Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.
Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.
Clin Cancer Res. 2020 Feb 15;26(4):821-827. doi: 10.1158/1078-0432.CCR-19-0851. Epub 2019 Oct 29.
Prior neoadjuvant trials with 12 weeks of dual anti-HER2 therapy without chemotherapy demonstrated a meaningful pathologic complete response (pCR) in patients with HER2-positive breast cancer. In this trial, we sought to determine whether longer treatment would increase the rate of pCR.
TBCRC023 (NCT00999804) is a randomized phase II trial combining a Simon phase II design in the experimental arm with a pick-the-winner design, not powered for direct comparison. Women with HER2-positive breast tumors measuring ≥2 cm (median = 5 cm) were randomized in a 1:2 ratio to 12 versus 24 weeks of lapatinib and trastuzumab. Letrozole (along with ovarian suppression if premenopausal) was administered in patients whose tumors were also estrogen receptor (ER) positive. All evaluable patients were assessed for in-breast pCR.
Ninety-seven patients were enrolled (33 in 12-week arm and 64 in 24-week arm), of whom 94 were evaluable. Median age was 51 years, and 55% were postmenopausal. Median tumor size was 5 cm, and 65% were ER-positive. The rate of pCR in the 24-week arm was 28% and numerically superior to the 12-week arm (12%). This was driven by increased pCR in the ER-positive subgroup (33% vs. 9%). Study treatment was well tolerated, with grade 1-2 diarrhea and acneiform rash being the most common toxicities.
Treatment with dual anti-HER2 therapy for 24 weeks led to a numeric increase in pCR rate in women with HER2-positive breast cancer, without using chemotherapy. If validated, this approach may help identify patients who may benefit from deescalation of therapy.
先前的 12 周双抗 HER2 治疗新辅助试验显示，HER2 阳性乳腺癌患者的病理性完全缓解（pCR）有显著意义。在这项试验中，我们试图确定更长时间的治疗是否会提高 pCR 率。
TBCRC023（NCT00999804）是一项随机的 2 期试验，在实验组结合 Simon 2 期设计和胜者选择设计，未进行直接比较的功效设计。HER2 阳性肿瘤≥2cm（中位数=5cm）的女性患者按照 1:2 的比例随机分为 12 周组和 24 周组，分别接受拉帕替尼和曲妥珠单抗治疗。如果肿瘤也是雌激素受体（ER）阳性，患者还接受来曲唑治疗（与卵巢抑制联合应用，如果是绝经前）。所有可评估的患者都进行了乳房内 pCR 评估。
共纳入 97 例患者（12 周组 33 例，24 周组 64 例），其中 94 例可评估。中位年龄为 51 岁，55%为绝经后。中位肿瘤大小为 5cm，65%为 ER 阳性。24 周组的 pCR 率为 28%，数值上优于 12 周组（12%）。这主要是由于 ER 阳性亚组的 pCR 增加（33% vs. 9%）。研究治疗耐受性良好，最常见的毒性是 1-2 级腹泻和痤疮样皮疹。
在 HER2 阳性乳腺癌患者中，用双抗 HER2 治疗 24 周可导致 pCR 率的数值增加，而无需使用化疗。如果得到验证，这种方法可能有助于识别可能从治疗降级中受益的患者。
