Efficacy and Safety of Distamab Vedotin Combined With Carboplatin for Advanced Ovarian Cancer in the First Line Treatment

Ovarian cancer exhibits the highest mortality rate among gynecological malignancies. Currently, the combination of paclitaxel and carboplatin remains the standard first-line chemotherapy regimen for neoadjuvant or postoperative treatment of ovarian cancer. However, conventional paclitaxel, due to the addition of polyoxyethylated castor oil solubilizer, may induce various adverse reactions beyond chemotherapeutic toxicity, such as hypersensitivity, toxic renal injury, neurotoxicity, and cardiovascular toxicity. Therefore, exploring optimized treatment regimens to provide patients with new therapeutic options is imperative. HER2 is a protein encoded by the ERBB2 gene that regulates cell survival, proliferation, and differentiation. HER2 gene amplification and/or protein overexpression are observed in 18%-35% of mucinous ovarian cancers. A meta-analysis involving over 5,000 ovarian cancer cases revealed that HER2 overexpression correlates with reduced overall survival (OS) and progression-free survival (PFS), suggesting its potential as a biomarker for poor prognosis. The emergence of novel antibody-drug conjugates (ADCs) has brought new hope for anti-HER2 therapy in ovarian cancer, such as Disitamab Vedotin (RC48). Preliminary results from the PRaG3.0 trial presented at the 2023 ASCO Annual Meeting showed an ORR of 66.7% in six HER2-expressing gynecological cancer patients treated with RC48 combined with radiotherapy and immune checkpoint inhibitors (ICIs). Updated data from the RC48-C018 study demonstrated an ORR of 36.4%, median duration of response (mDoR) of 5.52 months, mPFS of 4.37 months, and 12-month OS rate of 66% in 22 cervical cancer patients. RC48 exhibited promising efficacy and manageable safety in recurrent/metastatic HER2-expressing (IHC 1+/2+/3+) cervical cancer. Regarding safety, the GOG-158 study reported pronounced hematologic toxicity with carboplatin-paclitaxel in advanced ovarian cancer: grade 3/4 leukopenia (\>50%), thrombocytopenia (\>30%),