Immune Analysis of On-Treatment Longitudinal Biopsies Predicts Response to Melanoma Immunotherapy

Excerpt:

“Immune response measured in tumor biopsies during the course of early treatment predicts which melanoma patients will benefit from specific immune checkpoint blockade drugs, researchers at The University of Texas MD Anderson Cancer Center report in the journal Cancer Discovery.

“Analysis of biopsies before treatment did not indicate who would respond in this unique longitudinal study of 53 melanoma patients treated with two immune checkpoint inhibitors between October 2011 and March 2015.

” ‘Before treatment, analyzing samples with a 12-marker immune panel or a 795-gene expression panel, you can’t tell who will respond with any degree of certainty. On treatment, there were night-and-day differences between responders and non-responders,’ said study senior author Jennifer Wargo, M.D., associate professor of Genomic Medicine and Surgical Oncology.”

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What Is Immunotherapy? The Basics on These Cancer Treatments

Excerpt:

“Some of the most promising advances in cancer research in recent years involve treatments known as immunotherapy. These advances are spurring billions of dollars in investment by drug companies, and are leading to hundreds of clinical trials. Here are answers to some basic questions about this complex and rapidly evolving field.

“Immunotherapy refers to any treatment that uses the immune system to fight diseases, including cancer. Unlike chemotherapy, which kills cancer cells, immunotherapy acts on the cells of the immune system, to help them attack the cancer.

“Drugs called checkpoint inhibitors are the most widely used form of immunotherapy for cancer. They block a mechanism that cancer cells use to shut down the immune system. This frees killer T-cells — a critically important part of the immune system — to attack the tumor. Four checkpoint inhibitors have been approved by the Food and Drug Administration and are on the market. They are given intravenously.”

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Harnessing the Immune System to Fight Cancer

Excerpt:

“Steve Cara expected to sail through the routine medical tests required to increase his life insurance in October 2014. But the results were devastating. He had lung cancer, at age 53. It had begun to spread, and doctors told him it was inoperable.

“A few years ago, they would have suggested chemotherapy. Instead, his oncologist, Dr. Matthew D. Hellmann of Memorial Sloan Kettering Cancer Center in New York, recommended an experimental treatment: immunotherapy. Rather than attacking the cancer directly, as chemo does, immunotherapy tries to rally the patient’s own immune system to fight the disease.

“Uncertain, Mr. Cara sought a second opinion. A doctor at another major hospital read his scans and pathology report, then asked what Dr. Hellmann had advised. When the doctor heard the answer, Mr. Cara recalled, ‘he closed up the folder, handed it back to me and said, ‘Run back there as fast as you can.’ ”

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Melanoma Tx Tied to Neurologic Disorder

Excerpt:

“Researchers reported two cases of demyelinating polyradiculoneuropathy after treatment with pembrolizumab (Keytruda) for advanced melanoma.

“The report, in a letter published Wednesday in the New England Journal of Medicine, raises concerns about serious, perhaps irreversible, and previously unknown adverse effects from this class of drug, which targets the PD-1 immune checkpoint pathway. These immunotherapies, offering a whole new way of attacking cancer, have generated excitement across the oncology community in recent years.

“The first patient was receiving treatment for recurrent nasal-cavity melanoma, and developed symptoms consistent with Guillain-Barré syndrome 8 weeks after beginning pembrolizumab therapy (2 mg/kg every 3 weeks), according to Philippe Saiag, MD, PhD, of Versailles Saint-Quentin-en-Yvelines University in Versailles, France, and colleagues.”

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I Thought Melanoma Would Kill Me. Here's Why It Didn't.

Excerpt:

“Several months ago, my wife, Françoise, and I attended something novel for melanoma patients: a survivors’ dinner. People said they wanted to make it an annual gathering. Planning anything that far in advance had been pointless for me. Two years ago, I was about to accept hospice care.

“When I was diagnosed in 1996, very early surgery was the only reliably successful treatment. A more advanced case was essentially a death sentence. Over the past five years, a series of revolutionary drugs have given me and many other people a surprisingly hopeful prospect. Nevertheless, the drugs’ development process has often been excruciating for participants in clinical trials, and the drugs’ remarkably high costs limit their value.”

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First-Line Nivolumab Could Be Good Option in Lung Cancer

Excerpt:

“Two parts of a phase I trial found that nivolumab could be a good first-line treatment option for patients with advanced non–small-cell lung cancer (NSCLC). In one part of the study, the immunotherapy agent yielded good safety results and durable responses as monotherapy, and in the other, nivolumab combined with platinum-based doublet chemotherapy had more toxicity but again good responses.

“Currently, platinum-based doublet chemotherapy (PT-DC) is the standard of care as a first-line therapy for NSCLC that is not driven by an EGFR or ALK mutation or rearrangement.

“ ‘Immune checkpoint inhibitors represent a distinct approach to treating malignancies, with durable antitumor activity and the potential for long-term survival demonstrated in multiple tumor types, including NSCLC,’ wrote Scott Gettinger, MD, of Yale Cancer Center in New Haven, Connecticut, and co-authors of the monotherapy study.”

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Merck Extends Cancer Immunotherapy Reach to First-Line Lung Cancer

Excerpt:

“Merck’s (MRK) flagship cancer immunotherapy Keytruda delayed the re-growth of tumors and prolonged survival in patients with newly diagnosed non-small cell lung cancer compared to chemotherapy, the company said Thursday.

“The new phase III study results from Merck are significant because they represent the first time that a drug belonging to the so-called checkpoint inhibitor class of cancer immunotherapies has demonstrated superiority over standard of care in the treatment of first-line lung cancer patients.

“Lung cancer is the most prevalent cancer globally, with more than 200,000 patients in the U.S. and 1.5 million patients globally diagnosed each year. As such, lung cancer is an important commercial market for the drug companies developing new therapies which harness the immune system to target and kill cancer cells.”

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Lung Cancer Highlights from ASCO 2016


This year, the Annual Meeting of the American Society of Clinical Oncology (ASCO) did not produce any truly groundbreaking revelations about new treatments for lung cancer. However, researchers did report quite a few positive findings, and some disappointing ones. I have summarized some of the more prominent presentations below. Continue reading…


Combining BRAF Inhibition, Anti-PD-1 No Help in BRAF-Mutant Melanoma

Excerpt:

“Patients with BRAF-mutant melanoma obtained no survival benefit from combined treatment of anti-BRAF therapy and an immune checkpoint inhibitor, a retrospective analysis showed.

“Median progression-free survival (PFS) was 6.0 to 6.5 months in BRAF-inhibitor naive patients who received a PD-1/PD-L1 inhibitor alone or with a BRAF inhibitor. Patients with prior exposure to a BRAF inhibitor had a median PFS of 8.0 months with anti–PD-1 therapy and 4.5 months with combined treatment. Median overall survival was 10.5 to 12 months with a PD-1/PD-L1 inhibitor alone or in combination with a BRAF inhibitor, regardless of prior BRAF inhibitor exposure status.

“ ‘BRAF inhibitor-refractory patients derived no additional benefit with anti-PD therapy in combination with BRAF inhibition,’ Wen-Jen Hwu, MD, of MD Anderson Cancer Center in Houston, and colleagues concluded in a poster presentation at the 2016 ASCO Annual Meeting in Chicago. ‘Clinical findings are similar with either anti-PD alone or in combination with BRAF inhibition in terms of objective response rate (ORR), disease control rate (DCR), and overall survival (OS).’ ”

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