“Attacking an aggressive brain tumor with immunostimulatory gene therapy while enhancing the immune system’s ability to fight it with immune checkpoint inhibitors might be a promising approach to treat patients with glioblastoma multiforme, a brain tumor currently associated with a very poor prognosis.
“Results of an initial study of tumors from patients with lung cancer or head and neck cancer suggest that the widespread acquired resistance to immunotherapy drugs known as checkpoint inhibitors may be due to the elimination of certain genetic mutations needed to enable the immune system to recognize and attack malignant cells. The study, conducted by researchers on the cells of five of their patients treated at the Johns Hopkins Kimmel Cancer Center, is described online Dec. 28 in Cancer Discovery.”
“G1 Therapeutics, Inc., a clinical-stage oncology company, announced today a clinical trial collaboration with Genentech, a member of the Roche Group. A Phase 2 clinical trial is expected to begin in the first half of 2017 and will evaluate the combination of Genentech’s immune checkpoint, anti-PD-L1 antibody Tecentriq® (atezolizumab) with G1’s CDK4/6 inhibitor trilaciclib (G1T28) as a first-line treatment for patients with small-cell lung cancer (SCLC) receiving chemotherapy.”
“Based on encouraging efficacy signals and safety data from separate trials exploring the PD-1 inhibitor pembrolizumab (Keytruda) and the PD-L1 inhibitor durvalumab (MEDI4736), there is a role for checkpoint inhibitors in the treatment of glioblastoma multiforme (GBM). Data from the studies were reported by David Reardon, MD, at the 21st Society for Neuro-Oncology (SNO) Annual Scientific Meeting.
“Reardon said that these results mark important firsts in the field: ‘There has been a lot of anticipation regarding the role of checkpoint inhibitors for glioblastoma and whether we’ll see results in any way similar to the exciting results that have been observed in other cancer indications with this new class of cancer therapeutics.’ ”
Last year, the U.S. Food and Drug Administration (FDA) approved two anti-PD-1 checkpoint inhibitors, a type of immunotherapy, for treatment of non-small cell lung cancer (NSCLC) in patients whose cancer has progressed after first-line treatment with chemotherapy. Now, the manufacturers of both drugs, pembrolizumab (made by Merck) and nivolumab (made by Bristol-Myers Squibb; BMS) are intent on expanding the indications for use of their drugs. To this end, they have conducted clinical trials testing each as a first-line treatment (i.e., in previously untreated patients), comparing them to standard chemotherapy. Continue reading…
“The first phase III study of PD-L1 inhibitor atezolizumab in previously-treated non-small-cell lung cancer has seen significant improvements in survival compared to standard chemotherapy, researchers reported at the ESMO 2016 Congress in Copenhagen.
“PD-L1 inhibitors are of a class of cancer immunotherapies called checkpoint inhibitors, and work by inhibiting one of the mechanisms of resistance developed by cancer cells in order to evade the immune system.”
“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.”
“A collaboration between an immunologist helping his stepmother fight cancer and the oncologist who treated her led to a discovery that could help many more patients benefit from a transformative new therapy.
“A new class of drugs called checkpoint inhibitors works by releasing a molecular brake that stops the immune system from attacking tumors. So-called immunotherapy has been approved for several types of cancers and found to extend lives of patients with advanced disease for many years. The problem is that for most patients immunotherapy doesn’t work.
“The researchers, from University of California, San Francisco, said they identified a unique type of immune-system cell that ‘robustly’ predicts whether patients will respond to one of the medicines—an achievement has the potential to significantly expand the number of cancer patients who benefit from checkpoint inhibitors.”
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As always, the more new treatments become available in melanoma, the more new challenges arise. With eight new drugs approved for melanoma in the last five years, oncologists may sometimes face the difficult choice of what drugs to choose for a patient’s first-line treatment. Immune checkpoint drugs sometimes cause serious side effects, but progress is being made on how to treat these and also how to treat patients with pre-existing autoimmune conditions. New approaches are needed in efforts to prevent recurrence of melanomas diagnosed at earlier stages of disease progression. These and other challenges are discussed below. Continue reading…