Treatment of HER2-positive metastatic breast cancer with lapatinib and capecitabine in the lapatinib expanded access programme, including efficacy in brain metastases – the UK experience

Abstract

BACKGROUND:The global lapatinib expanded access programme provided access to lapatinib combined with capecitabine for women with HER2-positive metastatic breast cancer (MBC) who previously received anthracycline, taxane and trastuzumab. METHODS: Progression-free survival (PFS) and safety data for 356 patients recruited from the United Kingdom are reported. Efficacy was assessed in 162 patients from the five lead centres, including objective tumour response rate (ORR), time to disease progression (TTP) and efficacy in those with central nervous system (CNS) metastases. Correlation of PFS and ORR with previous capecitabine treatment was also documented. RESULTS: Overall, PFS for the 356 UK patients was 21 weeks (95% CI: 17.6 -24.7). In the 162 assessable patients, ORR was 21% (95% CI: 15 -27%) and median TTP was 22 weeks (95% CI: 17 -27). Efficacy was greater in capecitabine-naive patients (ORR 23 vs 16.3%, P ¼ 0.008). For 34 patients with CNS metastases, ORR was 21% (95% CI: 9 -39%), with evidence of improvement in neurological symptoms, and median TTP was 22 weeks (95% CI: 15 -28). CONCLUSIONS: Lapatinib combined with capecitabine is an active treatment option for women with refractory HER2-positive MBC, including those with progressive CNS disease.

Lapatinib plus Capecitabine for Brain Metastases in Patients with Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: A Review of the Anatolian Society of Medical Oncology (ASMO) Experience

“…Our retrospective evaluation of safety and efficacy of LC in this population with BMs showed a 27.1% ORR similar to previous experience in the literature [12][13][14][15][16][17]. Moreover, survival outcomes including PFS of 7monthsandOSof13monthsweresimilartotheliterature confirming the efficacy of LC in BMs of HER2+ MBC patients.…”

“…However, it remains unansweredwhetherthehighfrequencyofBMsismerelyrelatedtotheaggressivenessofHER2+disease.Nevertheless, theobservationisveryrelevant,andnovelagentsmoreefficientatpenetratingtheCNStopreventortreatCNSmetastasesareurgentlyneeded.Ithasbeensuggestedthatlapatinib maydecreasetheriskofdevelopingCNSmetastases.InapreclinicalstudybyPalmierietal. [18],lapatinibwasreportedto inhibittheformationofmetastasesinHER2+humanbreast carcinomacells.Inaccordancewiththisobservation,several studies have reported efficacy of LC combination treatment inthispatientpopulation [13][14][15][16][17]. In a phase III study evaluating capecitabine versus LC therapyinMBCpatients,theadditionoflapatinibwasshown tobeassociatedwithareducedincidenceofBMsasthefirst site of relapse, which has been considered as a preventive effect [9,11].…”

Pattern of Rash, Diarrhea, and Hepatic Toxicities Secondary to Lapatinib and Their Association With Age and Response to Neoadjuvant Therapy: Analysis From the NeoALTTO Trial

“…2,3 In addition, it showed interesting activity in patients with brain metastasis. [4][5][6][7] Skin rash, diarrhea, and hepatic toxicities are adverse events (AEs) that have been linked with not only lapatinib, [8][9][10][11] but also other EGFR TKIs.…”

Bevacizumab Preconditioning Followed by Etoposide and Cisplatin Is Highly Effective in Treating Brain Metastases of Breast Cancer Progressing from Whole-Brain Radiotherapy

“…Thus, we were constrained to use contrast-enhanced images for efficacy assessment instead of T2/FLAIRE images. Second, in recent medical literature, volumetric response criteria and RECIST have been used as primary endpoints to evaluate agents in brain metastasis breast cancer patients (7,(24)(25)(26). Because this was a single-arm study, it was critical to use similar assessment criteria to be able to compare with previous study results.…”