Randomized Phase II Trial of Capecitabine and Lapatinib with or without IMC-A12 (Cituxumumab) in Patients with HER2-Positive Advanced Breast Cancer Previously Treated with Trastuzumab and Chemotherapy: NCCTG N0733 (Alliance)

• Published in: Breast cancer research and treatment Vol. 188; no. 2; pp. 477 - 487
• Main Authors: Haddad, Tufia C., He, Jun, O’Sullivan, Ciara C., Chen, Beiyun, Northfelt, Donald, Dueck, Amylou C., Ballman, Karla V., Tenner, Kathleen S., Linden, Hannah, Sparano, Joseph A., Hopkins, Judith O., De Silva, Chamath, Perez, Edith A., Haluska, Paul, Goetz, Matthew P.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-07-2021; Springer Nature B.V
• Subjects: Adverse events; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Breast cancer; Breast Neoplasms - drug therapy; Cancer research; Capecitabine - therapeutic use; Chemotherapy; Clinical Trial; Diarrhea; Disease-Free Survival; ErbB-2 protein; Female; Humans; Lapatinib - therapeutic use; Medicine; Medicine & Public Health; Metastases; Monoclonal antibodies; Oncology; Patients; Quality of Life; Quinazolines - adverse effects; Receptor, ErbB-2 - genetics; Safety; Survival; Targeted cancer therapy; Trastuzumab; Trastuzumab - therapeutic use; Insulin-like growth factor receptor; Metastatic breast cancer; HER2-positive; Trastuzumab-resistance
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-021-06221-8

Purpose
To compare efficacy and safety of capecitabine and lapatinib with or without IMC-A12 (cituxumumab) in patients with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab.
Patients and methods
Following an initial safety run-in cohort, patients were randomized 1:2 to Arm A (capecitabine and lapatinib) or to Arm B (capecitabine, lapatinib, and cituxumumab). Given the frequency of non-hematologic grade ≥ 3 adverse events in those receiving the three-drug combination in the safety cohort, lapatinib and capecitabine doses were reduced in Arm B only. The primary objective was to determine if the addition of cituxumumab to capecitabine and lapatinib improved progression-free survival (PFS) compared with capecitabine and lapatinib. Secondary objectives included a comparison between arms of other clinical endpoints, safety, change in overall quality of life (QOL) and self-assessed fatigue, rash, diarrhea, and hand-foot syndrome.
Results
From July 2008 to March 2012, 68 patients (out of 142 planned) were enrolled and 63 were evaluable, including 8 for the safety run-in and 55 for the randomized cohort. Study enrollment was stopped early due to slow accrual. The addition of cituxumumab to capecitabine and lapatinib did not improve PFS (HR 0.93, 95% CI: 0.52–1.64). Furthermore, no difference in objective response rate or overall survival (OS) was observed. No difference between arms was observed in grade ≥ 3 adverse events, overall QOL change from baseline after 4 cycles of treatment.
Conclusion
The addition of cituxumumab to lapatinib and capecitabine did not improve PFS or OS compared with lapatinib and capecitabine in patients with HER2-positive MBC.
Clinical trial registry
ClinicalTrials.gov Identifier: NCT00684983