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Old 04-28-2020, 07:59 AM   #1
Lani
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Join Date: Mar 2006
Posts: 4,778
FDA approves tucatinib for Stage 4 her2+ breast cancer

U.S. Food and Drug Administration FDA approves tucatinib for patients with HER2-positive metastatic breast cancer
FDA approves tucatinib for patients with HER2-positive metastatic breast cancer
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On April 17, 2020, the Food and Drug Administration approved (TUKYSA, Seattle Genetics, Inc.) in combination with trastuzumab and capecitabine, for adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. The U.S. FDA, the Australian Therapeutic Goods Administration, Health Canada, Health Sciences Authority (Singapore), and Swissmedic (Switzerland) collaborated on this review.
While the FDA approved tucatinib today, the application is still under review at the
other agencies.

Efficacy was demonstrated in the HER2CLIMB trial (NCT02614794) enrolling 612 patients with HER2-positive metastatic breast cancer who had prior treatment with trastuzumab, pertuzumab, and ado-trastuzumab emtansine. Patients received either tucatinib 300 mg twice daily plus trastuzumab and capecitabine (tucatinib arm, n=410) or placebo plus trastuzumab and capecitabine (control arm, n=202).

The primary endpoint was progression-free survival (PFS), assessed by a blinded independent central review, evaluated in the initial 480 randomized patients. The median PFS in patients receiving tucatinib was 7.8 months (95% CI: 7.5, 9.6) compared to 5.6 months (95% CI: 4.2, 7.1) for patients enrolled on the control arm (HR 0.54; 95% CI: 0.42, 0.71; p<0.00001).

Additional efficacy outcome measures were evaluated in all randomized patients and included overall survival (OS), PFS among patients with a history or presence of brain metastases, and confirmed objective response rate (ORR).

The median OS in patients on the tucatinib arm was 21.9 months (95% CI: 18.3, 31.0) compared to 17.4 months (95% CI: 13.6, 19.9) for patients on the control arm (HR: 0.66; 95% CI: 0.50, 0.87; p=0.00480). The median PFS for patients with baseline brain metastases on the tucatinib arm was 7.6 months (95% CI: 6.2, 9.5) compared to 5.4 months (95% CI: 4.1, 5.7) for those on the control arm (HR: 0.48; 0.34, 0.69; p<0.00001).

The confirmed ORR for patients with measurable disease was 40.6% (95% CI: 35.3, 46.0) and 22.8% (95% CI: 16.7, 29.8) for patients in the tucatinib and control arms, respectively (p=0.00008).

The most common adverse reactions (≥ 20% of patients) were diarrhea, palmar-plantar erythrodysesthesia, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash. Tucatinib can also cause severe diarrhea and hepatotoxicity.

The recommended tucatinib dose is 300 mg taken orally twice a day in combination with trastuzumab (at standard dosage) and capecitabine (1000 mg/m2 given orally twice daily on days 1-14 of a 21-day cycle) until disease progression or unacceptable toxicity.

View full prescribing information for TUKYSA.

This review used the Real-Time Oncology Review (RTOR) pilot program and Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. The FDA approved this application 4 months ahead of the FDA goal date.

FDA granted tucatinib orphan drug, fast track, and breakthrough therapy designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

For information on the COVID-19 pandemic, see the following resources:

FDA: Coronavirus Disease 2019 (COVID-19)
NCI: Coronavirus: What People With Cancer Should Know
CDC: Coronavirus (COVID-19)
Follow the Oncology Center of Excellence on Twitter @FDAOncologyExternal





Content current as of:
04/20/2020

Contact FDA Follow FDA on Facebook Follow FDA on Twitter View FDA videos on YouTube Subscribe to FDA RSS feeds FDA Homepage Contact Number 1-888-INFO-FDA (1-888-463-6332)
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Old 04-29-2020, 06:59 PM   #2
Lani
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Join Date: Mar 2006
Posts: 4,778
Re: FDA approves tucatinib for Stage 4 her2+ breast cancer

Cancer
CancerScope Free Access
Addition of tucatinib to trastuzumab and chemotherapy improves survival for patients with metastatic, HER2‐positive breast cancer
Carrie Printz
First published: 28 April 2020 https://doi-

E
Recent findings published in The New England Journal of Medicine have indicated that the addition of tucatinib to capecitabine and trastuzumab significantly improved progression‐free survival and overall survival in patients with advanced HER2‐positive breast cancer, regardless of whether they had metastatic disease.1 The results, from the HER2CLIMB study, were presented simultaneously at the 2019 San Antonio Breast Cancer Symposium, held December 10 to 14, 2019, in San Antonio, Texas. Tucatinib is a tyrosine kinase inhibitor (TKI) that is highly selective for HER2.

The international randomized trial enrolled 612 patients with locally advanced or metastatic HER2‐positive breast cancer who had received prior treatment with trastuzumab, pertuzumab, and trastuzumab emtansine. The patients were randomly assigned 2:1 to trastuzumab and capecitabine with or without tucatinib. Approximately one‐half of the patients (47%) had brain metastases at baseline.

Lead author Rashmi Murthy, MD, an assistant professor in the Department of Breast Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston, Texas, notes that the trial allowed patients to enroll if they had untreated, treated but stable, or previously treated progressive brain metastases, the latter of which is a common clinical problem for up to one‐half of patients with the disease. She adds that these patients have limited treatment options because the majority of drugs have trouble crossing the blood‐brain barrier.

The study met its primary endpoint and demonstrated that the combination treatment reduced the risk of death by approximately 46% compared with trastuzumab and capecitabine alone. Meeting its secondary endpoints at interim analysis, the trial also showed that adding tucatinib to standard treatment prolonged overall survival, reducing the risk of death by approximately 34% and extending progression‐free survival by 52% in patients with brain metastases. Also, in the tucatinib group, the overall response rate was found to be higher at 41% compared with 23% in the standard‐of‐care treatment group.

The 3‐drug combination had no unexpected toxicities. The most common side effects with tucatinib included diarrhea, fatigue, and vomiting, the majority of which were low grade. The drug discontinuation rate was considered low, at 5.7% in the triplet arm compared with 3% in the standard‐of‐care arm.

The results demonstrate that tucatinib is both safe and effective, according to Dr. Murthy. Furthermore, they indicate that the 3‐drug combination should be the new standard of care for patients who have been pretreated with multiple anti‐HER2 agents, including those individuals with brain metastases. The findings also resulted in unblinding the study so that all patients could receive the new combination treatment. Researchers also planned to submit a new drug application to the US Food and Drug Administration early this year.
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