As antibody-drug conjugates (ADCs) continue to reshape the oncology landscape, leading experts are sharing crucial insights about managing these sophisticated therapeutics. With 14 FDA-approved ADCs now available and more than 100 in development, oncologists are navigating new challenges in implementing these treatments effectively.
Understanding ADC Toxicity Profiles
Dr. Virginia Kaklamani, Chair in Breast Cancer Research at UT Health San Antonio MD Anderson Cancer Center, emphasizes that ADCs' toxicity profiles warrant careful attention. "We've felt for a long time that ADCs have a favorable toxicity profile, but they may not," she notes. Each ADC presents distinct challenges:
- Enhertu (T-DXd): Highly emetogenic with risk of interstitial lung disease
- Trodelvy (sacituzumab govitecan): Notable for neutropenia and diarrhea
- Datroway (datopotamab deruxtecan): Associated with stomatitis
Strategic Implementation and Monitoring
Dr. Rachna T. Shroff, from the University of Arizona Cancer Center, underscores the transformative potential of ADCs while emphasizing the need for strategic implementation. "ADCs are absolutely a new wave of the future in terms of therapeutic development," she states, highlighting the importance of comprehensive genomic profiling to identify suitable targets.
Managing Safety Concerns
Dr. Funda Meric-Bernstam of MD Anderson Cancer Center stresses vigilant monitoring, particularly for specific complications like pneumonitis and interstitial lung disease with T-DXd. She advocates for proactive assessment and early intervention, noting that management protocols may differ from traditional treatment algorithms.
Future Directions and Ongoing Development
Dr. Komal Jhaveri from Memorial Sloan Kettering Cancer Center provides perspective on the evolution of ADC technology. While acknowledging their superiority over conventional chemotherapy, she points to ongoing efforts to optimize these therapies:
- Development of novel payloads
- Exploration of bispecific antibodies
- Investigation of radioligand therapeutics
- Research into immune-stimulating therapeutics
"We're still trying to figure out what we can do to further enhance our understanding of target expression and how to identify that," Dr. Jhaveri explains, emphasizing the continuous pursuit of improved outcomes while managing resistance mechanisms.
Impact on Clinical Practice
The tumor-agnostic approval of T-DXd in 2024 represents a significant milestone in ADC therapy, opening new treatment possibilities across multiple cancer types. This development underscores the importance of comprehensive molecular profiling in treatment planning and highlights the evolving role of ADCs in precision oncology.
