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by Dagny Stuart | Posted on Thursday, Jun. 19, 2014 — 8:26 AM
Early research suggests patients with advanced melanoma — the most deadly form of skin cancer — may benefit from both immunotherapies and targeted therapies aimed at specific gene mutations. However, no combinations of these two classes of drugs have been shown to be safe, so far.
The results of the first such combination study with more promising outcomes were reported by lead author Igor Puzanov, M.D., MSCI, associate professor of Medicine at Vanderbilt-Ingram Cancer Center, during the annual meeting of the American Society of Clinical Oncology (ASCO), held May 30 to June 3 in Chicago.
Puzanov was among nearly 20 VICC investigators who presented research findings during the ASCO conference, which attracts nearly 30,000 cancer researchers and other participants from around the world.
Melanoma patients whose tumors harbor a BRAF V600 gene mutation were enrolled in the Phase 1b study testing the safety of a two drug combination — the BRAF inhibitor dabrafenib plus ipilimumab (Ipi), an immunotherapy drug — or those two treatments plus the MEK inhibitor drug trametinib. A previous study using Ipi with a different BRAF inhibitor, vemurafenib, led to unacceptable liver toxicity.
Puzanov presented early results of the new study, which indicated that the combination of dabrafenib and ipilimumab was tolerable, with no significant effects on liver function.
However, the three-drug combination led to surprising levels of colitis, suggesting a potent synergy among dabrafenib, trametinib and ipilimumab.
In a separate poster highlight session, Puzanov also reported on a Phase 1b/2 study of ipilimumab plus T-VEC, an oncolytic virus engineered to stimulate the immune system. Early signals from this study show the combination may be more effective than Ipi alone, with a 56 percent response rate.
“After decades of research, we finally have new therapies that are producing better results for many melanoma patients, but it is clear that we may have to combine some of these therapies for optimal outcomes. These early studies are showing encouraging results,” Puzanov said.
In other ASCO news, Jeffrey Sosman, M.D., director of the Melanoma and Immunotherapy Program, reported on the investigational drug LEE011, a CDK 4/6 inhibitor used in combination with the MEK inhibitor binimetinib in patients whose tumors show an NRAS mutation. The early activity showed a 33 percent overall response rate, a promising result in this aggressive subtype of melanoma.
While many positive developments in cancer therapy were announced at the conference, reporting on the 2013 Institute of Medicine Report “Delivering High-Quality Cancer Care,” Michael Neuss, M.D., chief medical officer at VICC, said these advances won’t be available to all patients unless organizations and governments address issues of accessibility and affordability of cancer care.
During an ASCO education session, Neuss noted that the “National Healthcare Disparities Report 2013” from the U.S. Department of Health and Human Services found that disparities are increasing for cancer screening, with access to mammography and colonoscopy screening varying according to income level. Without screening for early detection, some groups of cancer patients have worse outcomes.
“The bottom line is that more African-Americans are dying with breast cancer than Caucasians,” said Neuss.
The Patient Protection and Affordable Care Act increases coverage for some preventive services, including mammography and screening for colorectal and cervical cancer, but this expanded coverage will not be available for patients in states like Tennessee that did not expand Medicaid coverage.
“It makes a real difference in health outcomes for patients with no access to health care who are in either racially disadvantaged or income-disadvantaged populations,” Neuss said.
Dagny Stuart, (615) 936-7245
Health and Medicine, Reporter, Research American Society of Clinical Oncology, cancer, featured-Reporter, Igor Puzanov, Jeffrey Sosman, melanoma, Michael Neuss, Reporter June 20 2014, skin cancer, Vanderbilt Ingram Cancer Center
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