EGFR mutated NSCLC: Treatment Advances and Highlights from ASCO 2025 - Episode 7
FLAURA2 and MARIPOSA: Expert Insights on Safety Outcomes
Panelists discuss the evolving safety profiles of first-line EGFR-mutated lung cancer treatments, highlighting that chemotherapy combinations cause expected hematologic toxicities and fatigue, while bispecific antibody regimens bring unique challenges such as infusion reactions, more severe rashes and diarrhea, peripheral edema, and a notably increased risk of venous thromboembolism that warrants prophylactic anticoagulation and careful patient monitoring.
Over the past year, the first-line treatment landscape for EGFR-mutated lung cancer has become increasingly complex, especially with the introduction of combination therapies. Both chemotherapy-based regimens and bispecific antibody regimens use a third-generation EGFR TKI as their backbone, which generally results in mild side effects such as rash and diarrhea, along with the need for ongoing cardiac monitoring. The chemotherapy-containing regimen typically causes more hematologic toxicities, such as low blood counts, and increases fatigue early in treatment due to the chemotherapy doublet. These side effects are well known and manageable within thoracic oncology teams experienced in combining chemotherapy with targeted agents.
In contrast, the newer bispecific antibody-containing regimen presents a different safety profile. Infusion reactions are a notable risk during the initial administration, but treatment teams have become adept at recognizing and managing these reactions. Later on, patients tend to experience more significant rashes, sometimes involving the scalp, and more severe diarrhea due to increased inhibition of the EGFR pathway. These toxicities require close monitoring and supportive care to maintain patients’ quality of life throughout therapy. The antibody therapy also introduces additional side effects not commonly seen with chemotherapy, including peripheral edema related to the mechanism of action of the drug.
A particularly important safety concern with the bispecific antibody regimen is the increased risk of venous thromboembolism (VTE). This risk is significantly higher compared to the chemotherapy-based approach, leading to recommendations for prophylactic anticoagulation, typically with direct oral anticoagulants (DOACs), for at least the first four months of treatment. This proactive approach aims to protect patients during the period of highest vulnerability to clotting events. Ultimately, these differences in side effect profiles and scheduling necessitate careful patient selection and individualized monitoring strategies to balance efficacy with safety in clinical practice.
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