Is a platelet (PLT) count of 75 a contraindication for Kadcyla (ado-trastuzumab emtansine)?

From the Guidelines

A platelet count (PLT) of 75 x 10^9/L is a contraindication for Kadcyla (ado-trastuzumab emtansine) as it increases the risk of bleeding, and Kadcyla should not be administered when platelet counts are below 100 x 10^9/L. This restriction exists because Kadcyla can cause thrombocytopenia (low platelet count), which increases the risk of bleeding. If a patient has a PLT of 75, the healthcare provider should delay Kadcyla treatment until platelet counts recover to ≥100 x 10^9/L. During treatment with Kadcyla, regular monitoring of platelet counts is essential before each dose. If thrombocytopenia develops during treatment, dose modifications or temporary discontinuation may be necessary according to the severity. The mechanism behind Kadcyla-induced thrombocytopenia involves the cytotoxic component DM1, which can affect platelet production in the bone marrow. Patients should be advised to report any unusual bleeding or bruising while on this medication.

Some studies suggest that the risk of bleeding increases as the platelet count decreases, and no clear threshold can be demonstrated 1. However, most experts agree that therapeutic anticoagulation with LMWH may be administered if the platelet count can be maintained above 50 x 10^9/L 1. For platelet counts between 20 and 50 x 10^9/L, half-dose LMWH can be administered with close follow-up for possible bleeding. If platelet count is <20 x 10^9/L, therapeutic doses of anticoagulation should be held.

Key considerations for managing thrombocytopenia in patients with cancer include:

• Identifying and managing current and potential bleeding sources
• Weighing the risk of serious bleeding against the severity of the thrombotic event and risk for recurrent VTE
• Using platelet transfusions to allow anticoagulation in patients with severe cancer- or chemotherapy-induced thrombocytopenia
• Avoiding VKA therapy in patients with severe thrombocytopenia due to the prolonged anticoagulant effect and unpredictable dose response 1.

In the context of Kadcyla treatment, it is essential to prioritize the patient's safety and minimize the risk of bleeding complications. Therefore, delaying Kadcyla treatment until platelet counts recover to ≥100 x 10^9/L is the recommended approach. Regular monitoring of platelet counts and prompt management of thrombocytopenia are crucial to ensuring the safe use of Kadcyla.

From the FDA Drug Label

In the event of decreased platelet count to Grade ≥ 3 (< 50,000/mm3) do not administer KADCYLA until platelet counts recover to Grade 1 (≥ 75,000/mm3) ThrombocytopeniaGrade 2-3 on day of scheduled treatment(25,000 to < 75,000/mm3)Do not administer KADCYLA until platelet count recovers to Grade ≤ 1 (≥ 75,000/mm3), and then treat at the same dose level

• Platelet count of 75,000/mm3 is the threshold for administering KADCYLA.
• A platelet count below 75,000/mm3 requires withholding KADCYLA until the count recovers.
• PLT 75 is not a contraindication for KADCYLA, but rather a threshold for administration. 2

From the Research

Platelet Count and Kadcyla Administration

• A platelet count of 75 × 10^3 per μL is considered thrombocytopenic, as a normal platelet count ranges from 150 × 10^3 per μL to 450 × 10^3 per μL 3.
• Patients with platelet counts between 20 and 50 × 10^3 per μL may have mild skin manifestations such as petechiae, purpura, or ecchymosis, and those with platelet counts of less than 10 × 10^3 per μL have a high risk of serious bleeding 3.
• Kadcyla (ado-trastuzumab emtansine) is a treatment for HER2-positive breast cancer, and its administration can result in thrombocytopenia as a side effect 4, 5, 6, 7.

Thrombocytopenia and Kadcyla

• Thrombocytopenia is a common and potentially serious adverse event of Kadcyla use in patients with advanced breast cancer, with 8%-13% of patients experiencing grade 3-4 thrombocytopenia 5, 6.
• A clinical prediction model has been developed to quantify the personalized risks of thrombocytopenia from Kadcyla usage, which includes factors such as platelet count and race 5.
• The effect of Kadcyla on autologous platelet kinetics and function has been studied, and results show a direct toxic effect of Kadcyla on patients' autologous circulating platelets, leading to decreased platelet survival and function 6.

Contraindications for Kadcyla

• While there is no direct evidence stating that a platelet count of 75 × 10^3 per μL is a contraindication for Kadcyla, patients with thrombocytopenia should be closely monitored for signs of bleeding, and platelet transfusions may be necessary in some cases 3, 5, 6.
• The decision to administer Kadcyla to a patient with a platelet count of 75 × 10^3 per μL should be made on a case-by-case basis, taking into account the patient's individual risk factors and medical history 4, 7.