EAST HANOVER, N.J., May 31, 2015 /PRNewswire/ — Novartis now announced information from a Phase III COMBI-d investigate display a poignant participation advantage for patients with BRAF V600E/K mutation-positive metastatic cancer when treated with a multiple of Tafinlar® (dabrafenib) and Mekinist® (trametinib) compared to Tafinlar monotherapy alone. This is a initial multiple of BRAF/MEK inhibitors to denote a statistically poignant altogether participation advantage for this studious race in dual Phase III studies. Results are being presented now during a 51st Annual Meeting of a American Society of Clinical Oncology (ASCO) in Chicago.
“This final investigate from COMBI-d confirms before formula display a statistically poignant alleviation in altogether participation among patients with BRAF V600E/K mutation-positive metastatic cancer receiving a multiple of dabrafenib and trametinib compared to dabrafenib monotherapy,” pronounced Georgina Long, B.Sc., Ph.D., M.B.B.S., F.R.A.C.P., medical oncologist, Melanoma Institute Australia, The University of Sydney. “These commentary serve strengthen a motive for a diagnosis of metastatic cancer with this combination.”
The final investigate enclosed a 423 patients enrolled in COMBI-d and showed that a multiple of Tafinlar and Mekinist achieved a statistically poignant altogether participation (OS) advantage compared to Tafinlar monotherapy (median of 25.1 months vs 18.7 months)1. The investigate for a multiple also showed median progression-free participation (PFS) of 11.0 months, altogether response rate (ORR) of 69%, and median generation of response (DoR) of 12.9 months1. The reserve formula were unchanging with a form celebrated to date for a multiple and unchanging with a form celebrated for Tafinlar monotherapy; no new reserve concerns were observed1. The many common inauspicious events (=20%) in a multiple arm were pyrexia, fatigue, nausea, headache, chills, diarrhea, rash, corner pain (arthralgia), hypertension, vomiting, cough and marginal edema1.
“We are really gratified to have entered into a new illness area with a merger of dual medicines that are creation a certain impact on a lives of people with this critical form of skin cancer,” pronounced Bruno Strigini, President, Novartis Oncology. “These COMBI-d information infer that these medicines can significantly extend a lives of people with BRAF V600E/K mutation-positive melanoma, and we are unapproachable to be partial of a swell in this disease.”
In further to formula from a COMBI-d study, long-term information from a Phase I-II investigate showed a three-year OS rate of 38% (95% CI, 25%, 51%) after diagnosis with a multiple of Tafinlar and Mekinist in all patients with BRAF V600E/K mutation-positive metastatic melanoma. Safety formula from this investigate were unchanging with those celebrated in other trials evaluating a combination.
Other information being presented during a meeting, including verbal presentations associated to a investigational use of dabrafenib and trametinib, embody studies in BRAF V600E-mutated metastatic colorectal cancer (CRC), non-small dungeon lung cancer (NSCLC), and other singular cancers.
The formula from a COMBI-d investigate are also being published online in The Lancet on May 31.
About a COMBI-d Study
COMBI-d is a pivotal Phase III randomized, double-blinded investigate (NCT01584648) comparing a multiple of a BRAF inhibitor, Tafinlar, and a MEK inhibitor, Mekinist, to singular representative therapy with Tafinlar and remedy in patients with unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600E/K mutation-positive cutaneous melanoma. The investigate randomized 423 patients from inquisitive sites in Australia, Europe and North and South America. The primary endpoint of this investigate was investigator-assessed PFS. Secondary endpoints enclosed OS, ORR, DoR, and safety. There was no crossover between diagnosis arms.
The final OS investigate showed that a multiple of Tafinlar and Mekinist achieved a statistically poignant OS advantage compared to Tafinlar monotherapy (median of 25.1 months vs 18.7 months; Hazard Ratio [HR] 0.71 [95% Confidence Interval (CI), 0.55-0.92], p=0.011). A 33% rebate in a risk of course or genocide was demonstrated with a multiple therapy compared to monotherapy (median PFS of 11.0 months in a 211 patients receiving multiple therapy vs 8.8 months in a 212 patients receiving monotherapy; HR 0.67 [95% CI, 0.53-0.84], p0.001). The multiple achieved ORR of 69% compared to 53% for monotherapy [difference=15% (95% CI, 6.0%-24.5%), p=0.001]. The median DoR for a 144 responders receiving multiple therapy was 12.9 months [95% CI, 9.4-19.5] compared to 10.6 months in a 113 responders receiving monotherapy [95% CI, 9.1-13.8].
The reserve formula were unchanging with a form celebrated to date for a multiple and unchanging with a form celebrated for Tafinlar monotherapy; no new reserve concerns were observed. The many common inauspicious events (=20%) in a multiple arm were pyrexia, fatigue, nausea, headache, chills, diarrhea, rash, corner pain (arthralgia), hypertension, vomiting, cough and marginal edema1. More patients had AEs heading to sip modifications in a multiple arm compared to Tafinlar monotherapy. Increased occurrence (57% vs 33%) and astringency (grade 3, 7% (n=15) vs 2% (n=4)) of pyrexia occurred with multiple diagnosis as compared to Tafinlar monotherapy. There was a reduce occurrence of cutaneous squamous dungeon carcinoma (cuSCC) including keratoacanthoma with a multiple arm (3% (n=6)) compared to a Tafinlar monotherapy arm (10% (n=22)). Discontinuation of diagnosis due to inauspicious events occurred in 11% (n=24) vs 7% (n=14) of patients in a multiple organisation and a monotherapy group, respectively.
Completion of COMBI-d is a post-marketing requirement for a FDA’s accelerated capitulation for a multiple in a US.
About Tafinlar and Mekinist Combination
Tafinlar and Mekinist aim dual opposite serine/threonine kinases – BRAF and MEK, respectively – in a RAS/RAF/MEK/ERK pathway, that is concerned in NSCLC and melanoma, among other cancers. When Mekinist is used with Tafinlar, a multiple has been shown to delayed expansion growth some-more effectively compared with possibly drug alone. The multiple of Tafinlar and Mekinist is now being investigated in an ongoing clinical hearing module conducted in investigate centers worldwide.
In 2015, Novartis, as inheritor in seductiveness to GlaxoSmithKline, purchased a worldwide disdainful rights to develop, manufacture, and commercialize trametinib, from Japan Tobacco Inc. (JT). JT retains co-promotion rights in Japan.
Tafinlar and Mekinist are purebred trademarks of Novartis Pharma AG. The reserve and efficiency form of a Tafinlar and Mekinist multiple has not nonetheless been determined outward a authorized indication.
Tafinlar and Mekinist Combination Important Safety Information
Tafinlar and Mekinist multiple might means critical side effects, such as:
When Tafinlar is used in multiple with Mekinist, or when Tafinlar is administered as monotherapy, it can means new cancers (both skin cancer and non-skin cancer). Patients should be suggested to hit their alloy immediately for any new lesions, changes to existent lesions on their skin, or signs and symptoms of other Malignancies.
Before holding Tafinlar in multiple with Mekinist, doctors should exam their patients for BRAF wild-type melanoma, as patients but BRAF turn and with RAS turn can be during risk of increasing dungeon proliferation in a participation of a BRAF inhibitor.
When Tafinlar is used in multiple with Mekinist, it can boost a occurrence and astringency of bleeding, and in some cases can lead to death. Patients should be suggested to call their medical provider and get medical assistance right divided if they have headaches, dizziness, or feel weak, cough adult blood or blood clots, puke blood or their puke looks like “coffee grounds,” have red or black stools that demeanour like tar, or any surprising signs of bleeding.
Tafinlar, in multiple with Mekinist, can means blood clots in a arms or legs, that can transport to a lungs and can lead to death. Patients should be suggested to get medical assistance right divided if they have a following symptoms: chest pain, remarkable crispness of exhale or difficulty breathing, pain in their legs with or but swelling, flourishing in their arms or legs, or a cold or dark arm or leg.
Tafinlar in multiple with Mekinist can means heart problems, including heart failure. A patient’s heart duty should be checked before and during treatment. Patients should be suggested to call their medical provider right divided if they have any of a following signs and symptoms of a heart problem: feeling like their heart is pulsation or racing, crispness of breath, flourishing of their ankles and feet, or feeling lightheaded.
Tafinlar alone, or in multiple with Mekinist, can means critical eye problems that can lead to blindness. Patients should be suggested to call their medical provider right divided if they get these symptoms of eye problems: confused vision, detriment of vision, or other prophesy changes, saying tone dots, halo (seeing confused outline around objects), eye pain, swelling, or redness.
Patients should forewarn their alloy if they knowledge any new or worsening symptoms of lung or respirating problems, including crispness of exhale or cough.
Tafinlar alone or in multiple with Mekinist can means fever, that might be serious. When holding Tafinlar in multiple with Mekinist, heat might occur some-more mostly or might be some-more severe. In some cases, chills or jolt chills, too many liquid detriment (dehydration), low blood pressure, dizziness, or kidney problems might occur with a fever. Patients should be suggested to call their medical provider right divided if they get a heat above 38.5 degrees C (101.3 degrees F) while holding Tafinlar.
Rash is a common side outcome of Tafinlar alone, or when used in multiple with Mekinist. Tafinlar alone, or in multiple with Mekinist, can also means other skin reactions. In some cases these rashes and other skin reactions can be severe, and might need to be treated in a hospital. Patients should be suggested to call their medical provider if they get any of a following symptoms: skin unreasonable that bothers them or does not go away, acne, redness, swelling, peeling, or love of hands or feet, skin redness.
Some people might rise high blood sugarine or worsening diabetes during diagnosis with Tafinlar, alone or in multiple with Mekinist. For patients who are diabetic, their medical provider should check their blood sugarine levels closely during treatment. Their diabetes medicine might need to be changed. Patients should be suggested to tell their medical provider if they have any of a following symptoms of critical high blood sugar: increasing lust or urinating some-more mostly than normal, or urinating an increasing volume of urine.
Tafinlar might means healthy red blood cells to mangle down too early in people with G6PD deficiency. This might lead to a form of anemia called hemolytic anemia where a physique does not have adequate healthy red blood cells. Patients should be suggested to tell their medical provider if they have any of a following signs or symptoms of anemia or relapse of red blood cells: yellow skin (jaundice), debility or dizziness, or crispness of breath.
Tafinlar and Mekinist both can means mistreat to an unborn baby when taken by a profound wOman. Tafinlar can also describe hormonal contraceptives ineffective.
The many common side effects of Tafinlar and Mekinist multiple embody fever, nausea, tiredness, rash, chills, diarrhea, headache, vomiting, hypertension, corner pain, marginal edema and cough. The occurrence and astringency of heat is increasing when Mekinist is used in multiple with Tafinlar.
Patients should tell their alloy of any side outcome that bothers them or does not go away. These are not all of a probable side effects of Tafinlar and Mekinist combination. For some-more information, patients should ask their alloy or pharmacist.
Patients should take Tafinlar and Mekinist multiple accurately as their health caring provider tells them. Patients should not change their sip or stop holding Tafinlar and Mekinist multiple unless their health caring provider advises them to. Mekinist should be taken usually once daily (either in a morning or evening, during a same time as Tafinlar). The initial and second sip of Tafinlar should be taken approximately 12 hours apart. Patients should take Tafinlar and Mekinist during slightest 1 hour before or 2 hours after a meal. Do not take a missed sip of Tafinlar within 6 hours of a subsequent sip of Tafinlar. Do not open, crush, or mangle Tafinlar capsules. Do not take a missed sip of Mekinist within 12 hours of a subsequent sip of Mekinist.
Please see full Prescribing Information for Tafinlar and Mekinist.
The foregoing recover contains forward-looking statements that can be identified by difference such as “can,” “investigational,” “being investigated,” “post-marketing requirement,” “ongoing,” or identical terms, or by demonstrate or pragmatic discussions per intensity new indications or labeling for Tafinlar and Mekinist, or per intensity destiny revenues from Tafinlar and Mekinist. You should not place undue faith on these statements. Such forward-looking statements are formed on a stream beliefs and expectations of supervision per destiny events, and are theme to poignant famous and different risks and uncertainties. Should one or some-more of these risks or uncertainties materialize, or should underlying assumptions infer incorrect, tangible formula might change materially from those set onward in a forward-looking statements. There can be no pledge that Tafinlar and Mekinist will be submitted or authorized for any additional indications or labeling in any market, or during any sold time. Nor can there be any pledge that Tafinlar and Mekinist will be commercially successful in a future. In particular, management’s expectations per Tafinlar and Mekinist could be influenced by, among other things, a uncertainties fundamental in investigate and development, including astonishing clinical hearing formula and additional investigate of existent clinical data; astonishing regulatory actions or delays or supervision law generally; a company’s ability to obtain or say exclusive egghead skill protection; ubiquitous mercantile and attention conditions; tellurian trends toward health caring cost containment, including ongoing pricing pressures; astonishing production issues, and other risks and factors referred to in Novartis AG’s stream Form 20-F on record with a US Securities and Exchange Commission. Novartis is providing a information in this press recover as of this date and does not commence any requirement to refurbish any forward-looking statements contained in this press recover as a outcome of new information, destiny events or otherwise.
Novartis Pharmaceuticals Corporation researches, develops, manufactures and markets innovative medicines directed during improving patients’ lives. We offer a extended operation of medicines for cancer, cardiovascular disease, endocrine disease, inflammatory disease, spreading disease, neurological disease, organ transplantation, psychiatric disease, respiratory illness and skin conditions. The company’s goal is to urge people’s lives by pioneering novel medical solutions.
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