“Cost regulators for the National Health Service in England and Wales have this morning issued guidance recommending the use of Bristol-Myers Squibb’s Yervoy (ipilimumab) for skin cancer and Astellas’ Xtandi (enzalutamide) for prostate cancer.
“First-line use of Yervoy will be funded in patients with advanced malignant melanoma when the full tumour cannot be removed or the cancer has spread to other parts of the body.
“The drug costs £3,750 per 10-ml vial or £15,000 per 40-ml vial, but B-MS has also agreed a patient access scheme with the Department of Health, in which it will be sold to the NHS at a discounted price.
“NICE analysis concluded that the most plausible cost per Quality Adjusted Life Year (QALY) was £47,900 for Yervoy compared with the chemotherapy dacarbazine and £28,600 per QALY compared with Roche’s Zelboraf (vemuraf [sic]).”
The gist: Researchers have conducted a clinical trial with volunteer patients to test a new melanoma treatment that combines the drugs cobimetinib and vemurafenib. The participants all had melanoma tumors with BRAFV600 mutations. People with BRAFV600 mutations often become resistant to treatment if they take a “BRAF inhibitor” like vemurafenib. The hope is that drugs like cobimetinib can be given alongside vemurafenib to circumvent resistance. The researchers found that the combination treatment was safe for these patients, and there was some promising evidence that the treatment was effective, but more follow-up will be needed.
“Combined treatment of BRAFV600-mutated melanoma with the MEK inhibitor cobimetinib and the BRAF inhibitor vemurafenib was safe and tolerable, according to the results of a phase Ib study.
“Based on the promising antitumor activity seen with the combination, researchers led by Antoni Ribas, MD, of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, and colleagues recommended further clinical development and testing of this combination.
“According to background information published with the study in Lancet Oncology, patients with BRAFV600-mutated metastatic melanoma often develop resistance to treatment with a BRAF inhibitor, ‘which frequently reactivates the MAPK pathway through MEK.’ Prior research has shown that sequential treatment with a MEK inhibitor after this progression does not result in meaningful antitumor activity.”
The gist: In the U.S. and Australia, oncologists are allowed to prescribe a treatment that combines the drugs Mekinist (trametinib) and Tafinlar (dabrafenib) for people with unresectable or metastatic melanoma whose tumors have a V600E or V600K mutation in the BRAF gene. European regulators would like to see more data on the benefits and risks of the treatment before approving it for European patients. The company that produces the treatment was conducting a clinical trial with volunteer patients to capture that data, but has now decided to halt the trial, which was comparing the combo treatment to the drug Zelboraf (vemurafenib). The trial found that the combo treatment has such a significant improvement on patient survival that the patients who had been taking vemurafenib for comparison should be allowed to switch to the combo treatment, and the trial ended early.
“GlaxoSmithKline has stopped a Phase III study of its combination therapy for advanced cutaneous melanoma ahead of schedule after it showed a significant survival benefit.
“The UK drug giant said an Independent Data Monitoring Committee (IDMC) has made the recommendation as it emerged patients with metastatic melanoma – carrying a BRAFV600 mutation – who took a combo of Mekinist (trametinib) and Tafinlar (dabrafenib) demonstrated an overall survival benefit compared to those taking vemarufenib.
“Safety signals were also good, remaining consistent with that for the MEK inhibitor and BRAF inhibitor observed to date, the firm said.”
“An experimental drug from Roche helped people with an advanced form of skin cancer live longer without their disease worsening when used in combination with another treatment, the Swiss drugmaker said on Monday.
“Pharmaceutical companies are looking to combination therapy to yield better results and drug cocktails are expected to be crucial as oncologists seek to block cancer on multiple fronts.
“Cobimetinib, which is being developed in collaboration with Exelixis Inc, is designed to be used with another Roche drug called Zelboraf for patients with tumors that have a mutation in a gene known as BRAF that allows melanoma cells to grow.”
Editor’s note: Cobimetinib is meant to be used in combination with the targeted therapy Zelboraf (vemurafenib) to treat people with melanoma whose tumors have a mutation in the BRAF gene. Oncologists can use a method called molecular testing to figure out whether a patient has a BRAF mutation.
Editor’s note: Targeted therapies that fight tumors with specific genetic mutations opened up a new era in cancer treatment, but many patients become resistant to these treatments, and their cancer grows back. A new type of treatment called immunotherapy boosts a patient’s own immune system to fight cancer. Researchers are hopeful that combining targeted drugs with immunotherapy drugs could be highly effective. This article discusses the idea of combining immunotherapy with targeted drugs developed to treat melanomas with mutations in the GRAF gene. It is a scientific article, but may interest some patients and caregivers dealing with BRAF-mutant melanoma.
“Hu–Lieskovan S, et al. – In this review,the authors present the concept and potential mechanisms of combinatorial activity of targeted therapy and immunotherapy, review the literature for evidence to support the combination, and discuss the potential challenges and future directions for rational conduct of clinical trials.
“Recent breakthroughs in the treatment of advanced melanoma are based on scientific advances in understanding oncogenic signaling and the immunobiology of this cancer.
“Targeted therapy can successfully block oncogenic signaling in BRAFV600-mutant melanoma with high initial clinical responses, but relapse rates are also high.
“Activation of an immune response by releasing inhibitory check points can induce durable responses in a subset of patients with melanoma.
“These advances have driven interest in combining both modes of therapy with the goal of achieving high response rates with prolonged duration.
“Combining BRAF inhibitors and immunotherapy can specifically target the BRAFV600 driver mutation in the tumor cells and potentially sensitize the immune system to target tumors.
“However, it is becoming evident that the effects of paradoxical mitogen-activated protein kinase pathway activation by BRAF inhibitors in non–BRAF-mutant cells needs to be taken into account, which may be implicated in the problems encountered in the first clinical trial testing a combination of the BRAF inhibitor vemurafenib with ipilimumab (anti-CTLA4), with significant liver toxicities.”
Every year, new cancer treatment insights are shared at the American Society of Clinical Oncology (ASCO) Annual Meeting. Here are some of the most notable recent developments in melanoma treatment, gleaned from researchers’ presentations at ASCO last month: Continue reading…
“Rapid resistance to vemurafenib – a treatment for a type of advanced melanoma, the deadliest form of skin cancer – could be prevented by blocking a druggable family of proteins, according to research published in Nature Communications today.
“Scientists at the Cancer Research UK Manchester Institute, based at the University of Manchester, have revealed the MLK family of four enzymes ‘undoes’ the tumour-shrinking effects of vemurafenib.”
Editor’s note: This story describes a potential new way to treat melanoma that has become resistant to vemurafenib. While promising, the research is still in preliminary stages, so new treatments are not yet available for patients.
“Accounting for approximately half of all cancers in the United States, skin cancer is widely recognized as the most common cause of cancer nationwide. More than 3.5 million cases of skin cancer are diagnosed each year, and according to the Skin Cancer Foundation, incidences of skin cancer outnumber all combined cases of breast, colon, lung and prostate cancers.
“With the month of May designated as National Skin Cancer Awareness Month, HemOnc Today highlights 10 issues for oncologists and dermatologists to consider for their patients, as well as the new guideline revisions and research regarding the identification, treatment and management of patients with melanoma and skin cancer.”
Immunotherapy may be patients’ biggest hope for transforming cancer treatment. This approach boosts a patient’s own immune system to fight cancer. More and more immunotherapy treatments are showing promise for more and more patients, and Science magazine named immunotherapies 2013’s Breakthrough of the Year. Continue reading…