The U.S. Food and Drug Administration today approved Verzenio (abemaciclib) to treat adult patients who have hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer that has progressed after taking therapy that alters a patient’s hormones (endocrine therapy). Verzenio is approved to be given in combination with an endocrine therapy, called fulvestrant, after the cancer had grown on endocrine therapy. It is also approved to be given on its own, if patients were previously treated with endocrine therapy and chemotherapy after the cancer had spread (metastasized).

“Verzenio provides a new targeted treatment option for certain patients with breast cancer who are not responding to treatment, and unlike other drugs in the class, it can be given as a stand-alone treatment to patients who were previously treated with endocrine therapy and chemotherapy,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

Verzenio works by blocking certain molecules (known as cyclin-dependent kinases 4 and 6), involved in promoting the growth of cancer cells. There are two other drugs in this class that are approved for certain patients with breast cancer, palbociclib approved in February 2015 and ribociclib approved in March 2017.

Breast cancer is the most common form of cancer in the United States. The National Cancer Institute at the National Institutes of Health estimates approximately 252,710 women will be diagnosed with breast cancer this year, and 40,610 will die of the disease. Approximately 72 percent of patients with breast cancer have tumors that are HR-positive and HER2-negative.

The safety and efficacy of Verzenio in combination with fulvestrant were studied in a randomized trial of 669 patients with HR-positive, HER2-negative breast cancer that had progressed after treatment with endocrine therapy and who had not received chemotherapy once the cancer had metastasized. The study measured the length of time tumors did not grow after treatment (progression-free survival). The median progression-free survival for patients taking Verzenio with fulvestrant was 16.4 months compared to 9.3 months for patients taking a placebo with fulvestrant.

The safety and efficacy of Verzenio as a stand-alone treatment were studied in a single-arm trial of 132 patients with HR-positive, HER2-negative breast cancer that had progressed after treatment with endocrine therapy and chemotherapy after the cancer metastasized. The study measured the percent of patients whose tumors completely or partially shrank after treatment (objective response rate). In the study, 19.7 percent of patients taking Verzenio experienced complete or partial shrinkage of their tumors for a median 8.6 months.

Common side effects of Verzenio include diarrhea, low levels of certain white blood cells (neutropenia and leukopenia), nausea, abdominal pain, infections, fatigue, low levels of red blood cells (anemia), decreased appetite, vomiting and headache.

Serious side effects of Verzenio include diarrhea, neutropenia, elevated liver blood tests and blood clots (deep venous thrombosis/pulmonary embolism). Women who are pregnant should not take Verzenio because it may cause harm to a developing fetus.

The FDA granted this application Priority Review and Breakthrough Therapy designations.

The FDA granted the approval of Verzenio to Eli Lilly and Company.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

On Aug. 17, 2017, the U.S. Food and Drug Administration granted regular approval to olaparib tablets (Lynparza, AstraZeneca) for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy.

With the addition of the new indication, a tablet formulation of olaparib is introduced. FDA approved olaparib capsules in 2014 for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. Today, FDA also approved olaparib tablets for this indication. Olaparib tablets and capsules are not interchangeable. Olaparib capsules are being phased out of the U.S. market and will be available only through the Lynparza Specialty Pharmacy Network.

The approval in the maintenance setting was based on two randomized, placebo-controlled, double-blind, multicenter trials in patients with recurrent ovarian cancers who were in response to platinum-based therapy.

SOLO-2 (NCT01874353) randomized 295 patients with recurrent germline BRCA-mutated ovarian, fallopian tube, or primary peritoneal cancer (2:1) to receive olaparib tablets 300 mg orally twice daily or placebo. SOLO-2 demonstrated a statistically significant improvement in investigator-assessed progression-free survival (PFS) in patients randomized to olaparib compared with those who received placebo, with a hazard ratio (HR) of 0.30 (95% CI: 0.22, 0.41; p<0.0001). The estimated median PFS was 19.1 and 5.5 months in the olaparib and placebo arms, respectively.

Study 19 (NCT00753545) randomized 265 patients regardless of BRCA status (1:1) to receive olaparib capsules 400 mg orally twice daily or placebo. Study 19 demonstrated a statistically significant improvement in investigator-assessed PFS in patients treated with olaparib vs. placebo with a HR of 0.35 (95% CI: 0.25, 0.49; p<0.0001). The estimated median PFS was 8.4 months and 4.8 months in the olaparib and placebo arms, respectively.

The most common adverse reactions (≥20%) in clinical trials were anemia, nausea, fatigue (including asthenia), vomiting, nasopharyngitis, diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation, and stomatitis. The most common laboratory abnormalities (≥25%) were decrease in hemoglobin, increase in mean corpuscular volume, decrease in lymphocytes, decrease in leukocytes, decrease in absolute neutrophil count, increase in serum creatinine, and decrease in platelets.

The recommended olaparib tablet dose for both the maintenance therapy and later line treatment setting is 300 mg (two 150 mg tablets) taken orally twice daily with or without food.

Full prescribing information is available at:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208558s000lbl.pdf.

FDA granted this application Fast Track status. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf.

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 by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).

Follow the Oncology Center of Excellence on Twitter @FDAOncology.

Check out recent approvals at the OCE’s new podcast, Drug Information Soundcast in Clinical Oncology (D.I.S.C.O.), available at www.fda.gov/DISCO.

The U.S. Food and Drug Administration today approved Rydapt (midostaurin) for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who have a specific genetic mutation called FLT3, in combination with chemotherapy. The drug is approved for use with a companion diagnostic, the LeukoStrat CDx FLT3 Mutation Assay, which is used to detect the FLT3 mutation in patients with AML.

AML is a rapidly progressing cancer that forms in the bone marrow and results in an increased number of white blood cells in the bloodstream. The National Cancer Institute estimated that approximately 19,930 people would be diagnosed with AML in 2016 and 10,430 were projected to die of the disease.

“Rydapt is the first targeted therapy to treat patients with AML, in combination with chemotherapy,” said Richard Pazdur, M.D., acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research and director of the FDA’s Oncology Center of Excellence. “The ability to detect the gene mutation with a diagnostic test means doctors can identify specific patients who may benefit from this treatment.”

Rydapt is a kinase inhibitor that works by blocking several enzymes that promote cell growth. If the FLT3 mutation is detected in blood or bone marrow samples using the LeukoStrat CDx FLT3 Mutation Assay, the patient may be eligible for treatment with Rydapt in combination with chemotherapy.

The safety and efficacy of Rydapt for patients with AML were studied in a randomized trial of 717 patients who had not been treated previously for AML. In the trial, patients who received Rydapt in combination with chemotherapy lived longer than patients who received chemotherapy alone, although a specific median survival rate could not be reliably estimated. In addition, patients who received Rydapt in combination with chemotherapy in the trial went longer (median 8.2 months) without certain complications (failure to achieve complete remission within 60 days of starting treatment, progression of leukemia or death) than patients who received chemotherapy alone (median three months).

Common side effects of Rydapt in patients with AML include low levels of white blood cells with fever (febrile neutropenia), nausea, inflammation of the mucous membranes (mucositis), vomiting, headache, spots on the skin due to bleeding (petechiae), musculoskeletal pain, nosebleeds (epistaxis), device-related infection, high blood sugar (hyperglycemia) and upper respiratory tract infection. Rydapt should not be used in patients with hypersensitivity to midostaurin or other ingredients in Rydapt. Women who are pregnant or breastfeeding should not take Rydapt because it may cause harm to a developing fetus or a newborn baby. Patients who experience signs or symptoms of lung damage (pulmonary toxicity) should stop using Rydapt.

Rydapt was also approved today for adults with certain types of rare blood disorders (aggressive systemic mastocytosis, systemic mastocytosis with associated hematological neoplasm or mast cell leukemia). Common side effects of Rydapt in these patients include nausea, vomiting, diarrhea, swelling (edema), musculoskeletal pain, abdominal pain, fatigue, upper respiratory tract infection, constipation, fever, headache and shortness of breath.

The FDA granted this application Priority Review, Fast Track (for the mastocytosis indication) and Breakthrough Therapy (for the AML indication) designations.

The FDA granted the approval of Rydapt to Novartis Pharmaceuticals Corporation. The FDA granted the approval of the LeukoStrat CDx FLT3 Mutation Assay to Invivoscribe Technologies Inc.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Related Information

• FDA: Office of Hematology and Oncology Products
• FDA: Approved Drugs: Questions and Answers
• FDA: Fast Track, Breakthrough Therapy, Accelerated Approval, Priority Review
• FDA: Companion Diagnostics
• NCI: Adult AML
• GARD: Systemic mastocytosis

The U.S. Food and Drug Administration today expanded the approved use of Stivarga (regorafinib) to include treatment of patients with hepatocellular carcinoma (HCC or liver cancer) who have been previously treated with the drug sorafenib. This is the first FDA-approved treatment for a liver cancer in almost a decade.

“Limited treatment options are available for patients with liver cancer,” said Richard Pazdur, M.D., acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research and director of the FDA’s Oncology Center of Excellence. “This is the first time patients with HCC have had an FDA-approved treatment that can be used if their cancer has stopped responding to initial treatment with sorafenib.”

According to the National Cancer Institute, approximately 40,710 people will be diagnosed with liver cancers in 2017 and approximately 28,920 will die of these diseases. HCC originates in the liver and is the most common form of liver cancer.

Stivarga is a kinase inhibitor that works by blocking several enzymes that promote cancer growth, including enzymes in the vascular endothelial growth factor pathway. Stivarga is also approved to treat colorectal cancer and gastrointestinal stromal tumors that are no longer responding to previous treatments.

The safety and efficacy of Stivarga for treatment of HCC were studied in a randomized trial of 573 patients with HCC whose tumors had progressed after receiving sorafenib. The trial measured the length of time the patients lived after receiving treatment (overall survival), the length of time tumors did not grow after treatment (progression-free survival) and the percent of patients whose tumors completely or partially shrank after treatment (overall response rate). The median overall survival for patients taking Stivarga was 10.6 months, compared to 7.8 months for patients taking a placebo. The median progression-free survival for patients taking Stivarga was 3.1 months compared to 1.5 months for patients taking a placebo. The overall response rate for patients taking Stivarga was 11 percent, compared to 4 percent of patients taking placebo.

Common side effects of Stivarga include pain (including gastrointestinal and abdominal pain), hand-foot skin reaction, fatigue, diarrhea, decreased appetite, high blood pressure (hypertension), infection, difficulty speaking (dysphonia), high levels of bilirubin in the blood (hyperbilirubinemia), fever, inflammation of the mucous membranes (mucositis), weight loss, rash and nausea. Stivarga is associated with serious risks, including liver damage (hepatotoxicity), infections, heavy bleeding (hemorrhage), holes in the stomach or intestines (gastrointestinal perforation or fistula), skin damage (dermatologic toxicity), hypertension, problems with blood flow to the heart (cardiac ischemia and infarction), temporary brain swelling(reversible posterior leukoencephalopathy syndrome) and wound healing complications.

Women who are pregnant or breastfeeding should not take Stivarga because it may cause harm to a developing fetus or a newborn baby. Women and men who are taking Stivarga should use effective contraception during and for two months after taking the final dose.

This Stivarga application was granted Priority Review designation, under which the FDA’s goal is to take action on an application within six months where the agency determines that the drug, if approved, would significantly improve the safety or effectiveness of treating, diagnosing or preventing a serious condition.

This indication for Stivarga also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The FDA granted the approval of Stivarga to Bayer HealthCare Pharmaceuticals Inc.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

The U.S. Food and Drug Administration today approved Nerlynx (neratinib) for the extended adjuvant treatment of early-stage, HER2-positive breast cancer. For patients with this type of cancer, Nerlynx is the first extended adjuvant therapy, a form of therapy that is taken after an initial treatment to further lower the risk of the cancer coming back. Nerlynx is indicated for adult patients who have been previously treated with a regimen that includes the drug trastuzumab.

“HER2-positive breast cancers are aggressive tumors and can spread to other parts of the body, making adjuvant therapy an important part of the treatment plan,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Now, these patients have an option after initial treatment that may help keep the cancer from coming back.”

Breast cancer is the most common form of cancer in the United States. The National Cancer Institute (NCI) estimates approximately 252,710 women will be diagnosed with breast cancer this year, and 40,610 will die of the disease. According to the NCI, approximately 15 percent of patients with breast cancer have tumors that are HER2-positive.

Nerlynx is a kinase inhibitor that works by blocking several enzymes that promote cell growth.

The safety and efficacy of Nerlynx were studied in a randomized trial of 2,840 patients with early-stage, HER2-positive breast cancer who completed treatment with trastuzumab within the previous two years. The study measured the amount of time after the start of the trial that it took for the cancer to come back or for death to occur from any cause (invasive, disease-free survival). After two years, 94.2 percent of patients treated with Nerlynx had not experienced cancer recurrence or death compared with 91.9 percent of patients receiving placebo.

Common side effects of Nerlynx include diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, swollen and sore mouth (stomatitis), decreased appetite, muscle spasms, indigestion (dyspepsia), liver damage (AST or ALT enzyme increase), nail disorder, dry skin, abdominal swelling (distention), weight loss and urinary tract infection.

Patients should be given loperamide for the first 56 days of treatment with Nerlynx and as needed thereafter to help manage diarrhea. Additional antidiarrheals, fluids and electrolytes should also be given as clinically indicated to help manage diarrhea. Patients who experience severe side effects, including diarrhea or liver damage (hepatotoxicity), should stop taking Nerlynx. Women who are pregnant or breastfeeding should not take Nerlynx because it may cause harm to a developing fetus or a newborn baby.

The FDA granted the approval of Nerlynx to Puma Biotechnology Inc.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.