
“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.”
“Combined immunotherapy with two checkpoint inhibitors — nivolumab (Opdivo, Bristol-Myers Squibb) and ipilimumab (Yervoy, Bristol-Myers Squibb) — has shown ‘clinically meaningful’ efficacy in patients with asymptomatic, untreated melanoma metastases to the brain, according to a report regarding new data from the CheckMate 204 open-label phase 2 study.
” ‘Although current practice is to start with surgery, stereotactic radiotherapy, or both followed by immunotherapy or targeted agents, our results support the initiation of immunotherapy to achieve prompt control of both extracranial and brain metastases,’ write the authors.”
“Researchers at the Johns Hopkins Kimmel Cancer Center and the Bloomberg~Kimmel Institute for Cancer Immunotherapy (BKI) released a study investigating the use of combination checkpoint immunotherapy in the treatment of a lethal form of advanced prostate cancer. The study suggested a genetic subset of prostate cancer may benefit from this form of immunotherapy.
Immune checkpoint inhibitor drugs that target the proteins PD-1 and PD-L1 are by now well established in the treatment of non-small cell lung cancer (NSCLC). In 2015, the U.S. Food and Drug Administration (FDA) approved nivolumab (Opdivo), an anti-PD-1 drug, for treatment of patients with metastatic NSCLC who progressed or relapsed after platinum-based chemotherapy. Atezolizumab (Tecentriq), an anti-PD-L1 drug, was approved in 2016 for treatment of NSCLC patients in the same situation. In October 2016, the FDA approved Pembrolizumab (Keytruda), a competing anti-PD-1 antibody, as first-line treatment in metastatic NSCLC patients whose tumors have high expression levels of the PD-L1 protein.
With these approvals, the stage was set to move these drugs into combination treatments that may increase their efficacy. Not surprisingly, combinations with chemotherapy have now been explored, among other possibilities. Continue reading…
“A combination of CMP-001, an intratumoral Toll-like receptor 9 (TLR9) agonist, and pembrolizumab (Keytruda), tested in patients with metastatic melanoma resistant to PD-1 checkpoint inhibition, was well tolerated and had clinical activity according to preliminary data presented from the ongoing phase Ib clinical trial at the AACR Annual Meeting 2018, April 14-18, in Chicago.
” ‘Checkpoint inhibition is quickly becoming a key tool for oncologists to treat cancer,’ said Mohammed Milhem, MBBS, clinical professor of internal medicine at the University of Iowa, Iowa City. ‘However, there are many patients that either initially respond to checkpoint inhibition and then progress, or never respond to this therapy to begin with. Finding safe and effective therapies for these patients is critical.’ ”
Drugs that activate the immune system to attack cancer in a process known as immune checkpoint blockade (ICB) are a focus of intense investigation. A number of them are already approved by the U.S. Food and Drug Administration (FDA) for various cancers; namely, the anti-CTLA4 antibody ipilimumab (Yervoy), two anti-PD-1 antibodies: pembrolizumab (Keytruda) and nivolumab (Opdivo), and three anti-PD-L1 drugs: atezolizumab (Tecentriq), avelumab (Bavencio) and durvalumab (Imfinzi). These ICB drugs have the potential to induce durable cancer regressions, but the majority of cancer patients just do not respond to them at all.
Biomarkers, signature molecules in the blood or other tissue, can sometimes be used to predict a patient’s response to a given treatment. But no reliable biomarkers exist for ICB, and this is a serious concern. Patients who may really benefit from ICB could be overlooked, and patients who are not likely to respond may receive useless (and very expensive) ICB treatment.
Most potential response predictors that have already been identified are not yet useful for one or all of the following reasons: they are not extensively validated, their significance is still uncertain and may differ from one cancer (or even one patient) to another, or they are technically challenging for routine use. These markers are addressed below. Continue reading…
“In a groundbreaking development, results from a recent clinical trial to treat lung cancer show that a novel immunotherapy combination is surprisingly effective at controlling the disease’s progression. The study, published April 4 in the journal The Lancet Oncology, focused on non-small cell lung cancer, which is the most common form of lung cancer.”
“Immunotherapy remains a viable option for pretreated patients with non-small cell lung cancer, but the data are rapidly evolving, according to a presenter at HemOnc Today New York.
” ‘We have come a long way with the development of checkpoint inhibitors, and we have to remember that they became famous and exerted their effect in the chemotherapy-refractory setting first,’ Benjamin Levy, MD, assistant professor of oncology at Johns Hopkins University and clinical director of Sidney Kimmel Cancer Center at Sibley Memorial Hospital in Washington, said during his presentation.”