Cancer Mutation Gains Ground as Test for Immunotherapy Drugs

Excerpt:

“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.”

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Physicians’ Misunderstanding of Genetic Test Results May Hamper Mastectomy Decisions

Excerpt:

“A recent survey of over 2,000 women newly diagnosed with breast cancer found that half of those who undergo bilateral mastectomy after genetic testing don’t actually have mutations known to confer increased risk of additional cancers, according to a study by researchers at the Stanford University School of Medicine and four other U.S. medical centers.

“Instead the women had what are known as variants of uncertain significance, or VUS, that are often eventually found to be harmless. A bilateral mastectomy is a surgical procedure in which both of a woman’s breasts are removed after a diagnosis of in one breast.”

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Genome Analysis Helps Keep Deadly Brain Cancer at Bay for Five Years

Excerpt:

“An analysis of a patient’s deadly brain tumor helped doctors at Smilow Cancer Hospital identify new emerging mutations and keep a 55-year old woman alive for more than five years, researchers report in the journal Genome Medicine.

“The median survival rate for patients with glioblastoma multiform (GBM) is only 15 months, but three separate genomic analyses of the tumor identified new mutations that allowed doctors to adjust treatment and keep the patient alive for over five years, through two recurrences of the cancer.”

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Targeted Treatment May Be Feasible in Pediatric Brain Tumors

Excerpt:

“Results from a large clinical study showed that testing pediatric brain tumors for genetic abnormalities is feasible and could play a role in guiding patients’ treatment.

“The study, published in Neuro-Oncology, showed that more than half of the samples taken from pediatric brain tumors and analyzed using genomic profiling had genetic irregularities that could influence how the disease was diagnosed or treated with approved drugs or agents being evaluated in clinical trials.”

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Testing for Tumor Mutations: Liquid Biopsy Versus Traditional Biopsy


Liquid biopsies, virtually unknown even a year or two ago, are becoming common tools in precision diagnostics for cancer. Here, I will try to explain some of the more important differences between liquid and “traditional” tumor biopsies.

Biopsies of solid tumors (e.g., lung, breast, or brain tumors) involve surgically removing a small part of a tumor and sending it to pathology lab. In the last few years, doctors have also started to send some tumor samples to special service labs that analyze tumor DNA for the presence of cancer-related mutations.

By definition, regular biopsies can be intrusive and are sometimes associated with side effects, such as bleeding or infection. However, they provide some really essential information; i.e., the histology and grade of the tumor and other tumor characteristics necessary to determine the best choice of treatment. For lung cancer, for example, a biopsy determines the type of tumor—adenocarcinoma, squamous cancer, small-cell lung cancer, or another, less common type. For breast cancer, a routine test will determine if the tumor expresses estrogen, progesterone receptors, and a protein called HER2. These tests are critically important in guiding treatment choices. If mutational analysis of cancer-related genes is also performed (which doesn’t always happen, unfortunately), it may guide treatment with targeted drugs. Continue reading…


Case for Liquid Biopsies Builds in Advanced Lung Cancer

Excerpt:

“For patients with advanced lung cancer, a non-invasive liquid biopsy may be a more effective and suitable alternative to the gold standard tissue biopsy to detect clinically relevant mutations and help guide their course of treatment, suggests a new study published this week in the journal Clinical Cancer Research from researchers at the Abramson Cancer Center at the University of Pennsylvania(ACC).

“In patients with advanced non-small cell lung cancer (NSCLC) treated at Penn’s ACC, mutations detected from liquid biopsies (cell-free circulating tumor DNA (ctDNA) captured from blood) closely paralleled the mutations from tissue biopsies identified in next generation sequencing tests: EGRF, TP53, and ALK, to name a few. What’s more, in several cases, liquid biopsies captured clinically relevant mutations not found in tissue biopsies as patients’ disease progressed.”

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More Cancer Mutations May Be Good for Immunotherapy Patients

Excerpt:

“Mark Perkins considers himself a poster child for the new generation of cancer drugs that harness the patient’s immune system to attack sick cells. Two years after trying Merck & Co.’s Keytruda — and almost four years after receiving a prognosis of as little as six months left to live — he is cancer free.

“The 56-year-old grandfather’s case is more than a success story for a new class of treatments that have fewer side effects than standard chemotherapy. It’s also at the frontier of what could possibly lead to a new approach to treating cancer, if it turns out that patients who, like Perkins, have many more mutations in their tumors than the average have a better chance of responding to immunotherapy.

“Drugs like Keytruda, known as checkpoint inhibitors, have produced dramatic responses in some advanced cancer patients, but doctors still don’t understand why only about 20 percent gain long-term survival. Researchers say looking at the mutation load for answers makes scientific sense, because these drugs work by taking the brakes off the immune system’s killer T-cells, unleashing them to go after cancerous cells. In theory, the more mutations a cancer has, the more foreign it will appear to the newly enhanced immune cells.”

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New RAF-targeted Therapeutic Shows Early Promise Against Tumors With BRAF and RAS Mutations

Excerpt:

“The new investigational anticancer therapeutic BGB-283, which targets the RAF family of proteins, was safe, tolerable, and showed signs of clinical activity in patients who had a range of types of cancer with mutations in BRAF, KRAS, and NRAS, according to results from a phase I clinical trial presented here at the AACR Annual Meeting 2016, April 16-20.

“ ‘BRAF gene mutations fuel cancer cell proliferation and survival in a number of types of cancer, including melanoma, and thyroid and colorectal cancers,’ said Jayesh Desai, FRACP, a medical oncologist at The Royal Melbourne Hospital in Melbourne, Australia. ‘In melanoma, the BRAF V600E mutation predominates, and specific inhibitors of the BRAF V600E mutant protein have been approved for treating patients with melanoma with BRAF V600E gene mutations.’ ”

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Novel Entrectinib Trial Focuses on Gene Rearrangements Across Many Tumor Types

Excerpt:

“A decade ago, researchers believed molecular alterations occurred in only one or two cancer types. That way of thinking has changed, however, with the understanding that the same alterations, especially gene fusions, can occur across many different tumor types.

“As a result, researchers have designed a recently launched clinical study into entrectinib, a first-inclass inhibitor of tropomyosin receptor kinases (Trk), as a basket trial in which the drug can be evaluated simultaneously for activity against three gene alterations and multiple tumor types.

“STARTRK-2 (NCT02568267) is an open-label, phase II study in which patients with locally advanced or metastatic solid tumors are assigned to different baskets according to whether their tumors harbor rearrangements in one of three key genes—NTRK1/2/3, ROS1, or ALK.”

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