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).

Abstract

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.

• Authors: Tufia C Haddad, Jun He, Ciara C O'Sullivan, Beiyun Chen, Donald Northfelt, Amylou C Dueck, Karla V Ballman, Kathleen S Tenner, Hannah Linden, Joseph A Sparano, Judith O Hopkins, Chamath De Silva, Edith A Perez, Paul Haluska, Matthew P Goetz
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 188 Issue 2 Pg. 477-487 (Jul 2021) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 33852121 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)

Chemical References

• Antibodies, Monoclonal, Humanized
• Quinazolines
• Lapatinib
• cixutumumab
• Capecitabine
• Receptor, ErbB-2
• Trastuzumab

Topics

• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Breast Neoplasms (drug therapy)
• Capecitabine (therapeutic use)
• Disease-Free Survival
• Female
• Humans
• Lapatinib (therapeutic use)
• Quality of Life
• Quinazolines (adverse effects)
• Receptor, ErbB-2 (genetics)
• Trastuzumab (therapeutic use)