TazverikTM Now Approved for Both Epithelioid Sarcoma and Follicular Lymphoma
by Dr. David Schoenbaechler, PharmD, BCOP, CSP
Dr. Joseph Barone, PharmD, BCOP
Tazverik (tazemetostat) is a methyltransferase inhibitor indicated for the treatment of adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection, adult patients with relapsed or refractory follicular lymphoma whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least two prior systemic therapies, and adult patients with relapsed or refractory follicular lymphoma who have no satisfactory alternative treatment options.
Tazverik works by blocking the activity of the EZH2 methyltransferase enzyme, thereby reducing aberrant enzyme activity and resulting in reduced oncogenesis. The FDA based its approval for epithelioid sarcoma on the Phase II EZH-202 (NCT02601950) clinical trial which involved 62 patients with locally-advanced or metastatic epithelioid sarcoma. This clinical trial demonstrated that Tazverik administration resulted in a 15% overall response rate (ORR) in this patient population. Additionally, in patients who responded to Tazverik treatment, 67% of patients responded to therapy for at least six months.
Tazverik’s approval for relapsed/refractory follicular lymphoma was based on the Phase II E7438-G000-101 (NCT01897571) clinical trial which involved95 patients with relapsed/refractory follicular lymphoma who had received at least two prior systemic therapies. In patients with EZH2-mutant follicular lymphoma, Tazverik administration resulted in an ORR of 69% with a median duration of response of 10.9 months. In patients with EZH2 wild-type follicular lymphoma, Tazverik administration resulted in an ORR of 34% with a median duration of response of 13.0 months.
The recommended dosage regardless of the indication for use, of Tazverik is 800 mg taken orally twice daily with or without food until disease progression or unacceptable toxicity. Patients should be instructed to swallow the tablets whole. In the event that a dose is missed or vomiting occurs after administration, patients should not take an additional dose but rather continue with the next scheduled dose.
Tazverik’s prescribing information contains warnings and precautions for secondary malignancies and embryo-fetal toxicity. Tazverik increases the risk of developing secondary malignancies, including T-cell lymphoblastic lymphoma, myelodysplastic syndrome, and acute myeloid leukemia. These hematological malignancies occurred in 0.7% of patients receiving Tazverik as part of a clinical trial. Based on findings from animal studies, Tazverik can cause fetal harm when administered to pregnant women. Females of reproductive potential should use effective contraception during treatment with Tazverik and for six months after the last dose. Males with female partners of reproductive potential should use effective contraception during treatment with Tazverik and for three months after the last dose.
The most common (≥20%) adverse reactions in Tazverik patients with epithelioid sarcoma are pain, fatigue, nausea, decreased appetite, vomiting, and constipation. The most common (≥20%) adverse reactions in Tazverik patients with follicular lymphoma are fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain.
Coadministration of Tazverik with strong and moderate cytochrome P450 (CYP) 3A inhibitors (i.e. azoles, diltiazem, erythromycin, grapefruit, etc.) should be avoided. The dose of Tazverik should be reduced if coadministration of moderate CYP3A inhibitors cannot be avoided. Coadministration of Tazverik with strong and moderate CYP3A inducers (e.g., phenytoin, phenobarbital, rifampicin, St. John’s Wort) should be avoided.
Tazverik is available as 200 mg tablets in bottles containing 240 tablets. The tablets should not be stored above 30°C (86°F).
References:
- Tazverik [package insert]. Cambridge, MA: Epizyme, Inc., 2020.
- Cancer.org. FDA Approves Tazverik (Tazemetostat) for Epithelioid Sarcoma. January 24, 2020. Available at: https://www.cancer.org/latest-news/fda-approves-tazverik-tazemetostat-for-epithelioid-sarcoma.html.
- 3Biospace.com. Epizyme’s Tazverik Picks Up Its Second FDA Approval of 2020. June 19, 2020. Available at: https://www.biospace.com/article/epizyme-s-tazverik-picks-up-second-fda-approval-of-2020/