TRODELVY

What it is

TRODELVY is sacituzumab govitecan powder for injection, with each single-dose vial delivering 180 mg sacituzumab govitecan. Sacituzumab govitecan is a Trop-2-directed antibody-drug conjugate. Sacituzumab is a humanised antibody that recognises Trop-2, and the small molecule SN-38, a topoisomerase I inhibitor, is covalently attached to the antibody by a linker. The product binds to Trop-2-expressing cancer cells and is internalised with the subsequent release of SN-38 via hydrolysis of the linker, which interacts with topoisomerase I and prevents re-ligation of topoisomerase I-induced single strand breaks, resulting in DNA damage that leads to apoptosis and cell death. This medicinal product is subject to additional monitoring in Australia.

Approved indications

— Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) in adult patients who have received at least two prior systemic therapies, including at least one prior therapy for locally advanced or metastatic disease. — Unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer in adult patients who have received endocrine-based therapy (including a CDK4/6 inhibitor) and at least two additional systemic therapies in the locally advanced or metastatic setting.

Dosing overview

The recommended dose of TRODELVY is 10 mg/kg administered as an intravenous (IV) infusion once weekly on Days 1 and 8 of 21-day treatment cycles. Treatment continues until disease progression or unacceptable toxicity. The first infusion is administered over 3 hours, and subsequent infusions are administered over 1 to 2 hours if prior infusions were tolerated.

Key safety warnings

TRODELVY can cause severe or life-threatening neutropenia, and fatal infections in the setting of neutropenia have been observed in clinical trials, primarily in the first two cycles of treatment. Primary prophylaxis with G-CSF is recommended starting in the first cycle of treatment in patients at increased risk of febrile neutropenia, including older patients (in particular aged 65 years and older), patients with previous neutropenia, poor performance status, organ dysfunction, or multiple comorbid conditions. Neutropenia occurred in 68% of patients treated with TRODELVY, including Grade 3-4 neutropenia in 51% of patients, and febrile neutropenia occurred in 6% of patients. TRODELVY can cause severe diarrhoea, and treatment must be withheld for Grade 3-4 diarrhoea at the time of scheduled treatment administration and resumed when resolved to Grade 1 or less. Diarrhoea occurred in 63% of all patients treated with TRODELVY, with Grade 3 diarrhoea occurring in 10% of all patients. Diarrhoea in some cases has led to dehydration and subsequent acute kidney injury. TRODELVY can cause severe and life-threatening hypersensitivity, with severe signs and symptoms including cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. Hypersensitivity reactions within 24 hours of dosing occurred in 33% of patients treated with TRODELVY, and Grade 3 and above hypersensitivity occurred in 2% of patients. Pre-medication prior to each dose is recommended for prevention of infusion reactions and prevention of chemotherapy-induced nausea and vomiting, including antipyretics, H1 and H2 blockers prior to infusion, with corticosteroids used for patients who had prior infusion reactions, and a two or three drug antiemetic combination regimen. TRODELVY is emetogenic, with nausea occurring in 63% of all patients treated with TRODELVY (Grade 3-4 in 4%) and vomiting occurring in 34% of all patients (Grade 3-4 in 3%).

Contraindications

TRODELVY is contraindicated in patients who have experienced a severe hypersensitivity reaction to TRODELVY.

PBS listing

TRODELVY powder for injection 180 mg is listed on the PBS with 4 items, streamlined restriction, and an ex-manufacturer price of A$1484.59.

Regulatory history

TRODELVY sacituzumab govitecan 180 mg powder for injection was first listed on the ARTG on 6 September 2021. An AusPAR was approved on 3 September 2021 for the indication of unresectable locally advanced or metastatic triple-negative breast cancer in adult patients who have received at least two prior systemic therapies, including at least one prior therapy for locally advanced or metastatic disease. The PBAC initially did not recommend TRODELVY in November 2021 but recommended it in March 2022 for unresectable, locally advanced or metastatic triple-negative breast cancer in patients who have received two or more prior therapies. The PBAC did not recommend listing for HR-positive, HER2-negative advanced or metastatic breast cancer in July 2023 and November 2023, noting moderate clinical need and significant improvement in PFS and OS but determining that the ICER remained underestimated and not cost-effective at the proposed price.