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FDA Actions & Updates

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

Thursday, March 17, 2016

The U.S. Food and Drug Administration has granted priority review designation to artezolizumab (MPDL3280A) for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who had disease progression during or following platinum-based chemotherapy in the metastatic setting, or whose disease worsened within 12 months of receiving platinum-based chemotherapy before surgery or after surgery.

The FDA's priority review designation shortens the time to complete a drug's review and aims to deliver a decision on marketing approval designation for drugs that may offer major advances in treatment or provide a treatment where no adequate therapy exists within six months under the Prescription Drug User Fee Act (PDUFA). The FDA action date for artezolizumab for this indication is September 12.

Previous FDA Actions for Artezolizumab
Artezolizumab has previously received breakthrough therapy designation for the treatment of patients with metastatic bladder cancer that expresses the protein PD-L1 (OT 6/25/14 issue). The drug has also previously received breakthrough therapy designation for the treatment of patients with PD-L1 positive non-small cell lung cancer whose disease has progressed during or after platinum-based chemotherapy (OT 2/25/15 issue).

Phase II and III Trials
This designation for artezolizumab is based on data from the open-label, multicenter, single-arm Phase II IMvigor 210 study that evaluated the safety and efficacy of artezolizumab in patients with locally advanced or metastatic urothelial cancer, regardless of PD-L1 expression. In an updated analysis based on 11.7 months of median follow up, treatment with artezolizumab shrank tumors in 15 percent of the patients show disease progressed after platinum-based chemotherapy. Atezolizumab shrank tumors in 26 percent of patients whose disease had medium and high levels of PD-L1 expression. And median duration of response was not reached at the time of analysis.

The most common grade 3 to 4 treatment-related adverse events included: fatigue, decreased appetite, pyrexia, anemia, enzymes in the blood, arthralgia, dyspnea, pneumonitis, colitis, hypertension, and hypotension. There were no treatment-related grade 5 adverse events.

A confirmatory Phase III study (IMvigor 211) is also ongoing in patients with bladder cancer that has progressed on at least one prior platinum-containing regimen. The trial is comparing treatment with artezolizumab with treatment with chemotherapy.

The drug is being developed by Genentech.

Thursday, March 17, 2016

The U.S. Food and Drug Administration has approved Imbruvica (ibrutinib) capsules for first-line treatment of patients with chronic lymphocytic leukemia (CLL). Imbruvica is targets and blocks Bruton's tyrosine kinase (BTK), inhibiting cancer cell survival and spread.

Imbruvica has previously been approved for: the treatment of Waldenstrom's macroglobulinemia (OT 2/25/15 issue); the treatment of patients with mantle cell lymphoma who have received one prior therapy (OT 12/10/13 issue) and patients with chronic lymphocytic leukemia who carry a deletion in chromosome 17 (OT 3/10/14 issue and 8/25/14 issue).

This expanded indication for Imbruvica for the treatment of patients with CLL is based on safety and efficacy data from the multicenter, open-label, Phase III RESONATE-2 trial of 269 patients with treatment-naïve CLL or small lymphocytic leukemia. The patients were randomized to receive Imbruvica (420mg orally) once daily until progression or unacceptable toxicity or chlorambucil (0.5-0.8mg/kg) on days one and 15 of each 28-day cycle for up to 12 cycles (with an allowance for intrapatient dose increases up to 0.8mg/kg based on tolerability).

Median progression-free survival for patients treated with Imbruvica was not reached compared with 18.9 months for patients treated with chlorambucil. Additionally, the overall response rate for patients treated with Imbruvica was 82.4 percent compared with 35.3 percent for patients treated with chlorambucil. And five patients treated with Imbruvica (3.7%) had a complete response compared with two patients treated with chlorambucil (1.5%).

The safety of Imbruvica for this study was consistent with previously reported studies. Warnings and precautions include hemorrhage, infections, cytopenias, atrial fibrillation, hypertension, second primary malignancies, tumor lysis syndrome, and embryo-fetal toxicity, according to a news release from the drug companies marketing the drug, Janssen and AbbVie. The most common adverse events were diarrhea, musculoskeletal pain, cough, and rash. The most common Grade 3/4 adverse event was pneumonia.

Monday, March 7, 2016

The U.S. Food and Drug Administration has approved Afinitor (everolimus) tablets for the treatment of adult patients with progressive, well-differentiated, nonfunctional neuroendocrine tumors (NETs) of gastrointestinal (GI) or lung origin that are resectable, locally advanced, or metastatic.

Approval of Afinitor for these indications was based on safety and efficacy data from the RADIANT-4, Phase III prospective, double-blind, randomized, parallel group, placebo-controlled, multicenter study of 302 patients with unresectable, progressive, well-differentiated, nonfunctional, locally advanced or metastatic NET of GI (excluding pancreatic) or lung origin. Patients were randomized two to one to receive daily Afinitor (10mg) or daily oral placebo, with all patients receiving best supportive care. The data showed patients receiving Afinitor had a median progression-free survival of 11 months compared with 3.9 months for patients receiving the placebo.

The most common adverse reactions for patients receiving Afinitor were stomatitis, diarrhea, peripheral edema, fatigue and infections; and the most common serious adverse reactions were stomatitis, diarrhea, fatigue, infections and hyperglycemia.

Afinitor is marketed by Novartis.

Monday, March 7, 2016

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Robert M. Califf, MD

Robert M. Califf, MD, has been confirmed as Commissioner of the U.S. Food and Drug Administration. Prior to this appointment, Califf served as FDA's Deputy Commissioner for Medical Products and Tobacco, for which he provided executive leadership to the Center for Drug Evaluation and Research, the Center for Biologics Evaluation and Research, the Center for Devices and Radiological Health, and the Center for Tobacco Products. He also oversaw the Office of Special Medical Programs.

"Dr. Califf has demonstrated a long and deep commitment to advancing the public health throughout his distinguished career as a physician, researcher, and leader in the fields of science and medicine," Stephen Ostroff, MD, the FDA's Chief Scientist and former Acting Commissioner, said in a statement.  "He understands well the critical role that the FDA plays in responding to the changes in our society while protecting and promoting the health of the public, across the many areas we regulate—and I am confident that our public health and scientific contributions will further grow under his exceptional leadership."

Prior to joining the FDA, Califf served as Professor of Medicine and Vice Chancellor for Clinical and Translational Research at Duke University. He was also Director of the Duke Translational Medicine Institute and founding Director of the Duke Clinical Research Institute. Califf has also served on several Institute of Medicine committees, including the IOM Committee on Identifying and Preventing Medication Errors, as well as the IOM Health Sciences Policy Board. He has also served as a member of the FDA Cardiorenal Advisory Panel and FDA Science Board's Subcommittee on Science and Technology.

In a statement, Richard L. Schilsky, MD, FACP, Chief Medical Officer of the American Society of Clinical Oncology, noted: "Dr. Califf brings extraordinary expertise and vision to this position and we are confident that his appointment will positively impact cancer care.

"Dr. Califf's considerable expertise and long experience in clinical and translational medicine makes him well-suited to lead the FDA's efforts to assure the safety and effectiveness of treatments and medical devices to ensure that the right treatment is delivered to the right person at the right time."

José Baselga, MD, PhD, President of the American Association for Cancer Research and Physician-in-Chief and Chief Medical Officer at Memorial Sloan Kettering Cancer Center, noted in a statement: "While the scientific opportunities that exist today to develop more effective cancer treatments have never been greater, we also recognize that the science is increasingly complex, especially when factoring in the rapidly expanding effectiveness of molecularly targeted therapies and combination therapies. … Therefore, this extraordinary time of promise will require an experienced and visionary leader at the FDA to ensure that the necessary regulatory framework is in place to approve innovative therapies that are both safe and effective, and we believe Dr. Califf is the right person for this extremely important position."

Friday, February 26, 2016

The U.S. Food and Drug Administration has expanded the approved indication for Ibrance (palbociclib) now for the treatment of patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with fulvestrant in women whose disease has progressed following endocrine therapy. Ibrance is an oral, cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor.

Ibrance had previously received the FDA's breakthrough therapy and priority review designations for this indication (OT 1/10/16 issue).  

Ibrance has also previously been approved for use in combination with letrozole as a treatment for postmenopausal women with ER-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease (OT 3/10/15 issue). This indication is approved under accelerated approval based on progression-free survival, and continued approval for this indication may be contingent upon verification and description of clinical benefit in the ongoing confirmatory trial, PALOMA-2.

This new expanded approval for Ibrance is based on data from the Phase III PALOMA-3 trial of 521 women with HR-positive, HER2-negative advanced breast cancer whose disease had progressed on prior endocrine therapy, regardless of menopausal status, who received either Ibrance plus fulvestrant or placebo plus fulvestrant (OT 8/10/15 issue). Women receiving the Ibrance-fulvestrant combination had a median progression-free survival of 9.5 months compared to 4.6 months for patients who received placebo plus fulvestrant. Duration of response was 9.3 months for the patients receiving the Ibrance combination, compared with 7.6 months for patients receiving the placebo combination.

The most common adverse events for patients receiving Ibrance plus fulvestrant were neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, headache, diarrhea, thrombocytopenia, constipation, vomiting, alopecia, rash, decreased appetite, and pyrexia. The most frequently reported serious adverse events for patients receiving Ibrance plus fulvestrant were infections, pyrexia, neutropenia, and pulmonary embolism.

Ibrance is marketed by Pfizer Oncology.

About the Author

Sarah DiGiulio