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

e13006 Background: The optimal treatment for HER2-positive advanced breast cancer (ABC) in later lines remains unclear, particularly after progression on monoclonal antibodies and tyrosine kinase inhibitors (TKIs). Disitamab vedotin (RC48) is a novel HER2-targeted antibody-drug conjugate (ADC) composed of hertuzumab coupled with monomethyl auristatin E (MMAE) via a cleavable linker. This study aimed to evaluate the efficacy and safety of RC48 in real-world HER2+ ABC patients. Methods: This nationwide, observational cohort study was conducted at 22 sites in China. Patients with HER2+ ABC who received RC48 treatment were included. Demographics, treatment patterns, clinical outcomes, and safety data were analyzed. Real-world progression-free survival (PFS) and overall survival (OS) were assessed. Results: From June 2021 to October 2023, 67 patients were enrolled, with a median age of 51 (45-59) years. 98.33% of all patients were female. Among all, 59.70% had hormone receptor-positive tumors. All patients had received prior anti-HER2 TKI therapy and 96.67% were anti-HER2 monoclonal antibodies pretreated. Anti-microtubule chemotherapy was given in 82.09% of patients, 80.00% of whom achieved disease control as best overall response (BOR). The median number of RC48 treatment lines was three (2nd to 13th-line), with a median treatment duration of 4.07 months (IQR: 2.56-7.98). Median PFS was 7.85 months (95% CI: 4.60-9.59), consistent with previous studies. The overall ORR and DCR were 27.4% (95% CI: 16.9%-40.2%) and 72.6% (95% CI: 59.8%-83.2%), respectively. The median duration of response (DoR) for the 17 responders was 5.78 months. The median PFS of patients who received RC48 as > 3 lines of treatment was 5.95 months (95% CI: 4.01-8.84). No statistical differences were found across subgroups based on prior anti-microtubule chemotherapy, regardless of BOR or RC48 continuity (Table). Grade ≥3 adverse events occurred in 23.88% of patients. The most common was decreased white blood cell count (8.95%). Conclusions: RC48 showed promising antitumor activity and manageable tolerability in this heavily pretreated HER2+ ABC population, offering a reasonable option for later-line treatment in clinical practice. Prior chemotherapy with anti-microtubule agents did not seem to affect RC48 efficacy in our study, while further studies with larger sample sizes are still needed. Clinical trial information: ChiCTR2500095450 . Efficacy summary. Median PFS, mo (95% CI) Overall (n=67) 7.85(4.60-9.59) RC48 treatment lines≤3 (n=35)>3 (n=32) 8.00(4.86-16.16)5.95(4.01-8.84) Prior anti-microtubule therapyYes (n=55)No (n=12) 7.85 (4.60-14.46)7.00(2.96-8.00) BOR in prior anti-microtubule therapyDisease control (n=44)Disease progression (n=11) 8.84(4.30-14.46)6.70(1.28-16.16) Continuity between prior anti-microtubule therapy and RC48Yes (n=33)No (n=22) 9.76(4.00-16.36)7.85(4.17-13.90)