Efficacy and safety of antibody-drug conjugates in triple-negative and HER-2 positive breast cancer: A systematic review and meta-analysis of clinical trials

Article type: Systematic Review

Authors: Afzal, Fatima^a; | Aiman, Wajeeha^b; | Zahoor, Hafsa^c; | Bajwa, Ayfa Riaz^d | Kazmi, Syeda Hafsa^e | Anwar, Aqsa^f | Anwar, Muhammad Yasir^c | Rashid, Sana^g | Zubair, Hina^h | Kashif, Toobaⁱ | Ashar Ali, Muhammad^j;

Affiliations: [a] Schulich School of Medicine and Dentistry, University of Western Ontario, Ontario, Canada | [b] Saint Michael’s Medical Center, New York Medical College, Newark, NJ, USA | [c] BronxCare Health System, Bronx, NY, USA | [d] Punjab Medical College, Faisalabad, Pakistan | [e] Dr. V.R.K. Women’s Medical College, Hyderabad, India | [f] Ameer-ud-din Medical College, Lahore, Pakistan | [g] Baqai Medical College, Karachi, Pakistan | [h] Rawalpindi Medical College, Rawalpindi, Pakistan | [i] Dow University of Health Sciences, Karachi, Pakistan | [j] PHCC at Saint Clare’s and Saint Mary’s General Hospitals, Denville, NJ, USA

Correspondence: [*] Corresponding author: Muhammad Ashar Ali, PHCC at Saint Clare’s and Saint Mary’s General Hospitals, 25 Pocono Rd, Danville, NJ, USA. Tel.: +1 857 3708113; E-mail: [email protected], [email protected]

Note: [†] Equal contribution for the first authorship.

Abstract: Breast cancer (BC) is the 2nd most common cause of cancer-related deaths. Antibody-drug conjugates (ADCs) are monoclonal antibodies linked to cytotoxic agents and are directed towards a specific tumor protein. Therefore, they are more potent and can have relatively less toxicity. In this meta-analysis, we assessed the efficacy and safety of ADCs in breast cancer. We searched PubMed, Cochrane, Web of Science, and clinicaltrials.gov for relevant studies and included 7 randomized clinical trials (N = 5,302) and 7 non-randomized clinical trials (N = 658). R programming language software was used to conduct this meta-analysis. In 4 RCTs on HER-2 positive BC (N = 2,825), the pooled HR of PFS and OS was 0.72 (95% CI = 0.61–0.84, I2 = 71%) and 0.73 (95% CI = 0.64–0.84, I2 = 20%), respectively in favor of ADCs versus chemotherapy. In RCT on triple negative BC (N = 468), HR of PFS and OS were 0.55 (95%CI = 0.51–0.61) and 0.59 (95% CI = 0.54–0.66), respectively, in favor of saci-gov versus chemotherapy. In RCT on HER-2 positive residual invasive BC, HR of recurrence/death was 0.61 (95% CI = 0.54–0.69) in favor of ADC versus chemotherapy. In an RCT (N = 524), the HR of PFS and OS were 0.28 (95% CI = 0.22–0.37) and 0.55 (95%CI = 0.36–0.86), respectively, in favor of trastuzumab-deruxtecan (T-der) as compared to trastuzumab-emtansine (T-DM1). Anemia, rash, diarrhea, fatigue, hypertension, thrombocytopenia, and elevated aminotransferases were the common ≥grade 3 adverse events reported in 4%, 1%, 2%, 1%, 2%, 9%, and 3% of the patients, respectively. ADCs were more effective than single and double agent chemotherapy in patients with HER-2 positive or triple negative BC. Among ADCs, T-der was more effective than T-DM1.

Keywords: Breast cancer, antibody-drug conjugates, trastuzumab-emtansine, trastuzumab-deruxtecan, sacituzumab govitecan

DOI: 10.3233/BD-220052

Journal: Breast Disease, vol. 42, no. 1, pp. 121-136, 2023