Novartis’ Tafinlar® (dabrafenib) + Mekinist® (trametinib): first BRAF-targeted therapy for adjuvant treatment of most aggressive form of skin cancer now available on NHS
Sep 17, 2018
More than six people die every day in the UK from melanoma skin cancer1
Dabrafenib + trametinib is first BRAF-targeted therapy made available for people in England and Wales with stage III BRAF-positive melanoma, following surgery2
Dabrafenib + trametinib significantly reduced risk of disease recurrence or death by over 50% compared to placebo after three years2
Dabrafenib + trametinib is the only approved adjuvant treatment for melanoma that can be taken orally at home3
Camberley, UK, September 17th, 2018 – Novartis today announced the first BRAF-targeted treatment for post-surgery stage III melanoma patients, the most aggressive type of skin-cancer, is to be made available for NHS patients in England and Wales following appraisal by NICE (National Institute for Health and Care Excellence). Tafinlar® (dabrafenib) in combination with Mekinist® (trametinib) has been recommended as a cost-effective treatment option for the adjuvant treatment of adult patients with stage III melanoma with a BRAF V600 mutation, following surgery.
Based on the clinical trial results, which showed the drug combination reduced risk of melanoma returning or death by over 50%, the NICE approval comes just days after the European Medicines Agency (EMA) granted approval of the drug’s use in the EU.2
The rapid decision is testament to the cost-effectiveness of the treatment. Over 500 people in the UK are diagnosed with BRAF-mutated stage III melanoma each year. Stage III melanoma means that cancer cells have spread into skin, lymph vessels or lymph glands close to the melanoma but they haven’t spread to more distant parts of the body.11
Until now, there were no reimbursed drug treatments that offered clear benefits for these patients following surgery.5 As a result, nearly half (44%) of those with BRAF V600 mutated melanoma suffer a recurrence within a year after surgery, with the risk that the cancer progresses to an incurable state.2
Dabrafenib + trametinib will be routinely available on the NHS with immediate effect. The combination treatment is a convenient oral therapy that can be taken at home, consisting of five tablets a day (two dabrafenib twice daily and one trametinib once daily).3
“This is really significant for these patients and the melanoma community in England and Wales, as the treatment has the potential to transform the standard of care for people with BRAF-positive stage III melanoma,” said Professor Ruth Plummer, Clinical Professor of Experimental Cancer Medicine, University of Newcastle Upon Tyne. Previously, there were limited treatment options available to patients who had undergone surgery, and the majority would simply have to hope their melanoma would not return.
“We know this can be a stressful and unsettling as over half of all patients with stage III disease will experience a recurrence in the future, leaving people anxious and worried that their disease might return. It is clear that treating patients with dabrafenib and trametinib after their surgery reduces the chance of recurrence”
Melanoma accounts for more deaths than all other skin cancers combined.1,12 There are around 2,400 deaths from melanoma skin cancer in the UK every year, with more than six people dying every day.1
Prior to now, post-surgery radiotherapy was the only NICE reimbursed treatment option and it was only used in specific cases.5,6 As a result, for the majority of post-surgery patients in the UK, a ‘watch and wait’ approach, to see if the cancer progresses to the next stage (comprising regular consultations and routine surveillance), was the accepted standard of care.2,6
Gill Nuttall, CEO of Melanoma UK, said: “Worryingly, we are continuing to see an increase in the number of people in the UK with melanoma, especially among younger people. “The availability of this treatment is a huge step forward for the hundreds of BRAF-positive patients who are currently left with very few options following surgery. The current ‘watch and wait’ approach is an extremely worrying and stressful time for patients and their families.”
Dabrafenib + trametinib combination is the first targeted treatment approved in a class of drug known as tyrosine kinase inhibitors (TKIs) to be given following surgery to reduce the risk of melanoma returning.7 This class of drug blocks molecules within the cells specific to the cancer to slow or stop tumour growth, and have been demonstrated to improve the outcomes of cancer patients.8
The NICE recommendation is based on the findings from the pivotal phase III trial, COMBI-AD, which was the first study to demonstrate a clinical benefit in post-surgery patients receiving a targeted therapy combination for a BRAF V600 mutation.2 The study showed dabrafenib + trametinib significantly reduced the risk of disease recurrence or death by 53% compared to placebo after three years.2 Well over half of patients (58%) treated with the drug combination had no evidence of recurrence three years after their surgery compared to 39% of those who received placebo.2
“The approval of dabrafenib in combination with trametinib will offer marked benefits to many people living with stage III BRAF-positive melanoma in the UK, following surgery. We have worked closely with NICE and NHS England to ensure eligible patients in England and Wales have access to this important treatment option at the earliest opportunity,” said Mari Scheiffele, Novartis Oncology General Manager, UK & Ireland.
The NICE recommendation has been published in its final draft guidance. Novartis is awaiting the NICE Technology Appraisal Guidance, the final step within the NICE approval process, which is scheduled for publication later this year and will be available via the NICE website. The drugs will be immediately available through the Cancer Drugs Fund (CDF) whilst Novartis await the NICE Technology Appraisal.
Notes to Editors The combination of dabrafenib + trametinib has also shown significant results in the metastatic setting and is currently available and funded across the UK for use in patients with unresectable or metastatic melanoma.9 Adverse events (AEs) were consistent with other Tafinlar + Mekinist studies, and no new safety signals were reported.2
About Melanoma There are around 15,400 new cases of melanoma (stages 0-IV) diagnosed in the UK each year approximately half of which have BRAF mutations.1,4 Biomarker tests can determine whether a tumour has a BRAF mutation.4
Melanoma is staged according to the size of the tumour, if it has spread and where it has spread to. In stage III melanoma, tumours have spread to the nearby lymph nodes, presenting a higher risk of recurrence or spread to other parts of the body in the future.5,10 Patients who receive surgical treatment for stage III melanoma may have a high risk of recurrence because sometimes melanoma cells can remain in the body after surgery; almost half (44%) of patients receiving an inactive tablet in the COMBI-AD study had a recurrence of disease within the first year.2 Adjuvant therapy is additional treatment given after surgical resection, and may be recommended for patients with high-risk melanoma to help reduce the risk of melanoma returning.5,9
About COMBI-AD2 The COMBI-AD study evaluated Tafinlar + Mekinist among patients with stage III, BRAF V600E/K-mutant melanoma without prior anticancer therapy, randomized within 12 weeks of complete surgical resection. Patients received the Tafinlar (150 mg BID) and Mekinist (2 mg QD) combination (n = 438) or matching placebos (n = 432). In the initial primary analysis, and after a median follow-up of 2.8 years, the primary endpoint was met in that the combination therapy significantly reduced the risk of disease recurrence or death by 53% vs. placebo (HR: 0.47 [95% CI: 0.39-0.58]; median not yet reached vs. 16.6 months, respectively; p<0.001). Based on updated data with an additional 10 months of follow-up compared to the primary analysis (minimum follow-up of 40 months), the RFS benefit was maintained with an estimated reduction in the risk of disease recurrence or death by 51% vs placebo (HR: 0.49 [95% CI: (0.40-0.59)]. The relapse-free survival benefit among the combination arm was observed across all patient subgroups, including stage III A, B and C. The estimated one-year, two-year, and three-year RFS were consistently higher than placebo (one year: 88% vs. 56%; two year: 67% vs. 44%; three year: 58% vs. 39%).
The combination treatment group also saw an improvement in a key secondary endpoint of OS (HR: 0.57 [95% CI: 0.42-0.79] p=0.0006, which did not cross the predefined interim analysis boundary of p=0.000019 to claim statistical significance). Other secondary endpoints where the combination demonstrated a clinically meaningful benefit include distant metastasis-free survival (DMFS) (HR: 0.51 [95% CI: 0.40-0.65]), and freedom from relapse (FFR) (HR: 0.47 [95% CI: 0.39-0.57]).
About Tafinlar + Mekinist Combination Combination use of Tafinlar + Mekinist in patients with unresectable or metastatic melanoma who have a BRAF V600 mutation is approved in the US, EU, Japan, Australia, Canada and other countries.
Tafinlar + Mekinist Combination Important Safety Information Tafinlar and Mekinist, in combination, may cause serious side effects such as the risk of new cancers, including both skin cancer and nonskin cancer. Patients should be advised to contact their health care professional immediately for a new wart, skin sore, or bump that bleeds or does not heal, or a change in the size or colour of a mole.
When Tafinlar is used in combination with Mekinist, it can cause serious bleeding problems, especially in the brain or stomach, which can lead to death. Patients should be advised to call their health care professional and get medical help right away if they have any signs of bleeding, including headaches, dizziness, or feel weak, cough up blood or blood clots, vomit blood or their vomit looks like “coffee grounds,” or red or black stools that look like tar.
Mekinist, alone or in combination with Tafinlar, can cause inflammation of the intestines or tears in the stomach or intestines that can lead to death. Patients should report to their health care professional immediately if they have any of the following symptoms: bleeding, diarrhoea (loose stools) or more bowel movements than usual, stomach-area (abdomen) pain or tenderness, fever, or nausea.
Tafinlar, in combination with Mekinist, can cause blood clots in the arms or legs, which can travel to the lungs and can lead to death. Patients should be advised to get medical help right away if they have the following symptoms: chest pain, sudden shortness of breath or trouble breathing, pain in their legs with or without swelling, swelling in their arms or legs, or a cool or pale arm or leg.
The combination of Tafinlar and Mekinist can cause heart problems, including heart failure. A patient’s heart function should be checked before and during treatment. Patients should be advised to call their health care professional right away if they have any of the following signs and symptoms of a heart problem: feeling like their heart is pounding or racing, shortness of breath, swelling of their ankles and feet, or feeling lightheaded.
Tafinlar, in combination with Mekinist, can cause severe eye problems that can lead to blindness. Patients should be advised to call their health care professional right away if they get: blurred vision, loss of vision, or other vision changes, seeing colour dots, halo (seeing blurred outline around objects), eye pain, swelling, or redness.
Tafinlar, in combination with Mekinist, can cause lung or breathing problems. Patients should be advised to tell their health care professional if they have new or worsening symptoms of lung or breathing problems, including shortness of breath or cough.
Fever is common during treatment with Tafinlar in combination with Mekinist, but may also be serious. In some cases, chills or shaking chills, too much fluid loss (dehydration), low blood pressure, dizziness, or kidney problems may happen with the fever. Patients should be advised to call their health care professional immediately if they get a fever.
Rash and other skin reactions are common side effects of Tafinlar in combination with Mekinist. In some cases these rashes and other skin reactions can be severe or serious, and may need to be treated in a hospital. Patients should be advised to call their health care professional if they get any of the following symptoms: skin rash that bothers them or does not go away, acne, redness, swelling, peeling, or tenderness of hands or feet, or skin redness.
Some people may develop high blood sugar or worsening diabetes during treatment with Tafinlar in combination with Mekinist. For patients who are diabetic, their health care professional should check their blood sugar levels closely during treatment. Their diabetes medicine may need to be changed. Patients should be advised to tell their health care professional if they have increased thirst, urinate more often than normal, or produce an increased amount of urine.
Tafinlar, in combination with Mekinist, may cause healthy red blood cells to break down too early in people with glucose-6-phosphate dehydrogenase deficiency. This may lead to a type of anaemia called hemolytic anaemia, where the body does not have enough healthy red blood cells. Patients should be advised to tell their health care professional if they have yellow skin (jaundice), weakness or dizziness, or shortness of breath.
Tafinlar, in combination with Mekinist, can cause new or worsening high blood pressure (hypertension). A patient’s blood pressure should be checked during treatment. Patients should be advised to tell their health care professional if they develop high blood pressure, their blood pressure worsens, or if they have severe headache, lightheadedness, blurry vision, or dizziness.
The most common side effects of Tafinlar, in combination with Mekinist, include fever, rash, nausea, fatigue, headache, chills, diarrhoea, vomiting, high blood pressure (hypertension), joint aches, muscle aches, swelling of the face, arms, or legs, and cough.
Please see full Prescribing Information for Tafinlar and Mekinist.
Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic and biosimilar pharmaceuticals and eye care. Novartis has leading positions globally in each of these areas. In 2017, the Group achieved net sales of USD 49.1 billion, while R&D throughout the Group amounted to approximately USD 9.0 billion. Novartis Group companies employ approximately 124,000 full-time-equivalent associates. Novartis products are sold in approximately 155 countries around the world.
In the UK, Novartis develops, manufactures and markets innovative medicines, devices and diagnostic tests which help improve patient outcomes. Based on four sites across the north and south of England, we employ approximately 1,500 people to serve healthcare needs across the whole of the UK, as well as supporting the global operations of Novartis by manufacturing the active pharmaceutical ingredients used worldwide in many medicines. In 2016 Novartis in the UK invested almost £40million in R&D and is the largest commercial sponsor of clinical trials. For more information, please visit www.novartis.co.uk.