Detection of PD-L1 in cell surface vimentin positive circulating tumor cells is associated with poor survival in cancer patients

UT MD Anderson Cancer Center, Houston, TX.

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA

Abstract 1596

Circulating tumor cells (CTCs) are the cells that detach from the primary tumor of patients and enter in to the blood stream and these can be represented as the seeds of metastasis. Increasing evidence has shown the detection of circulating tumor cells (CTCs) from blood of cancer patients parallels with tumor burden and is associated with poor prognosis. Although CTC counts change indicates a good modality to detect therapeutic response to drug treatments, there is an increasing need of a reliable marker that can be used to predict survival in cancer patients. One of the most prevalent markers detected in cancer patients is the cell surface glycoprotein called PD-L1 (also called B7-H1 and CD274). Aberrant expression of PD-L1 has been reported in several cancer types. Here in this study we tested the hypothesis that detection of PD-L1 in CTCs is associated with poor prognosis. To validate the hypothesis, we isolated cell-surface vimentin (CSV) positive CTCs from colorectal cancer patients using 84-1 method and analyzed for PD-L1 expression. Our results indicated that PD-L1 detection in CTCs was associated with poor overall survival (HR, 2.43; 95% CI, 1.11 to 5.35; p, 0.0264) in colorectal cancer patients undergoing treatment. These findings thus suggest that PD-L1 detection in CSV CTC could serve as a new prognostic tool. We further extend our observations in other types of cancers including breast, prostate and sarcoma. 

Citation Format: Arun Satelli, Zachary Brownlee, Hyangsoon Noh, Qing H. Meng, Scott Kopetz, Michael Overman, Shulin Li. Detection of PD-L1 in cell surface vimentin positive circulating tumor cells is associated with poor survival in cancer patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1596. doi:10.1158/1538-7445.AM2015-1596 

• ©2015 American Association for Cancer Research.

IMBRUVICA® (ibrutinib) Phase 3 RAY Data Show Significant Improvements in Progression-Free Survival Versus Temsirolimus in Patients with Relapsed or Refractory Mantle Cell Lymphoma

ORLANDO, Fla. and HORSHAM, Pa., Dec. 7, 2015 /PRNewswire/ -- Data from the Phase 3 RAY (MCL3001) study, an investigational clinical trial, showed oral IMBRUVICA^® (ibrutinib) significantly improved progression-free survival (PFS; the primary endpoint) versus intravenous temsirolimus in patients with relapsed or refractory mantle cell lymphoma (MCL). Janssen Biotech, Inc. announced IMBRUVICA was associated with a 57 percent reduction in the risk of disease progression or death with a median follow-up of 20 months. These data were published online in The Lancet today and presented in an oral session at the 2015 American Society of Hematology (ASH) meeting in Orlando, FL. IMBRUVICA is jointly developed and commercialized by Janssen and Pharmacyclics LLC, an AbbVie company.

NEW TECHNOLOGY IN MEDICINE IS AWESOME!

New technology in medicine is awesome! 

https://www.youtube.com/watch?v=27eUg20QRVI

NEW MEDICAL ACHIEVEMENT FOR THE CURE OF KIDNEY CANCER: FDA approves Opdivo to treat advanced form of kidney cancer

The U.S. Food and Drug Administration today approved Opdivo (nivolumab) to treat patients with advanced (metastatic) renal cell carcinoma, a form of kidney cancer, who have received a certain type of prior therapy.

“Opdivo provides an important therapy option for patients with renal cell carcinoma,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “It is one of few therapies that have demonstrated the ability to extend patients’ survival in treating this disease.” Torisel (temsirolimus), approved in 2007, is the only other FDA-approved therapy that has demonstrated overall survival in renal cell cancer.

Renal cell carcinoma is the most common form of kidney cancer in adults and forms in the tissues of the kidney that make urine. The National Cancer Institute estimates 61,560 new cases and 14,080 deaths from kidney and renal pelvis cancer in the United States this year. 

“Additionally, Opdivo’s extended indication, from melanoma and non-small cell lung cancer to renal cell cancer, demonstrates how immune therapies can benefit patients across a wide range of tumors,” continued Dr. Pazdur.

Opdivo works by targeting the cellular pathway known as PD-1/PD-L1 (proteins found on the body’s immune cells and some cancer cells). By blocking this pathway, Opdivo may help the body’s immune system fight cancer cells. Opdivo is intended for use in renal cell carcinoma in patients who have received prior anti-angiogenic therapy (treatments that interfere with the blood vessels that contribute to the growth of cancerous cells).

The safety and efficacy of Opdivo for this use were demonstrated in an open-label, randomized study of 821 patients with advanced renal cell carcinoma whose disease worsened during or after treatment with an anti-angiogenic agent. Patients were treated with Opdivo or another type of kidney cancer treatment called everolimus (marketed as Afinitor). Those treated with Opdivo lived an average of 25 months after starting treatment compared to 19.6 months in those treated with Afinitor. This effect was observed regardless of the PD-L1 expression level of patients’ renal cell tumors. Additionally, 21.5 percent of those treated with Opdivo experienced a complete or partial shrinkage of their tumors, which lasted an average of 23 months, compared to 3.9 percent of those taking Afinitor, lasting an average of 13.7 months.

The most common side effects of Opdivo for this use are conditions relating to abnormal weakness or lack of energy (asthenic conditions), cough, nausea, rash, difficulty breathing (dyspnea), diarrhea, constipation, decreased appetite, back pain and joint pain (arthralgia).

Opdivo also has the potential to cause serious side effects that result from the immune system effect of Opdivo (known as “immune-mediated side effects”). These severe immune-mediated side effects involve healthy organs, including the lung, colon, liver, kidneys, hormone-producing glands and the brain.  

The FDA granted the Opdivo application a breakthrough therapy designation, fast track designation, and priority review status. These are distinct programs intended to facilitate and expedite the development and review of certain new drugs in light of their potential to benefit patients with serious or life-threatening conditions.  

Opdivo is marketed by Bristol-Myers Squibb based in Princeton, New Jersey. Torisel is marketed by Pfizer, based in New York, New York. Afinitor is marketed by Novartis Pharmaceuticals of East Hanover, New Jersey.

Source: FDA web page

VALUE-BASED CANCER CARE

Robert C. Young, M.D.

November 18, 2015DOI: 10.1056/NEJMp1508387

     

     In June 2015, the American Society of Clinical Oncology (ASCO) published a proposed framework for assessing the value of various cancer treatments.1 The goal was to evaluate selected treatment regimens on the basis of their clinical benefit, toxicity, and cost. ASCO's ideas about cost had been incubating for a long time: the organization had created a Task Force on the Cost of Cancer Care in 2007, although, like most medical specialty organizations, it had generally remained silent on the issue of cost. But the cost of cancer care has been growing rapidly: though it accounts for a relatively small portion of overall U.S. health care expenditures, it is expected to increase from $125 billion in 2010 to $158 billion in 2020.

     The costs of cancer drugs amount to only 5 to 20% of the total costs of cancer care, depending on how many of the multiple cost components are included. But the average cost of some newer cancer drugs is now $10,000 to $30,000 per month, and combinations of checkpoint inhibitors cost as much as $100,000 per month. Virtually none of these treatments are curative, and some improve only disease-free survival, not overall survival. The costs of copayments, out-of-pocket expenses, and rising insurance premiums exceed many patients' capacity to pay. A 20% copayment for checkpoint inhibitors might cost the patient $60,000 for a full course of treatment. Many patients elect to simply forgo treatment.

More in the following link…

http://www.nejm.org/doi/full/10.1056/NEJMp1508387?query=TOC

Source: NEJM

MAYO RESEARCHERS FIND CANCER BIOPSIES DO NOT PROMOTE CANCER SPREAD

Mayo Researchers Find Cancer Biopsies Do Not Promote Cancer Spread

JACKSONVILLE, Fla. — A study of more than 2,000 patients by researchers at Mayo Clinic’s campus, has dispelled the myth that cancer biopsies cause cancer to spread. In the Jan. 9 online issue of Gut, they show that patients who received a biopsy had a better outcome and longer survival than patients who did not have a biopsy.

The image shows a pancreas tumor being biopsied with a needle as visualized by endoscopic ultrasound. The endoscope was located within the stomach (passed via the mouth). An ultrasound probe at the tip of the endoscope allows visualization of the pancreas which is located immediately next to the stomach. A long needle is guided through the endoscope and into the tumor under ultrasound guidance.

The researchers studied pancreatic cancer, but the findings likely apply to other cancers because diagnostic technique used in this study — fine needle aspiration — is commonly used across tumor types, says the study’s senior investigator and gastroenterologist Michael Wallace, M.D.

Fine needle aspiration is a minimally invasive technique that uses a thin and hollow needle to extract a few cells from a tumor mass. A long-held belief by a number of patients and even some physicians has been that a biopsy can cause some cancer cells to spread.

While there have been a few case reports that suggest this can happen — but very rarely — there is no need for patients to be concerned about biopsies, says Dr. Wallace.

“This study shows that physicians and patients should feel reassured that a biopsy is very safe,” he says. “We do millions of biopsies of cancer a year in the U.S., but one or two case studies have led to this common myth that biopsies spread cancer.”

Biopsies offer “very valuable information that allow us to tailor treatment. In some cases, we can offer chemotherapy and radiation before surgery for a better outcome, and in other cases, we can avoid surgery and other therapy altogether,” Dr. Wallace says.

Surgery for pancreatic cancer is “a very big operation,” and “most people should want to make sure they have cancer before they undergo surgery,” he says. One study has shown that 9 percent of patients who underwent surgery because of suspected pancreatic cancer actually had benign disease.

Dr. Wallace and his team have conducted two separate studies to examine the risk of biopsy.

In a 2013 study published in Endoscopy, the researchers examined outcomes in 256 pancreatic cancer patients treated at Mayo Clinic in Jacksonville, Florida. They found no difference in cancer recurrence between 208 patients who had ultrasound-guided fine needle aspiration (EUS-FNA) and the 48 patients who did not have a biopsy.

In the current study, they examined 11 years (1998–2009) of Medicare data on patients with non-metastatic pancreatic cancer who underwent surgery. The researchers examined overall survival and pancreatic cancer-specific survival in 498 patients who had EUS-FNA and 1,536 patients who did not have a biopsy.

During a mean follow-up time of 21 months, 285 patients (57 percent) in the EUS-FNA group and 1,167 patients (76 percent) in the non-EUS-FNA group died. Pancreatic cancer was identified as the cause of death for 251 patients (50 percent) in the EUS-FNA group and 980 patients (64 percent) in the non-EUS-FNA group.

Median overall survival in the EUS-FNA group was 22 months compared to 15 months in the non-EUS-FNA group.

“Biopsies are incredibly valuable. They allow us to practice individualized medicine — treatment that is tailored for each person and designed to offer the best outcome possible,” Dr. Wallace says.

Source: Mayo Clinic News Network

A SIMPLE TECHNIQUE MAY BE MOST EFFECTIVE IN PREVENTING HEART DISEASE AFTER RADIATION THERAPY FOR BREAST CANCER

 Women who have breast cancer on their left side present a particular challenge to radiation oncologists. Studies have shown that the risk of heart disease is higher in this group of women after radiation treatment because it can be difficult to ensure that a sufficient dose of radiation is delivered to the left breast while adequately shielding the heart from exposure. New research shows a woman who holds her breath during radiation pulses can greatly reduce radiation exposure to the heart.

"Radiation therapy is commonly prescribed to patients with breast cancer following surgery as a component of first-line therapy," said first author Harriet Eldredge-Hindy, M.D., a Chief Resident and researcher in the Department of Radiation Oncology at Thomas Jefferson University "We wanted to determine how effective breath-hold could be in shielding the heart from extraneous radiation exposure during treatment of the left breast."

Recent studies have shown women with cancer in the left breast are at higher risk of heart disease, and that the risk increases proportionately with the dose of radiation the heart is exposed to during treatment. A number of techniques have been developed to reduce exposure to the heart including prone positioning (lying flat on the belly on a bed that only exposes the left breast), intensity-modulated radiation therapy (IMRT), and accelerated partial breast irradiation. The breath-hold technique allows doctors to monitor a patient's breath for the position that shifts the heart out of the range of the radiation beam.

In the largest prospective study to date, following women for 8 years post treatment, 81 women were asked to hold their breath during radiation treatment for breast cancer- a process that was repeated until therapeutic dose was reached. The researchers found that patients capable of holding their breath over the course of treatment had a 90 percent disease-free survival, and a 96 percent overall survival, with a median reduction in radiation dose to the heart of 62 percent. The findings were published online this week in the journal Practical Radiation Oncology.

"Given that this technique helps to shield the heart during radiation treatment for breast cancer," said Rani Anne, M.D., Associate Professor of Radiation Oncology at Thomas Jefferson University and senior author on the study, "we routinely offer breast cancer treatment with the breath hold technique at Jefferson."

Source: EurekAlert