Abstract
The purpose of the present study was to quantify the cumulative randomized evidence for the efficacy and safety of lapatinib combined with neoadjuvant therapy in human epidermal growth factor receptor (HER) 2-positive breast cancer. Three electronic databases, MEDLINE, Embase and Cochrane Central Register of Controlled Trials, and the abstracts of major international conferences between inception and 15 December 2013 were searched. Two evaluators independently extracted data. The end-points assessed consisted of the pathological complete response (pCR) rate, breast-conserving surgery (BCS) rate and the occurrence of adverse events. Four randomized controlled trials were assessed in the present study, involving a total of 779 participants. Compared with the patients who did not receive lapatinib, the pCR rate was higher in the hormone receptor (HR)-positive [risk ratio (RR), 1.39; 95% confidence interval (CI), 1.12–1.72; P=0.002) and HR-negative (RR, 1.38; 95% CI, 1.14–1.68; P=0.0009) patients that received lapatinib. No significant difference between the BCS rate of the two treatment arms was observed in two trials (n=382; RR, 1.14; 95% CI, 0.89–1.47; P=0.31). The primary adverse events, including diarrhea, dermatological toxicity, hepatic toxicity and neutropenia, were statistically more frequent in patients that received lapatinib (RR, 2.46; 95% CI, 1.97–3.07; P<0.00001). The present analysis revealed that the addition of lapatinib to neoadjuvant chemotherapy for HER2-positive breast cancer improves the probability of achieving a higher pCR rate, but the use of lapatinib is associated with a higher risk of adverse events.
Highlights
Neoadjuvant chemotherapy for the treatment of breast cancer has been reported to be equivalent to adjuvant chemotherapy in terms of survival and overall disease progression [1]
The present study, with the inclusion of all available randomized controlled trials (RCTs) regarding lapatinib combined to neoadjuvant therapy, provides evidence that the addition of lapatinib to neoadjuvant chemotherapy in HER2‐positive breast cancer patients results in a significant increase in the pathological complete response (pCR) rate
Neoadjuvant studies using anti‐HER2 agents have revealed that the pCR rate is correlated with disease‐free survival [16,17]
Summary
Neoadjuvant chemotherapy for the treatment of breast cancer has been reported to be equivalent to adjuvant chemotherapy in terms of survival and overall disease progression [1]. Neoadjuvant chemotherapy offers certain attractive benefits, since it can downstage the primary tumor in the majority of patients, increasing breast‐conserving surgery (BCS) rates or improving resectability [2]. Combined with neoadjuvant chemotherapy for the treatment of HER2‐positive breast cancer patients, trastuzumab offers a substantial benefit in terms of pCR, with no additional toxicity [5]. As demonstrated by cell line and xenograft models [6,7], lapatinib blocks the activating signaling cascades in the MAPK and PI3K pathways, resulting in cell growth arrest or apoptosis. Clinical trials have demonstrated that lapatinib is efficacious in HER2‐positive metastatic breast cancer [8]
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