“Inovio Pharmaceuticals, Inc. (NASDAQ:INO) today initiated a phase 1b/2a immuno-oncology trial in patients with newly diagnosed glioblastoma (GBM) designed to evaluate cemiplimab (also known as REGN2810), a PD-1 inhibitor developed by Regeneron Pharmaceuticals, Inc.(NASDAQ:REGN), in combination with Inovio’s INO-5401 T cell activating immunotherapy encoding multiple antigens and INO-9012, an immune activator encoding IL-12.”
“While immunotherapy with programmed death receptor 1 (PD-1) inhibiting antibodies has revolutionized the treatment of non-small cell lung cancer (NSCLC), use of these agents comes at the cost of potential serious immune-related adverse events (irAEs). In melanoma, development of cutaneous irAEs, such as rash and vitiligo, during treatment with PD-1 inhibitors has been shown to be associated with survival benefit, suggesting that early onset of irAEs may predict treatment outcomes. However, in NSCLC, the predictive value of immunotherapy-related toxicity as a clinical marker for efficacy to PD-1 inhibition is unknown. A multi-institution retrospective study investigated the relation between the development of irAEs and efficacy of PD-1 inhibitors in 134 patients with advanced or recurrent NSCLC who received second-line treatment with nivolumab. The primary outcome for this analysis was progression-free survival (PFS) according to the development of irAEs in a 6-week landmark analysis.”
“Immunotherapy has led a transformation for melanoma care but combinations of anti–PD-1 and CTLA-4 agents are toxic and biomarkers are not available to help personalized treatment, calling for further research into less toxic and more effective options, according to a presentation by Caroline Robert, MD, PhD, at the 2017 World Congress of Melanoma.
“At this point, the only approved immunotherapy combination remains the PD-1 inhibitor nivolumab (Opdivo) and the CTLA-4 inhibitor ipilimumab (Yervoy). However, research into combination approaches is now focusing on triplets of anti–PD-1 therapies and new checkpoints, such as IDO. Additionally, ongoing research continues to search of a biomarker of response for immunotherapy in melanoma.”
“In a first-of-its-kind study, University of California San Diego School of Medicine researchers report that a blood sample, or liquid biopsy, can reveal which patients will respond to checkpoint inhibitor-based immunotherapies.
” ‘We can help predict response to immunotherapy by measuring the number of mutations in circulating tumor DNA using a simple blood test,’ said Yulian Khagi, MD, UC San Diego Moores Cancer Center fellow and first author. ‘Immunotherapy can result in serious side effects, and therefore being able to predict who will respond is important to mitigating potential risk to each patient.’ ”
American Society for Radiation Oncology | Sep 24, 2017
“A new study involving patients with stage IV cancer finds that treatment with radiation therapy and immunotherapy can halt the growth of tumors by stimulating the body’s immune system to attack the cancer. In the phase II trial, patients with end-stage cancer that had spread to the lungs or liver demonstrated a favorable response to the combined treatment. Between 30 and 60 percent of the patients, depending on the treatment arm, found that their cancer stopped spreading. Findings will be presented today at the 59th Annual Meeting of the American Society for Radiation Oncology (ASTRO).”
Non-metastatic breast cancers are most often treated with surgery, but if the tumors are fairly large, or involve nearby lymph nodes, neoadjuvant (pre-operative) treatments with chemotherapy (NAC) are done first. NAC often reduces the tumor size and kills cancer cells in lymph nodes, if present, prior to surgery, improving the outcome. The best possible result of neoadjuvant treatment is pCR (pathologic compete response), when the tumor is no longer visible in imaging studies. Here, I review the new directions in which neoadjuvant treatments are evolving.
Today, treatments for metastatic breast cancers are tailored for specific subtypes. Starting with the introduction of the drug trastuzumab (Herceptin) for HER2-positive cancers, new, more specific treatment options were eventually developed and approved for other types as well. Estrogen deprivation endocrine therapies, lately prescribed in combination with CDK4/6 inhibitors, are used in estrogen receptor (ER)-positive cancers. Triple negative cancers (TNBC) are still treated mostly with chemotherapy, but immune checkpoint drugs and PARP inhibitors are explored in clinical trials, with some successes reported.
However, neoadjuvant treatments (except for HER2+ cancers) remain largely limited to chemotherapy regimens. This is starting to change now, with new approaches tailored to the cancer type being investigated in clinical trials.
In this regard, it is important to mention the I-SPY2 trial, NCT01042379, which started in 2010 and is for women with stage II-III breast cancer. It offers about a dozen drugs that are chosen based on particular features of the newly diagnosed cancers. This trial has a unique design and has produced some important results. Additional treatments and trials for various types of breast cancer are discussed below. Continue reading…
“The jackpot cancer immunotherapy ambitions of AstraZeneca stumbled in July with the failure of a closely watched clinical trial in newly diagnosed lung cancer. Friday, the Anglo-Swedish drugmaker attempts a recovery with positive results from a new study, also in lung cancer, but aimed at a niche group of patients.
“AstraZeneca still trails cancer immunotherapy leaders Merck and Bristol-Myers Squibb, but staking a claim in lung cancer marks progress.”
“In a head-to-head comparison of two immunotherapy drugs used to prevent relapse in certain patients with advanced melanoma, one treatment was the clear winner — and it’s not the one that most people get.
“The international study, released Sunday, involved 900 patients whose tumors were removed by surgery but who remained at high risk of recurrence of melanoma, an often aggressive form of skin cancer.”
“Scientists are stepping up the hunt for better diagnostic tests to predict if cancer patients will benefit from costly modern immunotherapy drugs, which are transforming cancer care but remain a hit-and-miss affair.
“Research presented at Europe’s biggest oncology congress in Madrid adds to evidence that patients with an above average number of genetic mutations in their tumors have a better chance of responding to the new treatments, and drugmakers are racing to confirm the idea.”