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Dr Timothy Yap: PARP/TOP1 Inhibitor Toxicities Can Be Managed Through Targeted Delivery


Targeted tumor delivery of irinotecan through sacituzumab govitecan can help to reduce treatment-related toxicities, noted Timothy A. Yap, MBBS, PhD, FRCP, medical director of the Institute for Applied Cancer Science, MD Anderson Cancer Center.

Following initial presentation of SEASTAR trial data on the novel combination of sacituzumab govitecan plus rucaparib, which was investigated for use in metastatic triple-negative breast cancer and other advanced/metastatic solid tumors (ie, platinum-resistant ovarian cancer, urothelial cancers), at this year’s annual virtual European Society for Medical Oncology (ESMO) meeting, Timothy A. Yap, MBBS, PhD, FRCP, medical director, Institute for Applied Cancer Science, the University of Texas MD Anderson Cancer Center, discusses with The American Journal of Managed Care® the toxicities associated with this treatment and how they were managed in the investigative setting.


How do the clinical toxicities from PARP and TOP1 inhibitors affect treatment?

Clinically, PARP inhibitors, such as rucaparib, and TOP1 inhibitors, such as irinotecan, have shown highly synergistic antitumor effects. But as noted in our ESMO presentation, clinical development of this combination has been hampered by overlapping toxicities, and these overlapping toxicities chiefly comprise myelosuppression, gastrointestinal symptoms, and fatigue. This arm of the SEASTAR study was designed to explore whether a targeted tumor delivery of the TOP1 inhibitor irinotecan through the use of sacituzumab govitecan as part of that could actually reduce the systemic toxicity of the combination. And the toxicities we observed in the study were effectively managed through dose modification and or hemopoietic growth factor support, and together with the initial encouraging signals of antitumor activity suggests that further study of this combination is warranted.

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