Adil Daud: July 31, 2019

SUMMER SKIN CANCER ALERT

TREATMENT FOR ADVANCED MELANOMA PATIENTS SHOWS PROMISE IN LANDMARK STUDY

Largest Pooled Analysis of Patients with BRAF-mutated Metastatic Melanoma Recently Published in The New England Journal of Medicine1,2

Increased Chance for 5-Year Survival Reported with Tafinlar® and Mekinist® as Treatment for Advanced Melanoma with BRAF Genetic Mutation1,2

 

 

Adil Daud, MD

Oncologist specializing in melanoma and other skin cancers and co-director, Melanoma Clinical Research, UCSF Helen Diller Family Comprehensive Cancer Center

 

A person diagnosed with stage 4 melanoma 5+ years ago, who has been under Dr. Daud’s care and who has taken the study medication

 

Doctor and patient bring their personal experiences to the discussion. Their story is an empowering one that emphasizes the importance of prevention, diagnosis, genetic mutation testing and being an informed patient when making treatment decisions and managing life after an advanced melanoma diagnosis

 

Melanoma is the most serious and life-threatening type of skin cancer. It is almost always treatable when caught early, but if it metastasizes, or spreads to other parts of the body, it becomes difficult to treat3.

 

At the recent ASCO meeting4, the world’s largest clinical cancer research meeting, researchers reported encouraging news from The New England Journal of Medicine for people with unresectable or metastatic melanoma – the most aggressive form of skin cancer – who have the BRAF genetic mutation1,3.

 

These data support results seen in earlier analyses of patients with advanced melanoma treated with Tafinlar® (dabrafenib) and Mekinist® (trametinib) combination therapy1,2,5,6.

 

With summer comes a heightened awareness of skin cancer. Applying sunscreen, wearing protective clothing, and avoiding tanning beds are all important precautions you can take against the disease7. For those already living with skin cancer, however, this data underscores how important it is that patients with stage III and stage IV melanoma talk to their doctor about getting tested for their BRAF mutation. Knowing their BRAF status is a key piece of information when evaluating all available treatment options1.

 

On July 31st, we invite you to speak to Dr. Adil Daud, co-director, Melanoma Clinical Research, UCSF Helen Diller Family Comprehensive Cancer Center. Dr. Daud did not participate in the published 5-year survival study but he can provide his clinical perspective what it means for patients with advanced melanoma, and why they should talk to their doctors about BRAF testing. He will also offer tips on sun protection, screening, genetic testing and how to be a partner with your doctor.

 

Dr. Daud will be accompanied by one of his patients, who was diagnosed with stage 4 melanoma and has been on the study’s medication for 5 years.

 

Did You Know?

·       Advanced melanoma is different from other skins cancers and can be aggressive and deadly8

·       Nearly 100,000 adults in the United States will be diagnosed with melanoma this year and approximately seven percent will die from melanoma3

·       There are various mutation types within the melanoma family, specifically in the BRAF, NRAS and KIT genes, and it’s important for patients to speak to their doctor to evaluate treatment options9

 

For more information please visit: https://www.us.tafinlarmekinist.com/advanced-melanoma/

 

 About COMBI-d and COMBI-v

Researchers report that overall 1 in 3 (95% CI: 30-38%) patients with Stage IIIC and IV metastatic melanoma in the pooled analysis who were treated with Tafinlar + Mekinist were still alive at five years1,2. These data are noteworthy as previous data estimate the 5-year survival rate for Stage IV metastatic melanoma are lower2,10

 

COMBI-d is a pivotal Phase III randomized, double-blinded study (NCT01584648) comparing the combination of the BRAF inhibitor, Tafinlar, and the MEK inhibitor, Mekinist, to single-agent therapy with Tafinlar and placebo as first-line therapy in patients with unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600E/K mutation-positive cutaneous melanoma.

 

COMBI-v is a two-arm, open-label, Phase III study comparing the combination of Tafinlar + Mekinist with vemurafenib monotherapy in patients with BRAF V600E/K mutation-positive unresectable or metastatic melanoma (NCT01597908). The primary endpoint of this study was OS1.

 

About Tafinlar + Mekinist

Tafinlar + Mekinist target different kinases within the serine/threonine kinase family—BRAF and MEK1/2, respectively—in the RAS/RAF/MEK/ERK pathway, which is implicated in melanoma and NSCLC, among other cancers. When Tafinlar is used with Mekinist, the combination has been shown to slow tumor growth more than either drug alone.

 

Tafinlar + Mekinist have been investigated for the treatment of a variety of cancers as part of an ongoing clinical trial program. Tafinlar + Mekinist are approved in more than 60 countries, for uses including:

 

INDICATIONS

TAFINLAR® (dabrafenib) capsules, in combination with MEKINIST® (trametinib) tablets, is indicated:

  • for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test
  • for the adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection
  • for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation as detected by an FDA-approved test

Limitations of Use: TAFINLAR is not indicated for the treatment of patients with wild-type BRAF melanoma or wild-type BRAF NSCLC. MEKINIST is not indicated for the treatment of patients with melanoma who have progressed on prior BRAF-inhibitor therapy.

Approved indications vary worldwide. Please refer to local labeling for indication language in a particular country. 

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 provider immediately for a new wart, skin sore, or bump that bleeds or does not heal, or a change in the size or color of a mole.

 

When Tafinlar is used in combination with Mekinist, it can cause serious bleeding problems, especially in the brain or stomach that can lead to death. Patients should be advised to call their health care provider 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 provider immediately if they have any of the following symptoms: bleeding, diarrhea (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 provider 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 provider right away if they get: blurred vision, loss of vision, or other vision changes, seeing color 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 provider 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 provider right away 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 provider 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 provider 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 provider 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 anemia called hemolytic anemia, where the body does not have enough healthy red blood cells. Patients should be advised to tell their health care provider 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 provider 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, diarrhea, 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.

 References:

1.     Paul D. Nathan, et al. Five-year analysis of dabrafenib plus trametinib (D+T) in patients with BRAF V600–mutant unresectable or metastatic melanoma confirms long-term benefit. Abstract #9507. 2019 American Society of Clinical Oncology Annual Meeting, May 31-June 4, Chicago, IL.

2.     Robert C, et al. N Engl J Med. 2019 June 4. doi: 10.1056/NEJMoa1904059. [Epub ahead of print].

3.     Melanoma. Skin Cancer Foundation. Available at: https://www.skincancer.org/skin-cancer-information/melanoma. Accessed May 17, 2019

4.     American Society of Clinical Oncology (2019, April 17). ASCO Announces Top Studies to Be Presented at 2019 Annual Meeting [Press release]. Retrieved from https://www.asco.org/about-asco/press-center/news-releases/asco-announces-top-studies-be-presented-2019-annual-meeting.

5.     Robert. C, Karaszewska b, Schachter J, et al. Three-year estimate of overall survival in COMBI-v, a randomized phase 3 study evaluating first-line dabrafenib (D) + trametinib (T) in patients (pts) with unresectable or metastatic BRAF V600E/K-mutant cutaneous melanoma. Abstract #LBA40. 2016 European Society of Medical Oncology (ESMO) Annual Meeting, Copenhagen, Denmark

6.     Flaherty, K.T. Genomic Analysis and 3-Year Efficacy and Safety Update of COMBI-d, a phase 3 study of dabrafenib + trametinib vs dabrafenib monotherapy in patients with unresectable or metastatic BRAF V600E/K–mutant cutaneous melanoma. Abstract #9502. 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, USA

7.     Lazovich D, et. al. Time to get serious about skin cancer prevention. Cancer Epidemiol Biomarkers Prev. 2012;21(11):1893–1901.

8.     Key Statistics for Melanoma Skin Cancer. American Cancer Society. Available at https://www.cancer.org/cancer/melanoma-skin-cancer/about/key-statistics.html. Accessed May 17, 2019.

9.     Schandendorf D, et al. Melanoma. Nature reviews Disease Primers. 2015.

10.  Survival Rates for Melanoma Skin Cancer. American Cancer Society. Available at

https://www.cancer.org/cancer/melanoma-skin-cancer/detection-diagnosis-staging/survival-rates-for-melanoma-skin-cancer-by-stage.html. Accessed May 17, 2019.

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