If a patient's HER2-positive advanced breast cancer has progressed during or after second-line or greater HER2-targeted treatment...Recommendation…May offer lapatinib and trastuzumab...

HER2-Positive and postmenopausal or premenopausal receiving ovarian ablation or suppression: Aromatase inhibitor ± lapatinib + trastuzumab.

HER2-positive breast cancer...Recommendations...Second-line treatment...lapatinib is an evidence-based therapy option to be used preferably in combinations (e.g. with capecitabine, trastuzumab or ET)...

Three hundred five women with untreated stage II and III HER2-positive breast cancer were randomly assigned to receive weekly paclitaxel combined with trastuzumab plus lapatinib (THL), trastuzumab (TH), or lapatinib (TL)….THL had significantly better RFS and OS than did TH (RFS hazard ratio, 0.32; 95% CI, 0.14 to 0.71; P = .005; OS hazard ratio, 0.34; 95% CI, 0.12 to 0.94; P = .037), with no difference between TH and TL....In CALGB 40601, dual HER2-targeting resulted in significant RFS and OS benefits.

NON SUPPORTIVE: Four hundred fifty-five patients with HER2-positive early breast cancer randomly received L 1500 mg/day (n = 154), T (common dose, n = 149) or L 1000 mg/day plus T (n = 152) for 6 weeks, followed by the assigned anti-HER2 treatment combined with paclitaxel weekly × 12. Six-Year OS rates were 82%, 79% and 85% for L, T and L + T, respectively (L vs T: HR, 0.85 [95% CI, 0.49-1.46; P = .56]; L + T vs T: HR, 0.72 [95% CI, 0.41-1.27; P = .26]).

EGF104900, a phase III, randomized, multicenter, open-label study, was designed to compare the efficacy and safety of lapatinib alone with lapatinib in combination with trastuzumab in patients with ErbB2-positive MBC who had experienced progression on prior trastuzumab-based therapy....The combination of lapatinib with trastuzumab provided a statistically significant improvement in PFS compared with single-agent lapatinib, with an HR of 0.73 (95% CI, 0.57 to 0.93; P = .008; Fig 2). The median PFS was 8.1 weeks with lapatinib alone compared with 12.0 weeks with the combination treatment.

All patients were treated with neoadjuvant trastuzumab (n=568) in combination with multi-agent chemotherapy (n=282), a single taxane (n=286), pertuzumab (n=264), lapatinib (n=103) or without a second anti-HER2 drug (n=201)….HER2DX pCR as continuous score was significantly associated with pCR in all patients (odds-ratio [OR]=1.62, 95% CI 1.43-1.85; AUC=0.75), in patients treated with trastuzumab and chemotherapy (OR=1.48, 1.18-1.86) and in patients treated with dual HER2 blockade and chemotherapy (OR=1.69, 1.50-1.91)....HER2DX might help identify patients with HER2-positive breast cancer who benefit from neoadjuvant dual HER2 blockade in combination with a single taxane.

We determined whether trastuzumab plus lapatinib or lapatinib therapy is not inferior to trastuzumab therapy in HER2-positive breast cancer patients….Trastuzumab combined with lapatinib therapy was found to be superior to standard trastuzumab therapy alone with regard to overall survival, disease-free survival/event-free survival, pathologic complete response (ypT0/is ypN0), pathologic complete response (ypT0/is ypN0/+), recurrence-free survival....The efficacy of trastuzumab combined with lapatinib therapy is superior to standard trastuzumab therapy alone...

...prospective translational research study in stage I-IIIA HER2+ breast cancer designed to evaluate the ability of the PAM50 intrinsic subtypes to predict pCR in the breast (pCRB; in situ allowed) following 18 weeks of neoadjuvant lapatinib and trastuzumab...6 year DFS and DDFS were 91.7% and 93.7%, respectively....Of the 12 patients who did not receive CT, 6 (50%) pts achieved a pCRB, and no relapse events were observed....Despite the small sample size, PAMELA opens the door to study dual HER2 blockade without chemotherapy in selected pts.

EPHOS-B aimed to determine whether perioperative anti-HER2 therapy inhibited proliferation and/or increased apoptosis in HER2-positive breast cancer....Six patients achieved complete pathologic response (pCR, RCB0) and 13 RCB1, all but two in the combination group.

...patients with human epidermal growth factor receptor 2-positive, stage II-IIIA breast cancer….at 9-year median follow-up, a trend towards RFS improvement with lapatinib-trastuzumab over trastuzumab was observed...Cher-LOB trial survival analysis confirmed the prognostic role of pCR and TILs and showed a signal for a better outcome with lapatinib-trastuzumab over trastuzumab.

Overall 6 studies with 843 HER-2 positive breast cancer patients (442 HER-2 amplified disease, 399 luminal B disease) were included in this systematic review and meta-analysis...Combination of the two (trastuzumab plus lapatinib) was associated with increased survival advantage compared to each agent alone (0.55 [0.32, 0.92], p = 0.02)....Lapatinib has shown intracranial activity and yielded better survival for HER-2+ BC patients with BMs. SRS in combination with ever use of lapatinib had better local control and were associated with better survival. Radiation necrosis risk was reduced with the use of lapatinib.

ALTTO was a large phase III study evaluating the addition of lapatinib (L) to T for early-stage HER2+ BC pts…As such, for pts under concomitant CT (N=1235), 96 DFS events occurred for 7y DFS rates of 84% (95% CI [77-90]), 91% (86-94), 93% (89-96), and 89% (83-93) in L, T, T+L, and T⟶L, respectively (p=0.038).

Key inclusion criteria were stage IV HER2 positive breast cancer...12 patients (85.7%) had an objective response including 6 CR and 2 PR….12 patients (85.7%) had an objective response including 6 CR and 2 PR.

In the overall cohort, the median disease-free survival (DFS) was 19.0 months; the median progression-free survival (PFS), 6.3 months; and median overall survival (OS), 88.0 months, with 32.2% of patients alive at 5 years. In the second line setting, the median PFS among trastuzumab, lapatinib, and trastuzumab plus lapatinib were 4.2 months, 5.2 months, and 7.3 months, respectively (P = 0.004). Our findings suggest that patients would benefit more from trastuzumab plus lapatinib than from lapatinib or trastuzumab alone for second line treatment in the advanced stages of the disease.

Chinese patients with HER2-positive relapsed or metastatic breast cancer previously treated with taxanes, anthracyclines, and/or trastuzumab were assigned (1:1) to receive 400 mg pyrotinib or lapatinib 1,250 mg orally once per day for 21-day cycles in combination with capecitabine (1,000 mg/m2 orally twice per day on days 1 to 14). The overall response rate was 78.5% (95% CI, 68.5% to 88.5%) with pyrotinib and 57.1% (95% CI, 44.9% to 69.4%) with lapatinib (treatment difference, 21.3%; 95% CI, 4.0% to 38.7%; P = .01).