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

Friday, February 24, 2017

The FDA has expanded the existing indication for lenalidomide 10 mg capsules to include use for patients with multiple myeloma as maintenance therapy following autologous hematopoietic stem cell transplant (auto-HSCT). The expanded indication makes lenalidomide the first and only treatment to receive FDA approval for maintenance use following auto-HSCT.

"Autologous stem cell transplant after induction therapy is part of the continuum of care for transplant-eligible multiple myeloma patients. However, most patients will still see their disease recur or progress after this treatment," said Philip McCarthy, MD, Director, Blood and Marrow Transplant Center, Department of Medicine at Roswell Park Cancer Institute. "Lenalidomide maintenance therapy, which has been shown to increase progression-free survival following autologous stem cell transplant in clinical trials can be considered a standard of care for these patients."

The approval was based on two large studies including more than 1,000 patients comparing lenalidomide maintenance therapy given until disease progression or unacceptable toxicity after auto-HSCT versus no maintenance. In both studies, the primary efficacy endpoint was progression-free survival (PFS) defined from randomization to the date of progression or death, whichever occurred first. In the most current PFS analysis, the CALGB 100104 study demonstrated a median PFS of 5.7 years (95% CI: 4.4-not estimable) versus 1.9 years (95% CI: 1.6-2.5) for no maintenance, a difference of 3.8 years (HR 0.38 [95% CI: 0.28-0.50]). The second study, IFM 2005-02, also showed a benefit with a median PFS of 3.9 years (95% CI: 3.3-4.7) versus 2 years (95% CI: 1.8-2.3) for no maintenance, a difference of 1.9 years (HR 0.53 [95% CI: 0.44-0.64]).

Individual studies were not powered for an overall survival endpoint. A descriptive analysis showed the median overall survival in CALGB 100104 was 9.3 years (95% CI: 8.5-not estimable) for patients who received lenalidomide versus 7 years (95% CI: 5.9-8.6) for no maintenance (HR 0.59 [95% CI: 0.44-0.78]). In the CALGB 100104 study, median overall survival was 8.8 years (95% CI: 7.4-not estimable) for patients who received lenalidomide versus 7.3 years (95% CI: 6.7-9.0) for no maintenance (HR 0.90 [95% CI: 0.72-1.13]).

Lenalidomide in combination with dexamethasone was previously approved in June 2006 for use in patients with multiple myeloma who have received at least one prior therapy, and the indication expanded in February 2015 to include patients newly diagnosed with multiple myeloma.


Friday, February 3, 2017

​​The FDA has granted accelerated approval to nivolumab for treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with a platinum-containing chemotherapy.

Approval was based on a single-arm study treating 270 patients with locally advanced or metastatic urothelial carcinoma who progressed during or following platinum-containing chemotherapy, or progressed within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Patients received nivolumab, 3 mg/kg every 2 weeks, until disease progression or unacceptable toxicity. Objective response rate, confirmed by an independent radiographic review committee using Response Evaluation Criteria in Solid Tumors 1.1, was 19.6 percent (53/270; 95% CI: 15.1, 24.9). Seven patients had complete responses and 46 had partial responses. Estimated median response duration was 10.3 months with responses ongoing at data cutoff.

The most common adverse reactions (reported in at least 20% of patients) were fatigue, musculoskeletal pain, nausea, and decreased appetite. Fourteen patients died from causes other than disease progression, including four patients who died from pneumonitis or cardiovascular failure attributed to nivolumab. Adverse reactions led to dose discontinuation in 17 percent of patients.

The recommended dose and schedule for nivolumab for the above indication is 240 mg intravenously every 2 weeks.


Tuesday, January 24, 2017

The FDA has approved ibrutinib for the treatment of patients with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy. 

Accelerated approval was granted for this indication based on overall response rate (ORR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

"Patients with relapsed/refractory marginal zone lymphoma are in critical need of treatment options to manage living with this rare, serious blood cancer," said Ariela Noy, MD, Hematologic Oncologist at Memorial Sloan Kettering Cancer Center in New York and lead investigator of the study. "This approval of ibrutinib represents a welcome new oral option for the MZL community and is the first approved therapy for these patients." 

The approval is based on results from the multi-center, open-label single arm, phase II PCYC-1121 trial assessing the safety and efficacy of ibrutinib in 63 patients with MZL who received at least one prior therapy, including all three subtypes: mucosa-associated lymphoid tissue (MALT; n=32), nodal MZL (NMZL; n=17), and splenic MZL (SMZL; n=14).

The responses were assessed by an Independent Review Committee (IRC) using criteria adopted from the International Working Group criteria for malignant lymphoma and demonstrated a 46 percent ORR (95% CI: 33.4-59.1), with 3.2 percent of patients achieving complete responses and 42.9 percent achieving partial responses.  

Efficacy was observed across all three MZL subtypes (ORR of 46.9%, 41.2%, and 50.0% for MALT, nodal, and splenic subtypes, respectively). The median duration of response was not reached (range, 16.7-NR), with median follow-up of 19.4 months. The median time to initial response was 4.5 months (range, 2.3-16.4). The data were presented at the 58th Annual American Society of Hematology (ASH) Meeting in December 2016 (Abstract 1213).

Warnings and precautions for ibrutinib include hemorrhage, infections, cytopenias, atrial fibrillation, hypertension, second primary malignancies, tumor lysis syndrome, and embryo-fetal toxicity. The most common (>20%) adverse events (AEs) of all grades included thrombocytopenia (49%), fatigue (44%), anemia (43%), diarrhea (43%), bruising (41%), musculoskeletal pain (40%), hemorrhage (30%), rash (29%), nausea (25%), peripheral edema and arthralgia (24% each), neutropenia (22%), cough (22%), and dyspnea and upper respiratory tract infection (21% each). The most common (>10%) grade 3 or 4 AEs were decreases in hemoglobin and neutrophils (13% each) and pneumonia (10%).


Wednesday, January 11, 2017

The FDA has accepted the supplemental Biologics License Application (sBLA) and granted Priority Review for atezolizumab (Tecentriq) for the treatment of people with locally advanced or metastatic urothelial carcinoma (mUC) who are ineligible for cisplatin chemotherapy, and are either previously untreated or have disease progression at least 12 months after receiving neoadjuvant or adjuvant chemotherapy.

Atezolizumab is a monoclonal antibody designed to bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, atezolizumab may enable the activation of T cells; it may also affect normal cells.

This sBLA submission for atezolizumab is based on results from the phase II IMvigor210 study, and the FDA will make a decision on approval by April 30, 2017. A Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the safety and effectiveness of the treatment, prevention, or diagnosis of a serious disease.

Atezolizumab is currently approved by the FDA to treat people with locally advanced or mUC who have disease progression during or following platinum-based chemotherapy or whose disease has worsened within 12 months of neoadjuvant or adjuvant platinum-based chemotherapy. Atezolizumab is approved under accelerated approval for this indication based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Atezolizumab is also approved for the treatment of people with metastatic non-small cell lung cancer who have disease progression during or following platinum-containing chemotherapy, and have progressed on an appropriate FDA-approved targeted therapy if their tumor has EGFR or ALK gene abnormalities. 


Monday, January 9, 2017

Priority review status has been granted by the FDA for the supplemental New Drug Application (sNDA) for regorafenib (Stivarga) tablets for the second-line systemic treatment of patients with hepatocellular carcinoma (HCC) in the U.S.

HCC is the most common form of liver cancer, a disease that affects nearly 40,000 patients in the United States and is the second deadliest form of cancer worldwide.

The FDA grants priority review to medicines that, if approved, would provide significant improvements in the safety or effectiveness of the treatment for serious conditions. Under the Prescription Drug User Fee Act (PDUFA), the FDA aims to complete its review within 6 months (compared to 10 months under standard review).

The sNDA is based on data from the international, multicenter, placebo-controlled phase III RESORCE trial which investigated regorafenib in patients with HCC whose disease had progressed during treatment with Nexavar.

Regorafenib is currently approved for the treatment of patients with metastatic colorectal cancer (mCRC) who have previously been treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild type, an anti-EGFR therapy, as well as the treatment of patients with locally advanced, unresectable, or metastatic gastrointestinal stromal tumor (GIST), who were previously treated with imatinib mesylate and sutinib maleate.