FDA Actions & Updates

The latest approvals, designations, and new indications from the U.S. Food and Drug Administration for oncology drugs.

Wednesday, February 14, 2018

Apalutamide has become the first FDA-approved treatment for non-metastatic, castration-resistant prostate cancer.

“This approval is the first to use the endpoint of metastasis-free survival, measuring the length of time that tumors did not spread to other parts of the body or that death occurred after starting treatment,” said Richard Pazdur, MD, 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. “In the trial supporting approval, apalutamide had a robust effect on this endpoint. This demonstrates the agency’s commitment to using novel endpoints to expedite important therapies to the American public."

According to the NCI, prostate cancer is the second most common form of cancer in men in the U.S. The NCI estimates approximately 161,360 men were diagnosed with prostate cancer in 2017, and 26,730 were expected to die of the disease. Approximately 10-20 percent of prostate cancer cases are castration-resistant, and up to 16 percent of these patients show no evidence that the cancer has spread at the time of the castration-resistant diagnosis.

Apalutamide works by blocking the effect of androgens on the tumor. These androgens, such as testosterone, can promote tumor growth. 

The safety and efficacy of apalutamide was based on a randomized clinical trial of 1,207 patients with non-metastatic, castration-resistant prostate cancer. Patients in the trial either received apalutamide or a placebo. All patients were also treated with hormone therapy, either with gonadotropin-releasing hormone (GnRH) analog therapy or with surgery to lower the amount of testosterone in their body (surgical castration). The median metastasis-free survival for patients taking apalutamide was 40.5 months compared to 16.2 months for patients taking a placebo.

Common side effects of apalutamide include fatigue, hypertension, rash, diarrhea, nausea, weight loss, arthralgia, falls, hot flush, decreased appetite, fractures, and peripheral edema. Severe side effects include falls, fractures, and seizures.

​This application was granted Priority Review, under which the FDA’s goal is to take action on an application within 6 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.


Tuesday, February 13, 2018

The FDA has granted pre-market approval for the BD Onclarity HPV assay. The test detects 14 types of high-risk human papillomavirus (HPV) from specimens collected for cervical cancer screening in the BD SurePath liquid based cytology vial.

The assay also identifies HPV genotypes 16, 18, and 45, which are associated with the majority of cervical cancers worldwide, and are disproportionally responsible for up to 94 percent of glandular cervical cancer cases. In evaluating the test, the FDA reviewed data collected during a multi-year, prospective, multi-center clinical trial conducted in the U.S. that included more than 33,500 vaccinated and non-vaccinated women.

It may be used in accordance with clinical guidelines for cervical cancer screening and management to identify the presence of high-risk HPV types. The test is clinically validated for use as a primary screening test, for triaging patients with abnormal Pap test results, and to be used in combination with a Pap test. The assay provides information that together with the physician's assessment and professional guidelines, may be used to inform clinical decision-making.  

"The approval of the [HPV assay] provides clinicians and laboratories an FDA-approved option for HPV primary screening with the liquid based cytology vial," noted Thomas C. Wright, Jr., MD, Professor Emeritus of Pathology and Cell Biology at Columbia University. "The BD Onclarity HPV assay also aligns with clinical screening guidelines from the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology."

The assay is performed on the BD Viper LT system, a bench top molecular platform which automates sample processing and is also FDA-cleared for chlamydia and/or gonorrhea infection testing. 


Thursday, February 8, 2018

The FDA has approved a new indication for abiraterone acetate in combination with prednisone for the treatment of patients with metastatic high-risk castration-sensitive prostate cancer (CSPC). The approval is based on phase III data from the pivotal LATITUDE clinical trial, which found that in patients with metastatic high-risk CSPC, abiraterone acetate in combination with prednisone reduced the risk of death by 38 percent compared to placebos.

"LATITUDE was a large global trial which produced impressive and clinically significant results in overall survival," said Karim Fizazi, MD, PhD, Principal Investigator and Head of the Medical Oncology Department at Institute Gustave Roussy, Villejuif, France. "With today's approval, abiraterone acetate plus prednisone could become a standard of care for patients with metastatic high-risk castration-sensitive prostate cancer."

LATITUDE was a multinational, multicenter, randomized, double-blind, placebo-controlled clinical trial that examined the use of abiraterone acetate 1,000 mg once daily in combination with prednisone 5 mg once daily, compared to placebos in patients with newly diagnosed, metastatic high-risk CSPC, who had not received prior cytotoxic chemotherapy. 

The study enrolled 1,199 patients and was conducted at 235 sites in 34 countries in Europe, Asia-Pacific, Latin America, and Canada. A total number of 597 patients were randomized to receive abiraterone acetate plus prednisone, while 602 patients were randomized to receive placebo. All the patients received a gonadotropin-releasing hormone (GnRH) analog or had prior bilateral orchiectomy. The study data were presented at the plenary session of the 2017 ASCO Annual Meeting, and simultaneously published in The New England Journal of Medicine (2017; 377:352-360).

 The study showed abiraterone acetate in combination with prednisone reduced the risk of death by 38 percent compared to placebos (median OS not estimable vs. 34.7 months, respectively; hazard ratio (HR)=0.62; 95% confidence interval (CI): [0.51, 0.76], p<0.0001). Additional data demonstrated statistically significant delay in time to initiation of chemotherapy for patients in the abiraterone acetate arm compared to those in the placebo arm (median time to initiation of chemotherapy not reached vs. 38.9 months, respectively; HR=0.44; 95% CI: [0.35, 0.56], p < 0.0001).

High-risk disease was defined as having at least two of three risk factors at baseline: a total Gleason score of ≥8, presence of ≥3 lesions on bone scan, and evidence of measurable visceral metastases. Patients with significant cardiac, adrenal, or hepatic dysfunction were excluded. The median duration of treatment with abiraterone acetate and prednisone was 24 months.

The most common adverse reactions (≥10%) that occurred more commonly (>2%) in the abiraterone acetate arm from an analysis of pooled safety data were fatigue, arthralgia, hypertension, nausea, edema, hypokalemia, hot flush, diarrhea, vomiting, upper respiratory infection, cough, and headache.

Metastatic castration-sensitive prostate cancer (CSPC), also referred to as metastatic hormone-sensitive prostate cancer (HSPC) in literature, refers to prostate cancer that still responds to testosterone suppression therapy. Patients with newly-diagnosed metastatic disease and high-risk disease characteristics tend to have a poorer prognosis.

Since its first approval in the U.S. in 2011, abiraterone acetate has been approved in combination with prednisone or prednisolone, in 105 countries. More than 330,000 patients worldwide, including 113,000 in the U.S., have received treatment with it, and it was the number one prescribed oral medication in the U.S. for patients with metastatic CRPC in 2016. 


Friday, January 26, 2018

The FDA has approved the new drug application (NDA) for lutetium Lu 177 dotatate for the treatment of somatostatin receptor positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults.

Lutetium Lu 177 dotatate, which received orphan drug designation from the FDA, is a first-in-class drug and the first available FDA-approved Peptide Receptor Radionuclide Therapy (PRRT), a form of targeted treatment comprising a targeting molecule that carries a radioactive component.

NETs are rare tumors originating in the neuroendocrine cells of numerous organs, including the gastrointestinal tract, pancreas and lung. Some patients develop symptoms arising from the excessive production of hormones by neuroendocrine tumor cells, while others remain clinically silent for years. The estimated incidence, or rate of new cases of NETs, in the U.S. is approximately 6.98/100,000 per year, while the estimated prevalence for 2014, based on the NCI's SEER database, was 171,321. Patient survival with advanced GEP-NETs depends on stage and histology. Patients with well- and moderately-differentiated tumors and distant metastases have a 5-year survival probability of 35 percent.

The approval of lutetium Lu 177 dotatate is based on results of a randomized pivotal phase III study, NETTER-1 that compared treatment using lutetium Lu 177 dotatate plus best standard of care (octreotide LAR 30mg every 4 weeks) to 60 mg of octreotide LAR alone (also dosed every 4 weeks) in patients with inoperable midgut NETs progressing under standard dose octreotide LAR treatment and overexpressing somatostatin receptors, as well as a subset of efficacy and safety data from an international, single-institution, single-arm, open-label trial conducted by Erasmus Medical Center in Rotterdam, Netherlands in more than 1,200 patients with somatostatin receptor positive tumors.

Jonathan Strosberg, MD, Associate Professor, Section Head, Neuroendocrine Tumor Program at Moffitt Cancer Center, and NETTER-1 lead investigator, commented, "There are very few effective treatment options for patients with inoperable, advanced GEP-NETs who are progressive on somatostatin analogues. As a medical oncologist seeing more than 500 patients with NETs each year, I am grateful to have another tool in my arsenal."

The NETTER-1 study met its primary endpoint, showing a 79 percent reduction in risk of disease progression or death in the lutetium Lu 177 dotatate arm compared to the 60 mg octreotide LAR arm (hazard ratio 0.21, 95% CI: 0.13-0.32; p<0.0001). Median PFS was not reached in the lutetium Lu 177 dotatate arm compared to 8.5 months for the 60 mg octreotide LAR arm. A pre-planned interim overall survival analysis determined that lutetium Lu 177 dotatate treatment lead to a 48 percen reduction in the estimated risk of death (hazard ratio 0.52, 95% CI: 0.32-0.84) compared to treatment with 60 mg octreotide LAR. The objective response rate, composed of complete and partial responses, was 13 percent for the lutetium Lu 177 dotatate arm compared to 4 percent in the Octreotide LAR 60mg arm (p<0.0148).

The most common grade 3-4 adverse reactions occurring with a greater frequency among patients in the NETTER-1 study receiving lutetium Lu 177 dotatate with octreotide compared to patients receiving high-dose octreotide include: lymphopenia (44%), increased gamma-glutamyl transferase (20%), vomiting (7%), nausea and elevated aspartate aminotransferase (5% each), and increased alanine aminotransferase, hyperglycemia, and hypokalemia (4% each).​


Monday, January 22, 2018

The FDA has granted Priority Review to the supplemental Biologics License Application (sBLA) for the use of daratumumab in combination with bortezomib, melphalan, and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT). 

The sBLA was submitted in November 2017. Priority Review is an FDA designation for drugs that treat a serious condition and may provide a significant improvement in safety or efficacy. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target date of May 21, 2018 to take a decision on daratumumab in this indication.

The sBLA submission was based on data from the phase III ALCYONE study (NCT02195479) of daratumumab in combination with bortezomib, melphalan, and prednisone in front-line multiple myeloma. This data was presented at the 2017 American Society of Hematology Annual Meeting and published in The New England Journal of Medicine in December 2017.

This randomized, open-label, multicenter study includes 706 newly diagnosed patients with multiple myeloma who are ineligible for ASCT. Patients were randomized to receive nine cycles of either VMP [bortezomib (a proteasome inhibitor), melphalan (an alkylating chemotherapeutic agent), and prednisone (a corticosteroid)] combined with daratumumab, or VMP alone.

In the daratumumab treatment arm, patients received 16 mg/kg of daratumumab once weekly for 6 weeks (cycle 1; 1 cycle = 42 days), followed by once every 3 weeks (cycles 2-9). Following the 9 cycles, patients in the daratumumab treatment arm continued to receive 16 mg/kg of daratumumab once every 4 weeks until disease progression. The primary endpoint of the study is progression free survival.