Immune and Targeted Therapies Combined with Radiation Therapy Improves Outcomes for Melanoma Brain Metastases Patients, Say Moffitt Researchers

Excerpt:

“Brain metastases are one of the most common complications of advanced melanoma, requiring multidisciplinary management. Patients who are diagnosed with these metastases have an expected median survival of only 4 to 5 months. Moffitt Cancer Center researchers hope to improve these survival rates following a new study in Annals of Oncology that shows novel immune and targeted therapies with radiation therapy improves the outcomes of patients with melanoma brain metastases over conventional chemotherapy.”

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Gene Defect as a Potential Gateway for Targeted Prostate Cancer Therapy

Excerpt:

“The loss of CHD1, one of the most frequently mutated genes in prostate tumors, sensitizes human prostate cancer cells to different drugs, including PARP inhibitors. This suggests CHD1 as a potential biomarker for targeted prostate cancer therapy. These are the results of a study published in EMBO Reports.

“A team of researchers in Germany and Denmark led by Steven Johnsen, Professor at the University Medical Center Göttingen, Germany, used human prostate cancer cell lines and depleted them of the DNA-binding protein CHD1. The CHD1 gene is mutated in 15-27% of all prostate tumors, and such mutations correlate with chromosomal instability and poor prognosis for prostate cancer patients. The researchers could demonstrate that CHD1-depleted cells have defects in homologous recombination (HR), an important mechanism for repairing breaks in the DNA molecule. The data indicate that CHD1’s normal function is the loosening of DNA around break sites in order to facilitate the access of HR repair proteins. Importantly, like cancer cells with other mutations in the HR repair pathway, CHD1-depleted prostate cancer cells proved to be hypersensitive to chemotherapeutic drugs causing DNA breaks, such as Mitomycin C, Irinotecan and PARP inhibitors.”

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Melanoma: New Drugs and New Challenges (Part 2 of 2)


Editor’s note: This is part 2 of a 2-part post on the latest research in melanoma. To learn about research into drug combinations for melanoma that may work better than single drugs, check out Melanoma: New Drugs and New Challenges (Part 1 of 2).

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…


Targeted Therapies Beneficial in KRAS-Mutated NSCLC

Excerpt:

“Targeted therapies that do not contain erlotinib can be beneficial for patients with KRAS-mutated (KRAS mut+) advanced non-small-cell lung cancer (NSCLC), according to a study published online Aug. 1 in the Journal of Clinical Oncology.

“Vassiliki Papadimitrakopoulou, M.D., from the University of Texas MD Anderson Cancer Center in Houston, and colleagues examined the effects of targeted therapies in NSCLC. Patients were randomized to four arms: erlotinib (22 patients), erlotinib plus MK-2206 (42 patients), MK-2206 plus AZD6244 (75 patients), or sorafenib (61 patients).

“The researchers found that the primary end point of an eight-week disease control rate (DCR) was 48 percent in all 186 evaluable patients (32, 50, 53, and 46 percent, respectively, for the four treatment arms). For the 27 percent of patients who were KRAS mut+, DCR was 20, 25, 62, and 44 percent, respectively, compared with 36, 57, 49, and 47 percent, respectively, for KRAS wild-type patients. Median progression-free survival was 2.0 months: 1.8 and 2.5 months for arms 1/2 and 3/4, respectively, in KRAS mut+ patients (P = 0.04). In KRAS wild-type patients, median overall survival was 6.5 months: 9.0 and 5.1 months in arms 1/2 and 3/4, respectively (P = 0.03).”

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Oxnard Explains Role of BRAF in NSCLC

Excerpt:

“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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Distinct Features Associated With Benefit for BRAF/MEK Inhibition

Excerpt:

“With the development of novel targeted and immunotherapeutic agents that are more efficacious than traditional chemotherapy, treatment paradigms in melanoma have undergone major changes. Current recommendations for first-line systemic therapy for patients with advanced or metastatic melanoma consider BRAF mutation status, tumor growth rate, and the presence or absence of cancer-related symptoms.

“Immunotherapies with agents that block CTLA-4 or PD-1/PD-L1 checkpoints have been associated with durable responses in a subset of patients, and are often considered for patients with low-volume, asymptomatic metastatic melanoma. Targeted therapies, on the other side, are preferred for patients with BRAF-mutant tumors who have symptomatic disease and benefit from the rapid response associated with these agents.”

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Clinical Trial Versus Standard Protocol: Why and How to Enroll in a Trial


My job at Cancer Commons is to help cancer patients better understand and make decisions about their treatment. Through our Ask Cancer Commons service, I also strive to inform patients about new drugs in trials that they can discuss with their oncologists. Sometimes, I explain the rationale behind a patient’s current or upcoming treatment, and sometimes I try to convince patients to actually get treated, rather than hope that a vegetarian diet and herbal supplements will cure their metastatic disease. Continue reading…


First-Line Osimertinib Yields Nearly 80% Response in Advanced Lung Cancer

Excerpt:

“First-line osimertinib, a targeted therapy against EGFR mutations, was found to be effective in patients with advanced non–small-cell lung cancer (NSCLC), resulting in a 77% overall response rate, according to the results of recent study. In addition, the treatment-naive patients in the study achieved a median progression-free survival of 19.3 months.

“The data from two phase I expansion cohorts were presented by Suresh Ramalingam, MD, professor of hematology and medical oncology at Emory School of Medicine and deputy director of the Winship Cancer Institute in Atlanta, at the European Lung Cancer Conference 2016 in Geneva (LBA 1_PR).”

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Steroid Use With Abiraterone Offers Multidimensional Benefits to Patients With mCRPC

Excerpt:

“For decades, the standard of care for men with advanced prostate cancer has been the depletion or inhibition of androgens. While androgen-deprivation therapy (ADT) often results in temporary tumor regression or symptom relief in some patients, disease progression ultimately occurs over time. For patients with metastatic disease, the median overall survival (OS), until very recently, had been less than 2 years after chemotherapy.

“While tumor progression with ADT was previously believed to be hormone-refractory or androgen-independent, a large body of evidence supports that metastatic castration-resistant prostate cancer (mCRPC) is commonly driven by elevated steroid synthesis, increased expression or splice variants of the androgen receptor (AR), or AR ligand promiscuity, indicating the ongoing need for targeted androgen therapies.”

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