The treatment paradigm for platinum-resistant ovarian cancer is undergoing significant changes with the integration of novel antibody-drug conjugates (ADCs) and a more nuanced understanding of platinum resistance, according to Kathleen N. Moore, MD, MS, of the University of Oklahoma College of Medicine.
Evolving Definition of Platinum Resistance
Traditionally, platinum resistance has been strictly defined as tumor progression within 6 months of the last platinum-based treatment. However, this definition is evolving to include tumors that do not respond to platinum initially or progress during PARP inhibitor maintenance. "There's an increasing understanding of these nuances," Moore noted, highlighting that tumors progressing on PARP inhibitors may exhibit reduced sensitivity to subsequent platinum-based therapies.
Key Updates in Advanced Ovarian Cancer
Recent developments include the FDA approval of mirvetuximab soravtansine for patients with platinum-resistant, folate receptor-alpha (FRα)-high ovarian cancer. This ADC has demonstrated improvements in progression-free survival, overall survival (OS), and overall response rate (ORR). Additionally, weekly paclitaxel, with ORRs ranging from 30% to 50%, is emerging as a preferred regimen, especially for patients with FRα-low or medium tumors.
Novel ADCs in Development
Several ADCs with different targets, payloads, and linker technologies are in late-phase clinical trials. Raludotatug deruxtecan (DS-6000), targeting CDH6 with a deruxtecan payload, is currently in phase 2/3 testing. Rinatabart sesutecan (PRO1184), another FRα-targeted ADC with an exatecan payload, is also under development. These camptothecin payloads differ from the microtubule toxin payloads like mirvetuximab soravtansine, potentially allowing for sequential use.
Other ADCs, such as TROP2-directed ADCs and TORL-1-23 (targeting Claudin-6), are also showing promise in early-phase trials. These agents are vying for a spot in the ovarian cancer treatment paradigm, potentially leading to significant shifts in treatment sequencing and incorporation into earlier lines of therapy.
Future Directions
Looking ahead, there is interest in evaluating ADCs head-to-head with platinum in the platinum-sensitive setting and exploring their use as maintenance therapy. However, challenges remain regarding long-term tolerability, potential resistance mechanisms, and optimal sequencing strategies. The integration of these novel ADCs promises to reshape the treatment landscape for ovarian cancer, offering new hope for patients across different stages of the disease.
