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Background: In a phase III trial of women with HER2+ metastatic breast cancer (MBC) previously treated with trastuzumab, an anthracycline, and taxanes (EGF100151), lapatinib plus capecitabine (L + C) improved time to progression (TTP) versus capecitabine monotherapy (C-only). In a trial including HER2+ MBC patients who had received at least one prior course of trastuzumab and no more than one prior course of palliative chemotherapy (GBG 26/BIG 03-05), continued trastuzumab plus capecitabine (T + C) also improved TTP. Methods: An economic model using patient-level data from EGF100151 and published results of GBG 26/BIG 03-05 as well as other literature were used to evaluate the incremental cost per quality-adjusted life-year [QALY] gained with L + C versus C-only and versus T + C in women with HER2+ MBC previously treated with trastuzumab from the UK National Health Service (NHS) perspective. Results: Expected costs were £28,816 with L + C, £13,985 with C-only and £28,924 with T + C. Corresponding QALYs were 0.927, 0.737 and 0.896. In the base case, L + C was estimated to provide more QALYs at a lower cost compared with T + C; cost per QALY gained was £77,993 with L + C versus C-only. In pairwise probabilistic sensitivity analyses, the probability that L + C is preferred to C-only was 0.03 given a threshold of £30,000. The probability that L + C is preferred to T + C was 0.54 regardless of the threshold. Conclusions: When compared against capecitabine alone, the addition of lapatinib has a cost-effectiveness ratio exceeding the threshold normally used by NICE. Compared with T + C, L + C is dominant in the base case and approximately equally likely to be cost-effective in probabilistic sensitivity analyses over a wide range of threshold values. [ABSTRACT FROM AUTHOR]

Purpose: EPHOS-B aimed to determine whether perioperative anti-HER2 therapy inhibited proliferation and/or increased apoptosis in HER2-positive breast cancer., Patients and Methods: This randomized phase II, two-part, multicenter trial included newly diagnosed women with HER2-positive invasive breast cancer due to undergo surgery. Patients were randomized to: part 1 (1:2:2), no treatment (control), trastuzumab or lapatinib; part 2 (1:1:2) control, trastuzumab, or lapatinib and trastuzumab combination. Treatment was given for 11 days presurgery. Coprimary endpoints were change in Ki67 and apoptosis between baseline and surgery tumor samples (biologic response: ≥30% change). Central pathology review scored residual cancer burden (RCB). Relapse-free survival (RFS) explored long-term effects., Results: Between November 2010 and September 2015, 257 patients were randomized (part 1: control 22, trastuzumab 57, lapatinib 51; part 2: control 29, trastuzumab 32, combination 66). Ki67 response was evaluable for 223 patients: in part 1 Ki67 response occurred in 29/44 (66%) lapatinib versus 18/49 (37%) trastuzumab (P = 0.007) and 1/22 (5%) control (P < 0.0001); in part 2 in 36/49 (74%) combination versus 14/31 (45%) trastuzumab (P = 0.02) and 2/28 (7%) control (P < 0.0001). No significant increase in apoptosis after 11 days was seen in treatment groups. Six patients achieved complete pathologic response (pCR, RCB0) and 13 RCB1, all but two in the combination group. After 6 years median follow-up, 28 (11%) had recurrence and 19 (7%) died. No recurrences or deaths were observed among patients who achieved a pCR. Ki67% falls ≥50% associated with fewer recurrences (P = 0.002)., Conclusions: Early response after short duration anti-HER2 dual therapy identifies cancers dependent on the HER2 pathway providing a strategy for exploring risk-adapted individualized treatment de-escalation., (©2022 The Authors; Published by the American Association for Cancer Research.)

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=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.