Risk of VTE in TNBC treated with neoadjuvant immunotherapy.

Abstract

e12658 Background: Triple-negative breast cancer (TNBC) has limited treatment options. KEYNOTE 522 led to the approval of neoadjuvant (NT) Pembrolizumab in July 2021 changing the treatment paradigm for early stage TNBC. While improving pathologic complete response it also slightly increased treatment related adverse events. Some studies show increased risk of venous thromboembolism (VTE) with Pembrolizumab; however, it is unclear if immunotherapy (IO) increases the risk of VTE in a NT setting. Breast cancer is not classically associated with high risk for VTE. Here, we assess the incidence of VTE in TNBC patients receiving NT Pembrolizumab. Methods: All women diagnosed with TNBC and treated with NT Pembrolizumab between August 2021-December 2023 (t = 29 months) at our institution were included (N = 26). Stage 4 disease at time of diagnosis was excluded. The study endpoint was the development of VTE at any time following the initiation of Pembrolizumab as identified by CT chest angiography or venous duplex ultrasound. Risk factors and protective factors for VTE including body mass index, prior VTE, concurrent chest port, illicit drug use, smoking, hypertension, diabetes, kidney disease, hyperlipidemia, and prior antiplatelet/anticoagulant use were assessed for each patient. Results: In our study population, 1 patient developed VTE following initiation of Pembrolizumab (3.8%). This patient developed a pulmonary embolism 13 days after the 2nd dose of Pembrolizumab (179 days after 1st dose). Risk factors for this patient were obesity (BMI = 52.9), concurrent chest port, and hypertension. Protective factors included no prior history of VTE, illicit drug use, smoking, diabetes, kidney disease, or hyperlipidemia. A comparison of the risk factors is summarized (Table). Conclusions: The cumulative VTE incidence for all immune therapies is reported as 7-10% in the 1st year. Patients with breast cancer have a 6% incidence of VTE in the 1st year. This rate does not account for cancer subtype, stage, or treatment type. Our exploratory study is novel in looking at incidence of VTE in the NT immunotherapy use setting. These results suggest a lower incidence compared to the cumulative studies previously mentioned. There is a possible synergistic interaction between Pembrolizumab therapy and other traditional risk factors in the development of VTE in TNBC. Further analysis will seek to stratify the individual risk of Pembrolizumab in VTE compared to other risk factors. Future work will include expanding our study population to additional solid tumors utilizing NT Pembrolizumab including melanoma and non-small cell lung carcinoma. Once risk is definitively established, it will be important to take measures to mitigate the risks to improve cancer related outcomes. [Table: see text]