A pilot feasibility study to evaluate the efficacy of lapatinib in eliminating HER2-positive tumor cells circulating in peripheral blood of women with metastatic breast cancer.

Abstract

e22105 Background: EGFR and HER2 are expressed on CTCs from pts with breast cancer (BC). In this study we aimed to evaluate the efficacy of lapatinib, a dual EGFR and HER2 TK inhibitor, to eliminate HER2+ CTCs in metastatic BC. Methods: Pts with metastatic disease and HER2+ CTCs detected after disease stabilization or response to prior therapy were eligible. Pts received lapatinib till disease or CTC progression, whichever occurred first. Cytospins of peripheral blood mononuclear cells (PBMCs) were double stained with HER2 or EGFR along with cytokeratin antibody; 106 PBMCs/pt were analyzed for each molecule. Results: Twenty-two pts were enrolled; median age was 62.5 yrs, 2 had HER2+ primary, 12 (54.5%) had visceral disease and 8 (36.4%) had received ≥3 lines. Treatment was discontinued in 1 pt before the end of the 1st cycle due to toxicity and 1 withdrew consent after 3 cycles. A total of 119 courses were administered [median 4.0 (range, 0.5-26.0)]; disease evaluation revealed SD in 11 pts and PD in 10. HER2+ CTC counts declined in 18 (85.7%) pts during treatment [median time to nadir 1 mo (range, 1 – 5)]. After the 1st cycle, HER2+ CTCs decreased in 14 (66.7%) pts, increased in 6 (28.6%) and remained stable in 1 (4.7%). At baseline, 3444 HER2+ CTCs were detected (median 130), whereas after the 1st and 2nd cycles, 2281 (median 1) and 989 (median 2), respectively, were identified. The difference between baseline and post-1st or post-2nd cycle CTC counts was significant for all pts and for patients with SD but not in progressing pts. EGFR expression on CTCs was evaluated at the baseline and the end of treatment sample; in 6 of 8 pts with CTCs detected at both time points, the % EGFR+ CTCs/pt increased from a mean of 29.72% to 71.52%. Moreover, the % ratio of EGFR+ among the total CTCs increased from 17.08% to 37.59%. Conclusions: Lapatinib is effective in decreasing HER2+ CTCs in pts with metastatic BC, irrespective of the HER2 status of the primary. EGFR+ CTCs increase during treatment implicating EGFR as a possible resistance mechanism. The above results suggest that tailoring therapy according to targets present on CTCs represents an effective therapeutic strategy in BC. Clinical trial information: NCT00694252.