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Treatment for Chronic Graft-Versus-Host Disease Approved

The FDA has expanded the approval of ibrutinib for the treatment of adult patients with chronic graft-versus-host disease (cGVHD) after failure of one or more treatments. This is the first FDA-approved therapy for the treatment of cGVHD.

FDA; lung cancer; AM... - Click to enlarge in new windowFDA; lung cancer; AML; colorectal cancer. FDA; lung cancer; AML; colorectal cancer

"Patients with cGVHD who do not respond to other forms of therapy-typically corticosteroids to suppress their immune system-now have a treatment option specifically indicated to treat their condition," 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. "This approval highlights how a known treatment for cancer is finding a new use in treating a serious and life-threatening condition that may occur in patients with blood cancer who receive a stem cell transplant."


The efficacy and safety of ibrutinib for the treatment of cGVHD were studied in a single-arm trial of 42 patients with cGVHD whose symptoms persisted despite standard treatment with corticosteroids. Most patients' symptoms included mouth ulcers and skin rashes, and more than 50 percent of patients had two or more organs affected by cGVHD. In the trial, 67 percent of patients experienced improvements in their cGVHD symptoms. In 48 percent of patients in the trial, the improvement of symptoms lasted for up to 5 months or longer.


Common side effects of ibrutinib in patients with cGVHD include fatigue, bruising, diarrhea, thrombocytopenia, muscle spasms, stomatitis, nausea, hemorrhage, anemia, and pneumonia.


Ibrutinib, a kinase inhibitor, was previously approved for certain indications in treating chronic lymphocytic leukemia, Waldenstrom's macroglobulinemia, and marginal zone lymphoma, as well as under accelerated approval status for mantle cell lymphoma.


The FDA granted this application Priority Review and Breakthrough Therapy designations. Ibrutinib also received Orphan Drug designation for this indication.


Alectinib Granted Priority Review for ALK-Positive Lung Cancer

The FDA has accepted the supplemental New Drug Application (sNDA) and granted Priority Review for alectinib as a first-line treatment for people with anaplastic lymphoma kinase (ALK)-positive, locally advanced, or metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test.


This sNDA submission for alectinib is based on results from the phase III ALEX and phase III J-ALEX studies. A Priority Review designation is granted to proposed medicines that, if approved, the FDA has determined to have the potential to provide a significant improvement in the safety or effectiveness of the treatment, prevention, or diagnosis of a serious disease.


Results from the phase III ALEX study and updated results from the phase III J-ALEX study were recently presented at the 2017 ASCO Annual Meeting.


ALEX (NCT02075840/B028984) is a randomized, multicenter, open-label, phase III study evaluating the efficacy and safety of alectinib versus crizotinib in treatment-naive people with ALK-positive NSCLC whose tumors were characterized as ALK-positive by the VENTANA ALK (D5F3) CDx Assay. People were randomized (1:1) to receive either alectinib or crizotinib. The multicenter study was conducted in 303 people across 161 sites in 31 countries.


The J-ALEX study is an open-label, randomized, phase III study that compared the efficacy and safety of alectinib with crizotinib in Japanese people. J-ALEX enrolled 207 people with ALK-positive, advanced, or recurrent NSCLC who had not been treated with an ALK inhibitor. People were randomized 1:1 to the alectinib group or the crizotinib group.


Alectinib received Breakthrough Therapy Designation from the FDA in September 2016 for the treatment of adults with advanced ALK-positive NSCLC who have not received prior treatment with an ALK inhibitor. This designation is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases and help ensure people have access to them through FDA approval as soon as possible. Breakthrough Therapy Designation was granted on the basis of the phase III J-ALEX trial.


Therapy for Certain Types of Poor-Prognosis AML Approved

The FDA has approved daunorubicin and cytarabine combination therapy for the treatment of adults with two types of acute myeloid leukemia (AML): newly-diagnosed therapy-related AML or AML with myelodysplasia-related changes (MRC).


"This is the first approved treatment specifically for patients with certain types of high-risk AML," 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. "[The treatment] combines two commonly used chemotherapies into a single formulation that may help some patients live longer than if they were to receive the two therapies separately."


The safety and efficacy of the combination therapy were studied in 309 patients with newly-diagnosed t-AML or AML-MRC who were randomized to receive the drug or separately administered treatments of cytarabine and daunorubicin. The trial measured overall survival (OS). Patients who received the combination lived longer than patients who received separate treatments of cytarabine and daunorubicin (median OS 9.56 months vs. 5.95 months).


Common side effects include hemorrhage, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders, and vomiting.


Nivolumab Approved for Use in Metastatic Colorectal Cancer

The FDA has approved nivolumab injection for IV use for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC) that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.


Approval for this indication has been granted under Accelerated Approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. The recommended dose is 240 mg administered as an IV infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity.


In the CheckMate 142 trial, among patients (53/74) who received prior treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, 28 percent (95% CI: 17-42; 15/53) responded to treatment with nivolumab. The percentage of patients with a complete response was 1.9 percent (1/53) and the percentage of patients with a partial response was 26 percent (14/53). Among these responders, the median duration of response was not reached (range: 2.8+-22.1+ months). Among all enrolled patients, 32 percent (95% CI: 22-44; 24/74) responded to treatment with nivolumab, 2.7 percent (2/74) experienced a complete response, and 30 percent (22/74) experienced a partial response.


Nivolumab is associated with the following warnings and precautions, including immune-mediated: pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin adverse reactions, encephalitis, and other adverse reactions; infusion reactions; and embryo-fetal toxicity.


"Patients with metastatic colorectal cancer who have dMMR or MSI-H tumors are less likely to respond to conventional chemotherapy," said Heinz-Josef Lenz, MD, FACP, J. Terrence Lanni Chair in Gastrointestinal Cancer Research at the University of Southern California, Los Angeles. "While the challenges of treating these patients have been significant, tumors characterized by these biomarkers are immunogenic. Therefore, advances in immunotherapy research are encouraging in presenting new treatment options for appropriate patients with MSI-H metastatic colorectal cancer."