Adverse Event Management Strategies for FLAURA2 and MARIPOSA: Expert Insights and Best Practices

In clinical practice, managing patients on the chemotherapy plus osimertinib regimen involves familiarity with the known side effects of pemetrexed, which has been used for many years. The initial four cycles of platinum-based chemotherapy combined with osimertinib often cause some hematologic toxicities, but these are generally manageable and do not usually require routine prophylaxis for neutropenia. After completing the combination cycles, the toxicity profile typically improves as patients continue on pemetrexed maintenance with osimertinib alone, leading to fewer side effects such as fatigue or blood count issues. Rash and diarrhea related to EGFR inhibition tend to be most prominent in the first two to three months but often become less severe over time, although occasional flares can occur. Regular monitoring of liver function and blood counts in the early weeks is critical, and patient adherence to oral medications must be closely supported to ensure optimal treatment outcomes.

For patients receiving the bispecific antibody-containing regimen, there is a distinct approach to toxicity management. Key adverse events include infusion-related reactions, which usually occur during the first treatment cycle but become less frequent with subsequent infusions. Pre-medication protocols such as corticosteroid prophylaxis starting days before treatment have been effective in reducing the severity of these reactions. Another major concern is the elevated risk of venous thromboembolism (VTE), which necessitates prophylactic anticoagulation for the initial months of therapy to protect patients during their most vulnerable period. Patient education about these risks and the importance of compliance with prophylaxis is essential for safety.

Rash management is often the most challenging aspect of the bispecific antibody regimen, particularly when it involves severe scalp rash that can significantly affect quality of life. Close collaboration with dermatology specialists allows for timely interventions using antibiotics and topical therapies to control symptoms and prevent dose interruptions whenever possible. Preparing patients with clear information about what to expect and how side effects will be managed helps reduce anxiety and supports long-term adherence to treatment. Overall, proactive toxicity monitoring and multidisciplinary care are key to successfully supporting patients on these evolving therapeutic regimens.