The Growing Arsenal of Immunotherapy Drugs for Melanoma


Large numbers of immune cells (T cells in particular) are frequently found within or adjacent to melanoma tumors, indicating that the tumors attract the attention—if not the action—of the immune system. True to its reputation as one of the most ‘immunogenic‘ cancers, melanoma now has more U.S. Food and Drug Administration (FDA)-approved immunotherapy (immune system-targeting) drugs than any other cancer type. As a consequence, metastatic melanoma is no longer the universally fatal disease it was even just 3 or 4 years ago. Continue reading…


A Breast Cancer Tumor's Immune Signature Could Predict Response to Neoadjuvant Therapy

“In a study reported in the Journal of Clinical Oncology, Denkert et al found that increased tumor-infiltrating lymphocytes and the presence of lymphocyte-predominant breast cancer were associated with increased rates of pathologic complete response in patients receiving neoadjuvant anthracycline-taxane treatment with or without carboplatin. Higher rates were observed with carboplatin, with treatment interactions being significant among all patients and among those with HER2-positive disease but not among those with triple-negative disease. mRNA profiles for immune-related genes also distinguished pathologic complete response rates.

“The study involved 580 tumors from patients in the GeparSixto trial, which assessed the effects on pathologic complete response rates of adding carboplatin to neoadjuvant anthracycline plus taxane treatment. The current analysis assessed the effects on pathologic complete response of tumor-infiltrating lymphocyte levels, the presence of lymphocyte–predominant disease, and levels of immune-activating (CXCL9, CCL5, CD8A, CD80, CXCL13, IGKC, CD21) and immunosuppressive genes (IDO1, PD-1, PD-L1, CTLA4, FOXP3).”


Combining Radiation and Immune Therapies Could Be a Good Option for Melanoma Treatment

“Treating metastatic melanoma with a triple threat—including radiation therapy and two immunotherapies that target the CTLA4 and PD-1 pathways—could elicit an optimal response in more patients, one that will boost the immune system’s attack on the disease, suggests a new study from a multidisciplinary team of researchers from Penn’s Abramson Cancer Center published today in Nature.

“The study, led by senior authors Andy J. Minn, MD, PhD, assistant professor of Radiation Oncology, Robert Vonderheide, MD, DPhil, the Hanna Wise Professor in Cancer Research, Amit Maity, MD, PhD, professor of Radiation Oncology, and E. John Wherry, PhD, professor of Microbiology and director of the Institute for Immunology at the Perelman School of Medicine at the University of Pennsylvania, reports for the first time on the response and resistance to radiation combined with ipilimumab (an antibody against CTLA4) in both patients and mice.

“In the phase I clinical study, known as the ‘RadVax’ trial, the team found that combining ipilimumab with radiation was safe and shrank tumors in a subset of 22 metastatic melanoma patients (18 percent). The concurrent mouse study shed light on a mechanism of resistance, known as the PD-L1 pathway, found in many patients whose cancers progressed, suggesting that an antibody against PD-L1 or its partner PD-1 is an ideal third treatment to improve response and immunity.”


Immune System-Boosting Drugs, New and Old, Are Explored in Combination Treatments for Lung Cancer


Readers of this blog will already know a thing or two about immunotherapy (immune system-activating drugs) and targeted therapy in lung cancer. Both approaches have benefited many patients in recent years. Now, research is being done to combine immunotherapies with other types of drugs. Of particular interest are immunotherapies that target PD-1, PD-L1, and CTLA4. These drugs, also known as immune checkpoint antibodies, are being tested in combination with other drugs in patients participating in the clinical trials below. Continue reading…


UPDATE 1-Early Data Promising for AstraZeneca Cancer Drug Combination

The gist: Researchers found promising results for a new lung cancer treatment in a clinical trial—a research study with volunteer patients. The immunotherapy treatment combines the drugs MEDI4736 and tremelimumab. It is meant to boost a patient’s own immune system to fight cancer.

“Early results for a closely watched cancer drug combination from AstraZeneca that boosts the immune system show the cocktail is promising, though limited patient numbers mean the data is far from conclusive.

“The British drugmaker, which fended off a $118 billion takeover bid from Pfizer in May in part by talking up its cancer drug prospects, has high hopes for the combination of two experimental drugs known as MEDI4736 and tremelimumab.

“The company is still exploring a range of doses, so testing of the drugs in lung cancer is taking time to yield results and data on only two dozen patients was reported at the European Society for Medical Oncology (ESMO) congress on Saturday.

“Chief Executive Pascal Soriot had said earlier this month that the ESMO numbers would be limited.

“Still, researcher Scott Antonia of the Moffitt Cancer Center in Florida said the early signals were encouraging, both for safety and efficacy. ‘It looks very, very promising, he said.

“AstraZeneca expects to have more definitive results later this year and also plans to start a pivotal clinical trial with the combination either late this year or at the start of 2015.”


Immune System-Boosting Treatments Show Long-Sought Successes for Lung Cancer Patients


In the past 2 years, cancer treatments known as immune therapies have become all the rage. However, they have actually been explored for decades, particularly in melanoma, and have produced some notable successes. Now, immune therapies are showing more and more promise for lung cancer. Continue reading…


Engaging the Immune System May Be a Useful Strategy in SCLC

Drugs that enhance the body’s immune response (immunotherapies) may help patients with small cell lung cancer (SCLC). Immunotherapy may be beneficial on its own, but could also complement standard chemotherapy. An overview of recent studies and ongoing clinical trials highlighted several promising immunotherapies, including ipilimumab (Yervoy). Yervoy, which has been approved to treat certain kinds of skin cancer, targets a protein called CTLA4, which acts as an “off switch” on immune system cells. By deactivating CTLA4, Yervoy allows the immune system to continue attacking tumors. Another immune treatment that may be combined with traditional chemotherapy is interferon-alpha, a molecule that stimulates the body’s immune cells.