When Does Acceptable Become Unacceptable? Toxicities of Emerging Therapies

Novel systemic anticancer therapies, including immune checkpoint inhibitors (ICIs), antibody-drug conjugates (ADCs), bispecific antibodies, and next-generation targeted agents, have improved survival, expanded into earlier disease settings, and created a growing population of long-term survivors. However, these therapies introduce toxicity profiles that differ substantially from those of traditional cytotoxic chemotherapy, including differences in organs affected, timing of onset, management strategies, and long-term sequelae. Tailored approaches to monitoring, diagnosis, and treatment are therefore required, along with stronger evidence to guide strategies that reduce morbidity and mortality while maintaining antitumor efficacy. Importantly, patients' lived experiences of toxicity often do not align with clinician-graded Common Terminology Criteria for Adverse Events classifications. Nonobservable symptoms, daily functioning, and quality of life must also be taken into account. Here, ocular and cutaneous adverse events are used as illustrative examples of how toxicities that may appear mild can become unacceptable when they impair function, quality of life, or treatment sustainability. Interdisciplinary collaboration between oncologists and organ specialists is essential for optimal recognition and management. At the same time, the evidence base for toxicity risk and management must continue to evolve through registries such as Side Effect Registry Immuno-Oncology and prospective comparative studies. Better tailored treatment strategies, particularly for immune-related adverse events, are needed to preserve both tumor response and organ function while reducing reliance on corticosteroids and broad immunosuppression. Although these therapies are highly effective, their risks must be better understood and managed to maximize patient benefit.