Claim: In Early Trial, Targeted Therapy Fights Advanced Melanoma
Verdict: SUPPORTS

Retrieved passages:
title: Melanoma
text: therapies work by blocking the genes involved in pathways for tumor proliferation and survival. The main treatments are BRAF, C-Kit and NRAS inhibitors. These inhibitors work to inhibit the downstream pathways involved in cell proliferation and tumour development due to specific gene mutations. People can be treated with small-molecule targeted inhibitors if they are positive for the specific mutation. BRAF inhibitors, such as vemurafenib and dabrafenib and a MEK inhibitor trametinib are the most effective, approved treatments for BRAF positive melanoma. Melanoma tumors can develop resistance during therapy which can make therapy no longer effective, but combining the use of

title: Melanoma
text: Clinical Oncology Conference in June 2010, the Bristol-Myers Squibb pharmaceutical company reported the clinical findings of their drug ipilimumab. The study found an increase in median survival from 6.4 to 10 months in patients with advanced melanomas treated with the monoclonal ipilimumab, versus an experimental vaccine. It also found a one-year survival rate of 25% in the control group using the vaccine, 44% in the vaccine and ipilimumab group, and 46% in the group treated with ipilimumab alone. However, some have raised concerns about this study for its use of the unconventional control arm, rather than comparing the drug against

title: Melanoma
text: Plexxicon's vemurafenib could lead to substantial tumor regression in a majority of patients if their tumor contain the B-Raf mutation. In June 2011, a large clinical trial confirmed the positive findings from those earlier trials. In August 2011 Vemurafenib received FDA approval for the treatment of late-stage melanoma. In May 2013 the US FDA approved dabrafenib as a single agent treatment for patients with BRAF V600E mutation-positive advanced melanoma. Some researchers believe that combination therapies that simultaneously block multiple pathways may improve efficacy by making it more difficult for the tumor cells to mutate before being destroyed. In October 2012

title: BRAF (gene)
text: well-understood, high yield target. Vemurafenib (RG7204 or PLX4032) was licensed by the US Food and Drug Administration as Zelboraf for the treatment of metastatic melanoma in August 2011 based on Phase III clinical data. Improved survival was seen, as well as a response rate to treatment of 53%, compared to from 7-12% with the former best chemotherapeutic treatment, dacarbazine. In clinical trials, B-Raf increased metastatic melanoma patient chance of survival. In spite of the drug's high efficacy, 20% of tumors still develop resistance to the treatment. In mice, 20% of tumors become resistant after 56 days. While the mechanisms of

title: Melanoma
text: a placebo or standard treatment. The criticism was that although Ipilimumab performed better than the vaccine, the vaccine has not been tested before and may be causing toxicity, making the drug appear better by comparison. Ipilimumab was approved by the FDA in March 2011 to treat patients with late-stage melanoma that has spread or cannot be removed by surgery. In June 2011, a clinical trial of ipilimumab plus dacarbazine combined this immune system booster with the standard chemotherapy drug that targets cell division. It showed an increase in median survival for these late stage patients to 11 months instead of

title: Pembrolizumab
text: USAN name was changed from lambrolizumab to pembrolizumab. In that year clinical trial results in advanced melanoma were published in the New England Journal of Medicine. This was part of the large phase 1 NCT01295827 trial. On September 4, 2014, the US Food and Drug Administration (FDA) approved pembrolizumab under the FDA Fast Track Development Program. It is approved for use following treatment with ipilimumab, or after treatment with Ipilimumab and a BRAF inhibitor in advanced melanoma patients who carry a BRAF mutation. As of 2015, the only PD-1/PD-L1 targeting drugs on the market were pembrolizumab and Bristol-Myers Squibb's Opdivo,

title: H. Lee Moffitt Cancer Center & Research Institute
text: Adam Comprehensive Melanoma Research Center at Moffitt, and researchers at Moffitt Cancer Center discovered two monotherapy drugs – Mekinist (trametinib) and Tafinlar (dabrafenib) – can be safely combined to overcome or delay treatment resistance for a large percentage of melanoma patients with a specific gene mutation. Approved by the FDA in January 2014, Mekinist in combination with Tafinlar is one of the biggest advancements in melanoma treatment in the past 30 years. In August 2011, the U.S. Food and Drug Administration (FDA) approved the drug vemurafenib (Zelboraf) for metastatic melanoma patients who test positive for a specific gene mutation. Moffitt

title: Melanoma
text: categories of treatments including cytokines, immune check point inhibitors, and adoptive cell transfer. These treatment options are most often used in people with metastatic melanoma and significantly improves overall survival. However, these treatments are often costly. For example, one immune check point inhibitor treatment, pembrolizumab, costs $10,000 to $12,000 USD for a single dose administered every 3 weeks. Cytokine therapies used for melanoma include IFN-a and IL-2. IL-2 (Proleukin) was the first new therapy approved (1990 Europe, 1992 USA) for the treatment of metastatic melanoma in 20 years. IL-2 may offer the possibility of a complete and long-lasting remission in

title: Adjuvant therapy
text: 2 weeks. To lessen the side effects of chemotherapy that can be exacerbated with more closely administered chemotherapy treatments, growth factors are typically given in conjunction with DDC to restore white blood cell counts. A recent 2018 meta-analysis of DDC clinical trials in early stage breast cancer patients indicated promising results in premenopausal women, but DDC has yet to become the standard of treatment in clinics. The role of adjuvant therapy in malignant melanoma is and has been hotly debated by oncologists. In 1995 a multicenter study reported improved long-term and disease-free survival in melanoma patients using interferon alpha 2b

title: Melanoma
text: BRAF and MEK inhibitors may create a fast and lasting melanoma therapy response. A number of treatments improve survival over traditional chemotherapy. Biochemotherapy (chemotherapy with cytokines IL-2 and IFN-α) combined with BRAF inhibitors improved survival for people with BRAF positive melanoma. Biochemotherapy alone did not improve overall survival and had higher toxicity than chemotherapy. Combining multiple chemotherapy agents (polychemotherapy) did not improve survival over monochemotherapy. Immunotherapy is aimed at stimulating the person’s immune system against the tumor, by enhancing the body's own ability to recognize and kill cancer cells. The current approach to treating melanoma with immunotherapy includes three broad

title: Ipilimumab
text: In 2013 a trial was running that compared ipilimumab alone against ipilimumab in combination with nivolumab. The response rate (tumours shrinking by at least 30%) was 58% for the combination, 44% for nivolumab alone, and 19% for ipilimumab alone. This combination gained FDA approval for melanoma in Oct 2015. In March 2014, an open-label, randomized, two agent, single center trial started combining ipilimumab with phosphatidylserine-targeting immunotherapy bavituximab for the treatment of advanced melanoma. The number of treated patients in arm A (ipilimumab plus bavituximab) was to be 16, with 8 in arm B (ipilimumab only). The trial was expected to

title: Head and neck cancer
text: tumors. Amphinex is giving good results in early clinical trials for treatment of advanced head and neck cancer. Targeted therapy, according to the National Cancer Institute, is "a type of treatment that uses drugs or other substances, such as monoclonal antibodies, to identify and attack specific cancer cells without harming normal cells." Some targeted therapy used in squamous cell cancers of the head and neck include cetuximab, bevacizumab and erlotinib. The best quality data are available for cetuximab since the 2006 publication of a randomized clinical trial comparing radiation treatment plus cetuximab versus radiation treatment alone. This study found that

title: Pembrolizumab
text: development program was directed to around 30 cancers and that it was running over 270 clinical trials (around 100 in combination with other treatments) and had four registration-enabling studies in process. Results of a Phase II clinical trial in Merkel-cell carcinoma were reported in the New England Journal of Medicine in June 2016. Results of a clinical trial in people with untreatable metastases arising from various solid tumors were published in "Science" in 2017. It is in a phase III trial in combination with epacadostat, an Indoleamine 2,3-dioxygenase (IDO1) inhibitor to treat melanoma. Pembrolizumab Pembrolizumab (formerly MK-3475 and lambrolizumab, trade

title: Pembrolizumab
text: chances of proving the drug would work and would make clinical trials faster. (The trials would need fewer patients because of the likelihood of greater effect size.) Moving quickly and reducing the risk of failure was essential for catching up with Bristol-Myers Squibb, which had an approximate five year lead over Merck. The phase I study started in early 2011, and Eric Rubin, who was running the melanoma trial, argued for and was able to win expansion of the trial until it reached around 1300 people. This was the largest Phase I study ever run in oncology, with the patients

title: Vemurafenib
text: has efficacy against the rarer BRAF V600K mutation. Melanoma cells without these mutations are not inhibited by vemurafenib; the drug paradoxically stimulates normal BRAF and may promote tumor growth in such cases. Three mechanisms of resistance to vemurafenib (covering 40% of cases) have been discovered: In a phase I clinical study, vemurafenib (then known as PLX4032) was able to reduce numbers of cancer cells in over half of a group of 16 patients with advanced melanoma. The treated group had a median increased survival time of 6 months over the control group. A second phase I study, in patients with

title: Melanoma
text: in medicine do not use the word for benign tumors. Pharmacotherapy research for unresectable or metastatic malignant melanoma is ongoing. In clinical research setting other therapies, such as adoptive cell therapy or gene therapy, are being tested. Two kinds of experimental treatments developed at the National Cancer Institute (NCI), have been used in metastatic melanoma with tentative success. The first treatment involves adoptive cell therapy (ACT) using TILs immune cells (tumor infiltrating lymphocytes) isolated from a person's own melanoma tumor. These cells are grown in large numbers in a laboratory and returned to the patient after a treatment that temporarily

title: Neutron capture therapy of cancer
text: disease of the genital region with impressive clinical results. The first clinical trial of BNCT in Argentina for the treatment of melanomas was performed in October 2003 and since then several patients with cutaneous melanomas have been treated as part of a Phase II clinical trial at the RA-6 nuclear reactor in Bariloche. The neutron beam has a mixed thermal-hyperthermal neutron spectrum that can be use to treat superficial tumors. Finally, as recently reported, the in-hospital neutron irradiator (IHNI) in Beijing has been used to treat three patients with cutaneous melanomas with a complete response of the primary lesion and

title: Programmed cell death protein 1
text: a response. Nivolumab (Opdivo, Bristol-Myers Squibb) was approved in Japan in July 2014 and by the US FDA in December 2014 to treat metastatic melanoma. Pembrolizumab (Keytruda, MK-3475, Merck), which also targets PD-1 receptors, was approved by the FDA in Sept 2014 to treat metastatic melanoma. Pembrolizumab has been made accessible to advanced melanoma patients in the UK via UK Early Access to Medicines Scheme (EAMS) in March 2015. It is being used in clinical trials in the US for lung cancer, lymphoma, and mesothelioma. It has had measured success, with little side effects. It is up to the manufacturer

title: Targeted alpha-particle therapy
text: was the first α-emitter approved by the FDA in the United States for treatment of bone metastases from prostate cancer, and is a recommended treatment in the UK by NICE. In a phase III trial comparing Ra to a placebo, survival was significantly improved. Early trials of Ac and Bi have shown evidence of anti-tumour activity in Leukaemia patients. Phase I trials on melanomas have shown Bi is effective in causing tumour regression. The short path length of alpha particles in tissue, which makes them well suited to treatment of the above types of disease, is a negative when it

title: Ipilimumab
text: melanoma that has spread or cannot be removed by surgery. It was later approved by the US FDA on October 28, 2015 for stage 3 patients as adjuvant therapy. On February 1, 2012, Health Canada approved ipilimumab for "treatment of unresectable or metastatic melanoma in patients who have failed or do not tolerate other systemic therapy for advanced disease." Ipilimumab was approved in the European Union (EU), for second line treatment of metastatic melanoma in November 2012. On April 16, 2018, the FDA approved for advanced renal cell carcinoma the combination therapy Opdivo and Yervoy, both owned by Bristol-Myers Squibb.