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…
“Back-to-back discoveries from Cleveland Clinic demonstrate for the first time how a testosterone-related genetic abnormality can help predict individual patient responses to specific prostate cancer therapies.
“The studies, published in the October 12 issue of JAMA Oncology, suggest that men who inherit this variant would benefit from a personalized treatment plan that targets specific hormonal pathways.”
University of Colorado Cancer Center | Sep 6, 2017
“For many years, oncologists have known that cancers can secrete complex molecules into the blood and that levels of these molecules can be easily measured. These so-called ‘tumor markers’ are traditionally associated with a single dominant cancer type, for example Prostate Specific Antigen (PSA) linked to prostate cancer, Carcinoembryonic antigen (CEA) to colorectal cancer, CA125 to ovarian cancer, CA19.9 to pancreatic cancer and CA27.29 to breast cancer. However, the real challenge has been to determine a practical use for these markers. They don’t appear to be useful as a means of screening otherwise healthy people for evidence of underlying cancers.”
“New research shows that taking molecular variables into account will improve the prognostic classification of the lethal brain cancer called glioblastoma (GBM).
“The study was led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).
“Published in the journal JAMA Oncology, the study found that adding significant molecular biomarkers to the existing GBM classification system improves the prognostic classification of GBM patients who have been treated with radiation and the drug temozolomide.”
“Prostate cancer (PC) is the second leading cause of male cancer death in the United States with an estimated 26,000 deaths in 2016. Two-thirds of all PC deaths observed in the US are men with localized disease who developed metastasis. Several markers for dying from prostate cancer exist, but whether these are markers for telling who is likely to die early from any cause, and how their performance compares, is unknown. Identifying such a marker is important because we can then identify which men may benefit from new, more aggressive treatments for prostate cancer.”
“Checkpoint blockade has been a revolutionary advance in cancer treatment, supported by extensive pre-clinical and phase II/III clinical data. Recent long-term survival data suggest that immunotherapy may actually be curing some patients with advanced melanoma. In addition, potential biomarkers may help select the best immunotherapy for each patient.”
“Geoffrey R. Oxnard, MD, specializes in researching molecular mutations in non–small cell lung cancer (NSCLC) with a particular emphasis on prognostic and predictive biomarkers. Oxnard, who is an assistant professor of Medicine at Harvard Medical School and a thoracic oncologist at the Dana-Farber Cancer Institute, spoke with Targeted Oncology about the potential for BRAF-targeting therapies in NSCLC.
“TARGETED ONCOLOGY: What is the potential for utilizing currently available BRAF/MEK-targeted therapies in treating patients with NSCLC?
“Oxnard: Combination BRAF/MEK inhibitor therapy is a very compelling approach because combinations of BRAF and MEK inhibitors have clearly been shown to improve response rates and overall survival in melanomas harboring BRAF V600E mutations when compared with single-agent BRAF inhibition.”
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“The American Society of Clinical Oncology (ASCO) today issued a new clinical practice guideline for women with early-stage invasive breast cancer and known hormone receptor and human epidermal growth factor 2 (HER2) receptor status. The guideline includes evidence-based recommendations on the appropriate use of breast tumor biomarker tests to guide decisions on adjuvant systemic therapy.
” ‘In the era of precision medicine, the role of biomarkers in guiding clinical care is greater than in the past. An extensive number of new tests have come out in the last 5-10 years, but not all have sufficient evidence of clinical utility,’ said Lyndsay N. Harris, MD, co-chair of the ASCO expert panel that developed the guideline. ‘These latest recommendations truly inform physicians about which tests need to be performed. But this is not all that goes into patient care—doctors need to continue discussions with patients to develop individualized treatment plans.’ “
“Although nivolumab (Opdivo) and ipilimumab (Yervoy) together demonstrate superior survival in previously untreated patients with advanced melanoma, the combination comes with additional toxicity and an increased price tag, says Jason Luke, MD, assistant professor of Medicine at the University of Chicago Medicine.
“ ‘There have been several studies designed around trying to predict which patients are most likely to benefit from anti–PD-1 or immunotherapy combinations. I really think that is going to be an essential part of the future approach to treatment, says Luke. ‘Not all patients respond to these treatments. There are additional toxicities with the combinations, and there are also cost issues because of how catastrophically expensive these drugs are. We really need to know which patients are most likely to respond and which aren’t.’ “