Effectiveness and safety of disitamab vedotin (RC48) in pretreated HER2-positive advanced breast cancer: A real-world experience in China.

e13022 Background: The optimal treatment of HER2-positive advanced breast cancer (ABC) in later lines of therapy remains undefined, especially after progression on previous monoclonal antibodies and tyrosine kinase inhibitors (TKI). Disitamab vedotin (RC48) is a novel self-developed, HER2-targeting ADC drug comprised of hertuzumab coupling monomethyl auristatin E (MMAE) via a cleavable linker in China. This study aims to evaluate the effectiveness and safety of RC48 in previously treated HER2+ ABC patients in the real-world setting. Methods: This is a nationwide, observational cohort study conducted in 21 sites in China. Patients with HER2+ABC who received RC48 treatment were included. Demographics, treatment patterns, clinical outcomes and safety information were examined. Real-world progression-free survival (PFS) and overall survival (OS) were analyzed. Results: From June 2021 to October 2023, a total of 60 patients meeting study criteria were included, with a median age of 51 (45-59) years. 98.33% of all patients were female. Among all, 56.67% were hormone receptor positive. All patients received prior anti-HER2 TKI therapy and 96.67% were trastuzumab pretreated. Anti-microtubule chemotherapy was given in 81.67% of patients. RC48 were used as monotherapy in 75% of patients, and 25% of them received combination therapy. The median number of RC48 treatment line was three (2nd-line to 13th-line), and the median RC48 treatment duration was 4.24 months (IQR: 2.68-7.99). The median PFS was 7.85 months (95% CI: 4.44-9.59). The overall ORR and DCR was 26.8% (95% CI: 15.8%-40.3%) and 73.2% (95% CI: 59.7%-84.2%), respectively. The median DoR of the 15 cases with objective response was 5.78 months. In subgroup analysis, a significant longer mPFS was observed in combined use of RC48 and other targeted therapy/anti-angiogenic therapy compared with RC48 monotherapy (NE vs. 4.99 months, p=0.012). No significant survival differences were observed in patients with or without prior anti-microtubule chemotherapy or among different RC48 treatment lines (Table). The most common adverse events of grade 3 or higher was decreased blood cell count (11.67%); AST elevation (10.00%). Conclusions: RC48 showed a promising antitumor activity and acceptable tolerability in this pretreated patient population with HER2-positive ABC. The combination of RC48 with other targeted therapy might be a potential treatment option. Fresh prior chemotherapy with anti-microtubule drugs does not seem to affect the efficacy of RC48 while further studies with larger sample size are needed. Efficacy summary. median PFS, mo (95% CI) Overall (n=60) 7.85 (4.44-9.59) RC48 treatment lines≤3 (n=31)>3 (n=29) 8.00 (4.44-NE)5.95 (4.01-8.97) RC48 treatment patternMono (n=45)Com (n=15) 4.99 (4.00-8.00)NE (4.60-NE) Prior anti-microtubule therapyYes (n=49)No (n=11) 7.85 (4.30-13.90)7.00 (2.96-8.00)