How would you manage a patient who develops acute stroke during neoadjuvant chemotherapy with KEYNOTE-522 for Stage III triple negative breast cancer?

I will try to provide some data for discussion, but also welcome comments from other experts and opinions. I'm assuming this is a younger patient without known risk factors and that an assessment for things like A. Fib, PFO, and DVT have been performed.

Chemotherapy has long been associated with thrombosis and cancer, with varying agents having a tighter association (Herrmann et al., PMID 27022039; Saphner et al., PMID 1988575). ICI therapy has had a retrospective, and it appears that CTLA-4 therapy carries the greater weight (Jain et al., Journal for ImmunoTherapy of Cancer 2020). The risk of cancer and hypercoagulable state is also well established, and I won't go into too much detail with that other than to say it is more associated with VTE but can certainly lead to arterial events as well. There is a huge body of literature on the effects of cancer and the clotting cascade and endothelial effects.

When one looks at the components of KEYNOTE-522, it is interesting to note that the platinum agents seem to carry a known risk for thromboembolic events, first noted in cisplatin but also identified in carboplatin (Kim et al., PMID 29228042). 

So, I would think the following: the risk of untreated triple negative breast cancer is very significant. What is the risk of another significant stroke here versus dying from cancer? What is unknown is what factors caused the stroke in this patient. Yet, I think continued treatment is important if they haven't already had most of their therapy and had a great clinical response (in that case, I think you can consider just being done but I'm assuming this isn't the case).

If the cancer is causing hypercoagulability, then killing the tumor usually improves things. Looking at the chemotherapy, I think the platinums, in particular, carry known risk, and you could consider at least abandoning this and move forward with the other components. If the risk of anticoagulation is not too great, then I would also consider giving some prophylactic anticoagulation with LMWH or a DOAC and consider baby ASA with a close eye on platelet count nadirs. This is a bit data-free, but there is some evidence that stroke in cancer patients was reduced with these agents over VKA (Bang et al., PMID 32027788).

I would say "Talk to your hematologist" but many reading this also wear that hat and can evaluate the literature themselves and consider the risks/benefits of anticoagulation. Looking forward to other thoughts in this arena.