A trial for a new Nectin-4 ADC was amended to include mandatory, prospective CYP2D6 genotyping after a few patients experienced life-threatening toxicities. This highlights the growing importance of pharmacogenomics for ensuring the safety of novel ADCs.

A critical but easily missed safety issue with the ADC enfortumab vedotin (EV) is its risk of severe hyperglycemia. The drug is formally contraindicated in patients with a hemoglobin A1c above 8%. Clinicians must screen for this to prevent potentially fatal ketoacidosis.

Anemia is an on-target, expected side effect of the HIF2-alpha inhibitor belzutafan. Experienced clinicians proactively manage this by starting erythropoietin-stimulating agents (ESAs) when hemoglobin falls below 9 g/dL, and sometimes place the order preemptively to avoid treatment delays.

Clinical evidence suggests a critical 48- to 60-hour window for administering glucarpidase post-methotrexate infusion. Once irreversible organ injury occurs, the drug's benefit is significantly reduced. This narrow timeframe underscores the need for rapid diagnosis and intervention.

For patients who achieve a deep response to a PARP inhibitor but struggle with persistent hematologic toxicity despite dose reductions, a practical clinical strategy is to switch to a different agent within the same class (e.g., from olaparib to rucaparib). This may offer a chance for improved tolerability while maintaining therapeutic benefit.

Combining KRAS G12C inhibitors with checkpoint inhibitors increases the risk of transaminitis. Differentiating the causative agent is clinically challenging. A rapid recovery after stopping both drugs suggests the KRAS inhibitor is the cause and can be restarted at a lower dose; slower recovery points to the immunotherapy.

Eltrombopag is a potent iron chelator that can cause or worsen iron deficiency. In ITP patients with existing iron deficiency, alternative TPO receptor agonists like avatrombopag or romiplostim, which do not chelate iron, should be used instead.

Due to limited and delayed availability of endocrinologists, oncologists must be comfortable with the frontline management of metabolic side effects like hyperglycemia. This involves aggressive monitoring from the start and initiating treatment themselves, a necessary skill for effectively using drugs like Capivasertib, especially in practices outside the U.S.

A patient's diabetes must be well-managed before starting the inavolisib triplet, with an HbA1c below 8. The pivotal trial used an even stricter cutoff of 6.0. Proactive management, including consideration of continuous glucose monitoring, is critical to prevent severe hyperglycemia, a major toxicity of this effective regimen.