Abstract P4-01-34: Benefits Provided by Antibody Drug Conjugates in Overall Survival Outweighs those in Progression-free Survival for Metastatic Breast Cancer: A Class Effect

Abstract

Abstract Background: In metastatic breast cancer (MBC), the benefits of progression-free survival (PFS) and overall survival (OS) is not always proportional. This dissociation is related to the multiple other treatment options such as chemotherapy after disease progression and these treatments would contribute to the long post-progression survival. A constant improvement of PFS that translates into OS has been reported in anti-HER2 antibody containing treatments. In the era of antibody drug conjugates (ADC), we aim to examine the relationship between the increments of PFS and OS in MBC. Methods: We have used “ metastatic breast cancer” and “antibody drug conjugate” to search for clinical trials that report both PFS and OS. Hazard ratios (HR) and median survival were analyzed. Increments in PFS (delta PFS) and increments in OS (delta OS) were compared between studies. Results: A total of 5 trials were identified and summarized in table 1. The target of ADC is HER2 (N=4) or Trop2 (N=1). In DESTINY-Breast 03 trial, the control arm is another ADC (T-DM1). The control arms in all the other 4 trials are chemotherapy. The HR of PFS ranged from 0.28 to 0.65 and the HR of OS ranged from 0.48 to 0.68. The HR of PFS is smaller than HR of OS in all of the 5 trials. The median OS was not reached in 1 of the trials (DB-03) and was thus removed from the analysis for delta PFS and delta OS. In the comparison of delta PFS, the increments of median PFS fell between 2.9 and 4.8 months. The increments of median OS were between 5.4 and 6.6 months. All the delta OS are larger than the delta PFS in the four trials.Conclusion: Regardless of the antibody drug targets, ADC provides consistent improvements in median OS that surpasses the improvements in median PFS in metastatic breast cancer. The mechanism warrants further investigation. Citation Format: I-Chun Chen, Ching-Hung Lin, Yen-Shen Lu. Benefits Provided by Antibody Drug Conjugates in Overall Survival Outweighs those in Progression-free Survival for Metastatic Breast Cancer: A Class Effect [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-34.