Cancer Immunotherapy 'Has Entered Mainstream'

“Cancer immunotherapy takes centre stage in a series of articles about harnessing the immune system for therapy published March 25 as a special issue of Science Translational Medicine.

“While the articles trace the progress being made across all fields of medicine, it is in cancer that immunotherapy has made the greatest strides.

” ‘Recent treatment successes with antibodies that regulate immune activation have essentially ended the debate about whether the immune system sees and regulates cancer growth. Tumor immunotherapy has entered the mainstream and is a strategy to be considered within the clinician’s toolbox of standard therapies for cancer,’ write Alexander M. Lesokhin, MD, from Memorial Sloan Kettering Cancer Center in New York City, and colleagues in a perspective.”

In NSCLC, Why Some Patients Respond to Immunotherapy

“Immunotherapy with drugs that act on the program death (PD) pathway offers a novel approach to the treatment of non–small cell lung cancer (NSCLC), and a new study provides insights into how these drugs may result in lasting and durable responses in these patients.

“The new study, published online on March 12 in Science, suggests that patients with a high mutational burden in their tumors may be most likely to benefit from treatment with a PD-1 inhibitor.

” ‘The study suggests that the genomic landscape of lung cancers shapes the response to anti-PD-1 therapy,’ corresponding author Timothy Chan, MD, PhD, cancer geneticist in the Human Oncology and Pathogenesis Program and vice chair of radiation oncology at the Memorial Sloan Kettering Cancer Center (MSKCC), in New York City, commented in an institution press release.”

NCCN Recommends Only One Genomic Test for Breast Cancer

“The National Comprehensive Cancer Network (NCCN) only endorses one genomic test for use in patients with early-stage breast cancer, according to a presenter here at the NCCN 20th Annual Conference.

“Oncotype DX, a 21-gene assay from Genomic Health, has won that honor, said presenter Amy Cyr, MD, from the Siteman Cancer Center at Washington University in St. Louis, Missouri.

“The test serves two functions. In addition to providing a prognosis, the test has ‘some prediction capabilities in terms of therapy; it actually predicts a response to chemotherapy, compared with no chemotherapy,’ she explained.”

New Test to Aid Melanoma Diagnosis: Ready for Clinical Use?

“Differentiating between malignant melanoma and benign skin moles can be difficult in about 15% of cases, where histopathologic analysis is not straightforward because of ambiguous findings.

“A new 23-gene signature test (myPath Melanoma, Myriad Genetics) could be helpful in these instances, researchers working with the company suggest.

“The test was developed with a training set and then validated in an independent cohort. The results were published online March 2 in the Journal of Cutaneous Pathology.

” ‘myPath Melanoma is a powerful new molecular diagnostic test that analyzes genetic information inside skin cells to help us understand the biology of a patient’s skin lesion and objectively differentiate benign moles from potentially lethal melanomas,’ researcher Loren Clarke, MD, medical director for dermatology at Myriad, said in a company press release.”

Hospice Care Lowers Cost and ICU Use in Cancer Patients

“Hospice care at the end of life can significantly lower rates of hospitalization, intensive care unit (ICU) admission, and invasive procedures for cancer patients, according to a new study. Not surprisingly, it can also significantly lower healthcare costs.

“The study, which was published in the November 12 issue ofJAMA, adds further evidence to research that has shown that hospice care can reduce aggressive medical interventions and healthcare costs.

“The researchers, led by Ziad Obermeyer, MD, MPhil, from Brigham and Women’s Hospital and Harvard Medical School in Boston, looked at poor-prognosis cancers (lung, brain, pancreatic, any metastatic or ill-defined malignancy, and hematologic malignancies designated as relapsed or not in remission). They compared the use and costs of healthcare in Medicare patients who received hospice care and in those who did not.

“From a national sample of Medicare fee-for-service beneficiaries who died in 2011, the team identified 86,851 patients with poor-prognosis cancers, 60% of whom entered hospice before death.

Skipping ALND in Some Early Breast Cancers Is Criticized

“The American Society of Clinical Oncology’s (ASCO’s) new recommendation that that some women with early-stage breast cancer and minimal lymph node involvement can forgo extensive lymph node surgery has been questioned separately by two sets of clinicians.

“The guidelines were originally published in May 1 in the Journal of Clinical Oncology (JCO), the flagship journal of ASCO.

“Now, in letters to the journal published on September 22, critics are saying that there is not enough evidence to support the recommendation.

“But the investigators of the trial on which the recommendation is based argue back, saying it is time to skip the surgery in certain patients.”

New Standard in Melanoma: Combo of BRAF and MEK Inhibitors

The gist: Two new, similar melanoma treatments have been tested in clinical trials—research studies with volunteer patients. Both of the trials are focused on people with advanced melanoma whose tumors have mutations in the BRAF gene. Such patients are often treated with a targeted therapy called a BRAF inhibitor, but their tumors often become resistant and keep growing. In these two trials, the researchers hope that combining BRAF inhibitors with other targeted drugs known as MEK inhibitors might help patients avoid resistance. One of the trials tested a combination of the drugs vemurafenib and cobimetinib. The other trial combined dabrafenib and trametinib. In both trials, patients treated with the combination treatment fared better than patients treated with just a BRAF inhibitor alone.

“For patients with advanced melanoma that isBRAF-mutation positive, the combination of a BRAF and MEK inhibitor works better than a BRAF inhibitor alone. The data come from 2 phase 3 trials presented here at the presidential session of the European Society for Medical Oncology (ESMO) Congress 2014.

“Experts here say that such combinations should be the new standard of care in this patient population, which accounts for about 40% of all melanoma.

“At present, the first-line treatment for these patients is a BRAF inhibitor used alone, but while these drugs can elicit dramatic responses, they do not last, and after about 5 or 6 months, patients relapse. The tumor develops resistance to the drug via the MAPK pathway, and this is blocked by a MEK inhibitor. Adding a MEK inhibitor to the BRAF inhibitor from the beginning of treatment blocks this resistance pathway and improves outcomes.

“The 2 new trials are known as COMBI-v and coBRIM.

“Both studies used vemurafenib (Zelboraf, Roche/Plexxikon) as the single BRAF inhibitor, but each used a different combination of BRAF and MEK inhibitor.”

Rinse Eases Symptoms of Oral Mucositis in Cancer Patients

“A rinse for oral mucositis has been shown to offer significantly better symptom improvement than placebo in a randomized controlled trial. The mucoadhesive hydrogel (MuGard, Access Pharmaceuticals) coats the oral cavity and mucous membranes, and was approved by the US Food and Drug Administration (FDA) in 2006.

“The manufacturer-sponsored study, published in the May 1 issue of Cancer, is the first randomized placebo-controlled trial of a medical product for oral mucositis, the researchers report.

“Oral mucositis can be a debilitating adverse effect of cancer treatment, and can affect more than 40% of patients receiving radiation or chemotherapy, write Ron Allison, MD, radiation oncologist and medical director at 21st Century Oncology Carolina Radiation Medicine in Greenville, North Carolina, and colleagues. It can interfere with the intake of nutrition and fluids, and can lead to hospitalization and the placement of a feeding tube. Oral mucositis can also interrupt cancer treatment, reducing disease control and survival. In some cases, it can be life-threatening.”

Drugs to Avoid in Patients on Tyrosine Kinase Inhibitors

Editor’s note: More and more people with cancer are being treated with drugs known as tyrosine kinase inhibitors (TKIs). As with any other drug, oncologists who prescribe TKIs must be aware of other drugs a patient is taking to ensure there will not be a dangerous drug-drug interaction. Researchers recently published a report outlining known and potential drug-drug interactions between TKIs and other drugs. Oncologists and patients may wish to take these into account when considering cancer treatment with TKIs.

“With the rapid and widespread uptake of tyrosine kinase inhibitors (TKIs) in oncology over the past several years, serious drug–drug interactions are an “increasing risk,” according a new report.

“To guarantee the safe use of TKIs, ‘a drugs review for each patient is needed,’ write Frank G.A. Jansman, PharmD, PhD, from Deventer Hospital in the Netherlands, and colleagues in a review published in the July issue of the Lancet Oncology.

“The review provides a comprehensive overview of known and suspected interactions between TKIs and conventional prescribed drugs, over-the-counter drugs, and herbal medicines.

“All 15 TKIs approved to date by the US Food and Drug Administration or the European Medicines Agency are evaluated.

“They are axitinib (Inlyta, Pfizer), crizotinib (Xalkori, Pfizer), dasatinib (Sprycel, Bristol-Myers Squibb and Otsuka America), erlotinib (Tarceva, Osi Pharmaceuticals), gefitinib (Iressa, AstraZeneca), imatinib (Gleevec, Novartis), lapatinib (Tykerb, GlaxoSmithKline), nilotinib (Tasigna, Novartis), pazopanib (Votrient, GlaxoSmithKline), regorafenib (Stivarga, Bayer), ruxolitinib (Jakafi, Incyte), sorafenib (Nexavar, Bayer), sunitinib (Sutent, Pfizer), vandetanib (Caprelsa, AstraZeneca), and vemurafenib (Zelboraf, Roche).”