Skip to main content

Temodar Receives FDA Approval for New and Updated Indications and Doses Through the Project Renewal Program

Web Exclusives - FDA Approvals

On September 14, 2023, the FDA approved new and updated indications for temozolomide (Temodar; Merck) capsules and injection, an alkylating drug, including for the adjuvant treatment of adults with newly diagnosed anaplastic astrocytoma, and for the treatment of adults with refractory anaplastic astrocytoma. The previously approved indication for the treatment of adults with newly diagnosed glioblastoma, concomitant with radiotherapy, then as maintenance treatment, remains unchanged.

This updated FDA approval includes additional prescribing revisions for temozolomide. Temozolomide has revised dosing regimens and is now administered orally or intravenously for patients newly diagnosed with glioblastoma and for those newly diagnosed with anaplastic astrocytoma or those with refractory anaplastic astrocytoma. For complete dosing details, refer to temozolomide’s complete prescribing information. The Warnings and Precautions section of the prescribing information includes a new warning for temozolomide capsules regarding the risks from exposure to opened capsules, emphasizing that the capsules should not be opened, chewed, or dissolved, but should be swallowed whole with a glass of water. The Patient Counseling Information section and the Patient Information document for temozolomide were also updated. For complete details on the revisions, please refer to temozolomide’s prescribing information.

The efficacy of temozolomide for the adjuvant treatment of patients with newly diagnosed anaplastic astrocytoma was based on published studies involving temozolomide, specifically the randomized, open-label, multicenter CATNON clinical study (NCT00626990), which investigated the use of temozolomide in patients with anaplastic astrocytoma as adjuvant therapy to radiation therapy versus radiation therapy alone, with a major efficacy outcome measure of overall survival (OS).

The efficacy of temozolomide for the treatment of refractory anaplastic astrocytoma was evaluated in the single-arm, multicenter, clinical MK-7365-006 study. All patients had anaplastic astrocytoma at first relapse and a baseline Karnofsky Performance Scale (KPS) score of ≥70. The patients previously received radiation therapy and could have also received a nitrosourea compound, with or without another chemotherapy. In all, 54 patients had disease progression during previous therapy with a nitrosourea compound and procarbazine, and their disease was refractory to chemotherapy (ie, the population with refractory anaplastic astrocytoma). Temozolomide capsules were received on days 1 to 5 of each 28-day cycle, at a starting dose of 150 mg/m2 daily. If the absolute neutrophil count was ≥1.5 × 109/L, and the platelet count was ≥100 × 109/L at the nadir and on day 1 of the next cycle, the temozolomide dose was increased to 200 mg/m2 daily.

The main efficacy measure was progression-free survival (PFS) at 6 months; the secondary outcomes were OS and overall response rate (ORR). The patients with refractory anaplastic astrocytoma (n=54) had a median age of 42 years (range, 19-76 years), 65% were male, and 72% had a KPS score of >80. At diagnosis, 63% of the patients had surgery (excluding biopsy). Of those patients undergoing surgical resection, 73% had subtotal resection and 27% had gross total resection; 18% of the patients had surgery at the first disease relapse. The median time from initial diagnosis to first relapse was 13.8 months (range, 4.2 months-6.3 years).

In the 54 patients with refractory anaplastic astrocytoma, the ORR (complete response [CR] plus partial response) was 22% (n=12) and the CR rate was 9% (n=5). The median duration of all responses was 50 weeks (range, 16-114 weeks); the median duration of CR was 64 weeks (range, 52-114 weeks). In this population, the 6-month PFS was 45% (95% confidence interval [CI], 31%-58%) and the 12-month PFS was 29% (95% CI, 16%-42%), with a median PFS of 4.4 months. The 6-month OS was 74% (95% CI, 62%-86%) and the 12-month OS was 65% (95% CI, 52%-78%), with a median OS of 15.9 months.

The FDA approved these new and updated indications and additional clinical information under its Project Renewal program, a collaborative initiative of the Oncology Center of Excellence that is aimed at updating the prescribing information for older oncology drugs, to ensure that a drug’s prescribing information is based on up-to-date scientific information that is clinically meaningful. According to the FDA, Project Renewal is limited to older oncology drugs with decades of use, multiple supportive clinical studies, and substantial postmarketing experience. Temozolomide was first approved by the FDA in 1999 for patients newly diagnosed with glioblastoma and is the second drug to receive an update to its prescribing information under this pilot program (the first drug was capecitabine [Xeloda]).

The most common (≥20%) adverse reactions associated with temozolomide treatment include alopecia, fatigue, nausea, vomiting, headache, constipation, anorexia, and convulsions; the most common (≥10%) grade 3 or 4 hematologic laboratory abnormalities in patients with anaplastic astrocytoma include decreased lymphocytes, decreased platelets, decreased neutrophils, and decreased leukocytes.

Temozolomide is contraindicated in patients with serious hypersensitivity to temozolomide, to any of the other ingredients in Temodar, or to dacarbazine.

Related Items
Fruzaqla FDA Approved for Refractory Metastatic Colorectal Cancer
Web Exclusives published on December 6, 2023 in FDA Approvals
Rozlytrek Now Approved for Pediatric Patients Older Than 1 Month With Solid Tumors and NTRK Gene Fusion and in New Oral Pellet Form
Web Exclusives published on December 6, 2023 in FDA Approvals
FDA Authorizes Updated COVID-19 Vaccine Formulations for Better Protection Against Current Variants
Web Exclusives published on November 16, 2023 in FDA Approvals
Bosulif Now FDA Approved for Pediatric Patients With Chronic Myelogenous Leukemia
Web Exclusives published on November 1, 2023 in FDA Approvals
FDA Approved Abrysvo, First RSV Vaccine for Immunizing Pregnant Women, as Prophylaxis Against RSV Infection in Infants
Web Exclusives published on October 30, 2023 in FDA Approvals
Last modified: October 31, 2023