Oncology Drug Shortage Update

Home , Dabrafenib, Trametinib

] ] [ News ] Analysis ] Commentary ] Controversy ] June 25, 2013 Vol. 35 No. 12 oncology-times.com Oncology 5 Years 3 of g P in u t b a l r

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e g imes C 35 TThe Independent Hem/Onc News Source

Oncology Drug Shortage Update

BY HEATHER LINDSEY

new survey documents that cancer drug shortages have occurred A frequently, led to treatment delays, increased the risks of errors and adverse outcomes, complicated research, and increased the costs of medications. The survey, by the Hematology-Oncology Pharmacy Association, is the first to focus specifically on oncology. Page 14

• Advanced NSCLC: 60 Gy Standard • Seminoma: Opting Out of Adjuvant Therapy Safe Lung Cancer: • Immunotherapy ‘Poised to Change Treatment Paradigm’ Leukemia Researcher Lukas Meeting Spotlights • DLBCL: CT Surveillance Adds Little Value Wartman Describes 10-Year Progress in Molecularly • CLL: Enthusiasm for Idelalisb Personal Battle Against Guided Therapy p.10 • Fitness & Cancer Prognosis pp.18, 25, 28, 33, 36, 37 Adult ALL p.20

[ALSO] SHOP TALK ��3 EDITH PEREZ: How I Treat Patients with Advanced HER2-Positive Breast Cancer ��5 Exercise, Estrogen, & Breast Cancer Risk: New Data ��11 JOE SIMONE: Changing Views of Leaders and Leadership ��16 Science Symposium for ACS’s 100th Anniversary ��24 GEORGE SLEDGE: On Buildings ��32 Stronger ‘Alliance’ Leads to Better Compliance, Enhanced Well-Being ��34 POETRY by Cancer Caregivers ��40

@OncologyTimes /OncologyTimesNews Periodicals 6

FDA Approves Two Drugs for Advanced Melanoma—Tafinlar and Mekinist—and Companion Diagnostic he U.S. Food and Drug Pazdur, MD, Director of the Office of tension, shaking chills, dehydration, heart failure, lung inflammation, TAdministration approved two Hematology and Oncology Products in kidney failure, and increased blood skin infections, and loss of vision. new oral agents, Tafinlar (dabrafenib) the FDA’s Center for Drug Evaluation sugar levels requiring medication. Common reported side effects were and Mekinist (trametinib), for pa- and Research, said in a news release. The most common side effects re- rash, diarrhea, peripheral edema, tients with metastatic or unresect- Both vemurafenib (OT, 9/10/11 issue) ported in patients receiving the drug and acne-like skin breakouts. oncology-times.com

able melanoma. and ipilimumab (OT, 4/25/13 issue) were hyperkeratosis, headache, fever, Women of childbearing years • Tafinlar, a BRAF inhibitor, is were approved in 2011 for the treat- joint pain, non-cancerous skin tumors, should be advised that tafinlar and approved to treat patients with ment of patients with metastatic or un- hair loss, and hand-foot syndrome. mekinist carry the potential to cause melanoma whose tumors express resectable melanoma. fetal harm. Men and women should the BRAF V600E gene muta- Mekinist (Trametinib) also be advised that both agents also tion. Mekinist, a MEK inhibitor, is Tafinlar (Dabrafenib) The approval for mekinist is based carry the potential to cause infertility. approved to treat patients whose The approval for tafinlar is based on on a study of 322 patients with met- The FDA’s approval of the THxID tumors express the BRAF V600E or a study of 250 previously untreated astatic or unresectable melanoma BRAF test is based on data from june 25, 2013

V600K gene mutations. adult patients with BRAF V600E with the BRAF V600E or V600K gene clinical studies that support the tafin- • The FDA approved both drugs gene mutation-positive metastatic mutation, who had no more than lar and mekinist approvals. Samples as single agents, not combination or unresectable melanoma. Patients one prior chemotherapy regimen of patients’ melanoma tissue were treatment, along with a genetic test, were randomly for advanced or collected to test for the mutation. the THxID BRAF test, which is a com- assigned to re- metastatic dis- Both drugs are marketed by panion diagnostic that will help de- ceive tafinlar or ease and no prior GlaxoSmithKline. The THxID BRAF termine if a patient’s melanoma cells the chemother- BRAF or MEK in- Kit is manufactured by bioMérieux have the V600E or V600K mutation apy drug dacar- hibitor treatment. of Grenoble, France.

oncology times in the BRAF gene. Approximately bazine. The study Patients were Tim Turnham, Executive Director 76,690 Americans will be diagnosed demonstrated a randomly as- of the Melanoma Research with melanoma in 2013, according statistically sig- signed to receive Foundation, said in a statement that to the National Cancer Institute, and nificant increase in progression-free either mekinist or chemotherapy. the organization celebrates the ap- approximately half of skin melano- survival for patients receiving tafinlar Median progression-free survival provals, as there is a dire need for mas have a BRAF mutation. compared with patients taking da- in patients treated with mekinist new treatment options for people “Advancements in our understand- carbazine—median progression-free was 4.8 months compared with 1.5 with the disease. “This is positive ing of the biological pathways of a survival was 5.1 months compared months for the chemotherapy group. news for the melanoma community. disease have allowed for the devel- with 2.7 months, respectively. Patients who previously used tafinlar We still have much work to do in opment of Tafinlar and Mekinist, the The most serious side effects re- or other inhibitors of BRAF did not terms of providing additional treat- third and fourth drugs the FDA has ported were: increased risk of cutane- appear to benefit from mekinist. The ments for people fighting advanced approved for treating metastatic mela- ous squamous cell carcinoma, fevers most serious side effects reported in melanoma, but this is an important O noma in the past two years,” Richard that may be complicated by hypo- patients receiving the drug included step forward.” T

➞PEREZ recommended. If tumor progression oc- Additionally, the objective response months in the combination arm compared continued from page 5 curs, then second-line therapy including rate was higher with T-DM1 than with with the lapatinib-alone arm. an anti-HER2 agent is recommended. the double-agent combination (43.6% vs. The challenge with applying these data The FDA has approved T-DM1 (now 30.8%; P<0.001). The two-year overall to practice is that lapatinib alone is not known as ado-trastuzumab emtansine) for survival rates also favored T-DM1 over the usual comparator we would use in tri- patients with previously treated HER2- lapatinib plus capecitabine (65.4% vs. als or clinical care. Data of pertuzumab positive metastatic breast cancer. T-DM1 47.5%). Perhaps as relevant is that pa- with trastuzumab/chemotherapy or even “There has been is now approved for use as a single agent tients receiving T-DM1 experienced sig- T-DM1 plus pertuzumab/chemotherapy for the treatment of patients with HER2+, nificantly fewer severe side effects than are awaited in the refractory setting, so that a revolution of metastatic breast cancer who previously re- those receiving lapatinib and capecitabine. we can determine how to potentially incor- ceived trastuzumab and a taxane, separately In the second-line setting, clinical data porate pertuzumab beyond the first-line improvements or in combination. Patients should have confirm that HER2 remains a valid target. setting. There is also interest in evaluat- in therapies for either received prior therapy for metastatic Therapeutic options beyond T-DM1 include ing other targeted agents with anti-HER2 disease or developed disease recurrence dur- the combinations of lapatinib/capecitabine, therapies (in the first-line and refractory patients with HER2+ ing or within six months of completing ad- trastuzumab/capecitabine, and lapatinib/ settings), which could help expand the juvant therapy. trastuzumab. Based on the updated final therapeutic options for our patients. metastatic breast T-DM1 combines the anti-HER2 analysis of the EGF104900 study, there In summary, there has been a revolution cancer over the last monoclonal antibody trastuzumab with was a significant .4 5-month median overall of improvements in therapies for patients the chemotherapy DM1, and is the survival advantage with the combination of with HER2+ metastatic breast cancer over 15 years, a result first approved antibody-drug conjugate lapatinib and trastuzumab in patients with the last 15 years. These improvements are a (ADC) for management of breast cancer. heavily pretreated HER2-positive metastatic result of application of biological and clini- of application of So technically, T-DM1 could be appro- breast cancer compared with lapatinib alone. cal trial principles, patient participation in biological and clinical priate as first-line therapy for patients Nearly 300 women participated in this trial, studies, and the development of novel tar- who develop tumor progression within and Blackwell et al found that improvements geted agents that improve survival. trial principles, six months of trastuzumab-containing in absolute overall survival rates were 10 Although more work remains to be done, O adjuvant therapy. percent at six months and 15 percent at 12 the progress has been remarkable. T patient participation The recent regulatory agency approval in studies, and the of T-DM1 was based on the Phase III EMILIA trial, which demonstrated an im- Comments, Questions? development of novel proved median survival of nearly six months in patients with previously treated HER2+ targeted agents that metastatic breast cancer who received dd your comments in the blog version of this article— improve survival.” T-DM1 vs. lapatinib and capecitabine (me- Ahttp://bitly.com/OT-TREAT-Perez—or email dian overall survival was 30.9 months vs. [email protected] 25.1 months, respectively).