Lapatinib plus Capecitabine versus Trastuzumab plus Capecitabine in the Treatment of Human Epidermal Growth Factor Receptor 2-positive Metastatic Breast Cancer with Central Nervous System Metastases for Patients Currently or Previously Treated with Trastuzumab (LANTERN): a Phase II Randomised Trial

• Published in: Clinical oncology (Royal College of Radiologists (Great Britain)) 2020-10, Vol.32 (10), p.656-664
• Main Authors: Seligmann, J.F., Wright-Hughes, A., Pottinger, A., Velikova, G., Oughton, J.B., Murden, G., Rizwanullah, M., Price, C., Passant, H., Heudtlass, P., Marshall, H., Johnston, S., Dodwell, D.
• Format: Article
• Language: English
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Brain metastases; breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Capecitabine - administration & dosage; Central Nervous System Neoplasms - drug therapy; Central Nervous System Neoplasms - metabolism; Central Nervous System Neoplasms - secondary; Female; HER2; Humans; lapatinib; Lapatinib - administration & dosage; Middle Aged; Prognosis; radiotherapy; Receptor, ErbB-2 - metabolism; Salvage Therapy; Survival Rate; trastuzumab; Trastuzumab - administration & dosage
• ISSN: 0936-6555; 1433-2981
• DOI: 10.1016/j.clon.2020.06.003

Brain (central nervous system; CNS) metastases occur in 30–50% of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). A substantive evidence base for treatment is lacking, but activity with lapatinib plus capecitabine (lap-cap) has been reported. We compared lap-cap with trastuzumab plus capecitabine (tras-cap) in patients with HER2-positive MBC with CNS metastases previously treated with trastuzumab. This open-label randomised phase II screening trial aimed to randomise 130 participants over 2 years to receive lap-cap or tras-cap. Eligible patients had HER2-positive MBC with newly diagnosed or recently progressed CNS metastases; previous, or current, treatment included: trastuzumab, a taxane or anthracycline and recent completion of local cranial therapy. The primary end point was time to progression of CNS metastases within the 24-week trial period. Secondary objectives included CNS response rate, progression-free survival, steroid use for CNS symptoms and feasibility of recruitment to a large phase III trial. Between September 2011 and October 2013, 30 participants were randomised, 16 to lap-cap and 14 to tras-cap. Recruitment to a large phase III trial was determined not to be feasible. At 24 weeks, CNS disease progression was 41.8% (95% confidence interval 16.1–67.5%) in lap-cap and 41.2% (95% confidence interval 12.8–69.6%) in tras-cap arms; progression-free survival was 44.4% (95% confidence interval 18.1–70.8%) in lap-cap and 50.0% (95% confidence interval 20.9–79.1%) in tras-cap arms. Poor recruitment confirmed that a larger phase III trial would not be feasible and prohibited a preliminary evaluation of the superiority of lap-cap over tras-cap. Descriptive statistics are presented to inform the limited evidence base and future study design. •Recruitment was challenging and conclusions are limited.•An encouraging response rate with acceptable toxicity were observed for trastuzumab and capecitabine.•Robust evidence for both trastuzumab and lapatinib treatment options in this population is still required.