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I. New Drugs

TOP - February 2019, Vol 12, No 1 - FDA Approvals

Talzenna Approved for HER2-Negative, Locally Advanced Breast Cancer with Germline BRCA Mutations

On October 16, 2018, the FDA approved talazoparib (Talzenna; Pfizer), a poly (ADP-ribose) polymerase (PARP) inhibitor, for the treatment of patients with HER2-­negative, locally advanced or metastatic breast cancer and deleterious or suspected deleterious germline BRCA mutation, as identified by an FDA-approved test.

On the same day, the FDA approved the companion diagnostic BRACAnalysis CDx test, to identify patients with breast cancer who are candidates for talazoparib therapy, namely, those with deleterious or suspected deleterious germline BRCA mutation.

This approval was based on results of a phase 3, international, open-label clinical trial of 431 patients with germline BRCA-positive, HER2-­negative, locally advanced or metastatic breast cancer. Enrolled patients had received ≤3 cytotoxic chemotherapy regimens and were randomized to talazoparib therapy or to physician’s choice of chemotherapy.

The primary end point was progression-free survival (PFS). At a median follow-up of 11.2 months, the median PFS was 8.6 months in the talazoparib arm versus 5.6 months in the chemotherapy arm (hazard ratio, 0.54; 95% confidence interval, 0.41-0.71; P <.0001).

The most common (≥20%) adverse events of any grade with talazoparib were fatigue, anemia, nausea, neutro­penia, headache, thrombocytopenia, vomiting, alopecia, diarrhea, and reduced appetite.

Udenyca, Second Biosimilar to Neulasta, FDA-Approved to Reduce Risk for Infection in Patients with Nonmyeloid Malignancies

On November 2, 2018, the FDA approved pegfilgrastim-cbqv (Udenyca; Coherus BioSciences), as the second biosimilar to pegfilgrastim (Neulasta), to reduce the risk for infection in patients with nonmyeloid malignancies who receive myelosuppressive chemotherapy, which may result in febrile neutropenia.

The approval of pegfilgrastim-­cbqv was based on a variety of studies confirming that it is a biosimilar to the reference drug Neulasta.

The most common (5%) adverse events with pegfilgrastim-­cbqv are bone pain and pain in extremities. Serious adverse events include aortitis, splenic rupture, acute respiratory distress syndrome, serious allergic reactions, glomerulonephritis, leukocytosis, and capillary leak syndrome.

Treatment with pegfilgrastim-­cbqv may also cause fatal sickle-cell crisis in patients with sickle-cell disorders, stimulate tumor growth on malignant cells, and cause transient positive nuclear imaging changes because of increased hematopoietic activity of the bone marrow.

Daurismo New Treatment Approved for Older Adults with Acute Myeloid Leukemia

On November 21, 2018, the FDA approved glasdegib (Daurismo; Pfizer), an oral Hedgehog inhibitor, in combination with low-dose cytarabine (LDAC), for patients with newly diagnosed acute myeloid leukemia (AML) who are aged ≥75 years or who have comorbidities that preclude use of intensive induction chemotherapy. The FDA approved glasdegib using its priority review and granted it an orphan drug designation.

This approval was based on a multicenter, open-label, randomized study of 115 patients with newly diagnosed AML who were aged ≥75 years, had severe cardiac disease, had a baseline Eastern Cooperative Oncology Group performance status 2, or had baseline serum creatinine >1.3 mg/dL. Patients were randomized in a 2:1 ratio to glasdegib 100 mg daily, with LDAC 20 mg subcutaneously twice daily on days 1 to 10 of a 28-day cycle or to LDAC alone in 28-day cycles until disease progression or unacceptable toxicity.

The primary end point was overall survival (OS). At a median follow-up of 20 months, the median OS was 8.3 months (95% confidence interval [CI], 4.4-12.2) with glasdegib plus LDAC versus 4.3 months (95% CI, 1.9-5.7) with LDAC alone (hazard ratio, 0.46; 95% CI, 0.30-0.71; P = .0002).

The most common (≥20%) side effects with glasdegib were anemia, fatigue, hemorrhage, febrile neutropenia, musculoskeletal pain, nausea, edema, thrombocytopenia, dyspnea, decreased appetite, dysgeusia, mucositis, constipation, and rash. Glasdegib has not been studied in patients with severe renal impairment or with moderate-to-severe hepatic impairment.

Xospata First Monotherapy Approved for Relapsed or Refractory Acute Myeloid Leukemia with FLT3 Mutation

On November 28, 2018, the FDA approved gilteritinib (Xospata; Astellas Pharma) for adult patients with relapsed or refractory acute myeloid leukemia (AML) and an FLT3 mutation, as identified by an FDA-­approved test. The FDA approved gilteritinib using its fast track and priority review and granted it an orphan drug designation.

On the same day, the FDA also approved an expanded indication for the companion diagnostic LeukoStrat CDx FLT3 Mutation Assay, to expand its use for gilteritinib. This companion diagnostic is used to detect FLT3 mutations in patients with AML.

The approval of gilteritinib was based on an interim analysis of the ADMIRAL clinical trial of 138 adults with relapsed or refractory AML and an FLT3 ITD, D835, or I836 mutation, as detected by the LeukoStrat CDx FLT3 Mutation Assay. Oral gilteritinib was used daily until unacceptable toxicity or lack of clinical benefit. At a median follow-up of 4.6 months, 29 (21%) patients achieved a complete remission (CR) or CR with partial hematologic recovery (95% confidence interval, 14.5-28.8). Of the 106 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 33 (31.1%) became independent of RBC and platelet transfusions during any 56-day postbaseline period. For the 32 patients who were independent of RBC and platelet transfusions at baseline, 17 (53.1%) remained transfusion-independent during any 56-day postbaseline period.

The most common (≥20%) adverse events were myalgia/arthralgia, transaminase increase, fatigue/malaise, fever, noninfectious diarrhea, dyspnea, edema, rash, pneumonia, nausea, stomatitis, cough, headache, hypotension, dizziness, and vomiting.

Truxima First Biosimilar to Rituxan FDA-Approved for Non-Hodgkin Lymphoma

On November 28, 2018, the FDA approved rituximab-abbs (Truxima; Celltrion) as the first biosimilar to ri­tuximab (Rituxan; Genentech) for patients with CD20-positive, B-cell non-Hodg­kin lymphoma (NHL), for use as a single agent or in combination with chemotherapy.

Truxima is indicated for the treatment of adults with relapsed or refractory, low-grade or follicular, CD20-positive B-cell NHL as a single agent; untreated follicular, CD20-positive B-cell NHL, in combination with first-line chemotherapy, and, in patients achieving a complete or partial response to rituximab therapy plus chemotherapy, as single-agent maintenance therapy; and for patients with nonprogressing (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent after first-line cyclophosphamide, vincristine, and prednisone chemotherapy.

The approval was based on extensive data demonstrating that Truxima is biosimilar to Rituxan.

The most common side effects of Truxima are infusion reactions, fever, lymphopenia, chills, infection, and asthenia.

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Last modified: June 4, 2019