Palbociclib plus letrozole versus weekly paclitaxel, both in combination with trastuzumab plus pertuzumab, as neoadjuvant treatment for patients with HR-positive/HER2-positive early breast cancer: primary results from the randomized phase II TOUCH trial (IBCSG 55-17).

Cyclin-dependent kinase 4 and 6 inhibitors with endocrine and anti-HER2 therapy have shown a potential for chemotherapy omission in this context.

与内分泌和抗HER2治疗联合使用的细胞周期依赖性激酶4和6抑制剂在这种情况下显示出避免化疗的潜力。

patients_and_methods

TOUCH is an international, open-label, phase II trial for postmenopausal patients with cT >1 cm, cN0 or cN1, HR-positive/HER2-positive BC, randomly assigned to 16 weeks of neoadjuvant weekly paclitaxel or palbociclib and letrozole, both with trastuzumab + pertuzumab (HP).

TOUCH 是一项国际性的、开放标签的、针对绝经后患者进行的II期临床试验，这些患者的临床分期为 cT>1 cm，cN0 或 cN1，激素受体阳性/HER2阳性乳腺癌，随机分配接受16周的每周新辅助化疗帕妥珠单抗或帕博西利和来曲唑，两者均联合使用曲妥珠单抗加帕妥珠单抗（HP）治疗。

The primary objective investigated the interaction between a gene signature of E2F pathway activity (RBsig) and pCR (ypT0N0 or ypTisN0), hypothesizing higher pCR for RBsig-high tumors in the paclitaxel + HP group and for RBsig-low tumors in the palbociclib + letrozole + HP group.

主要研究目标是研究E2F通路活性（RBsig）基因签名与病理完全缓解（pCR）（ypT0N0 或 ypTisN0）之间的相互作用，假设在帕妥珠单抗 + HP 组中，RBsig高表达的肿瘤会有更高的pCR率，而在帕博西利 + 来曲唑 + HP 组中，RBsig低表达的肿瘤会有更高的pCR率。

RBsig was assessed by RNA-sequencing from pre-treatment biopsies; intrinsic subtypes were estimated by absolute intrinsic molecular subtyping Treatment-by-biomarker interaction was estimated using logistic regression in 115 assessable patients.

RBsig通过RNA测序从治疗前活检中评估；通过绝对内在分子分型估计内在亚型。在115名可评估患者中使用逻辑回归估计治疗与生物标志物的相互作用。

Results

A total of 147 patients were randomly assigned (74 paclitaxel + HP, 73 palbociclib + letrozole + HP) and 145 constituted the treated population, with a median age of 69 years (interquartile range 63-73 years).

共有147名患者被随机分配（74名接受紫杉醇+HP治疗，73名接受帕博西利+来曲唑+HP治疗），145名患者构成治疗人群，中位年龄为69岁（四分位数间距63-73岁）。

More patients completed palbociclib versus paclitaxel (94.4% versus 79.5%).

更多患者完成了帕博西利治疗而非紫杉醇治疗（94.4%对比79.5%）。

The most frequent grade 3-4 adverse events were neutropenia and diarrhea (6.9% versus 43.1% and 11% versus 8.3% in the paclitaxel + HP versus the palbociclib + letrozole + HP groups, respectively).

最常见的3-4级不良事件是中性粒细胞减少症和腹泻（紫杉醇+HP组与帕博西利+来曲唑+HP组相比，分别为6.9%对比43.1%和11%对比8.3%）。

The pCR rate was 32.9% [95% confidence interval(CI) 22.3% to 44.9%] in the paclitaxel + HP group and 33.3% (95% CI 22.7% to 45.4%) in the palbociclib + letrozole + HP group.

在紫杉醇+HP组中，病理完全缓解（pCR）率为32.9%（95%置信区间[CI] 22.3%至44.9%），而在帕博西利+来曲唑+HP组中，pCR率为33.3%（95% CI 22.7%至45.4%）。

No significant treatment-by-RBsig interaction was observed (P = 0.18): pCR in RBsig high versus low was 31.3% (95% CI 16.1% to 50.0%) versus 42.3% (95% CI 23.4% to 63.1%) in the paclitaxel + HP group, and 38.5% (95% CI 20.2% to 59.4%) versus 25.8% (95% CI 11.9% to 44.6%) in the palbociclib group. pCR was higher in non-luminal versus luminal subtypes (45.5% versus 18.4%), with no interaction with treatment.

未观察到治疗与RBsig的显著相互作用（P=0.18）：在紫杉醇+HP组中，RBsig高表达与低表达的pCR率分别为31.3%（95% CI 16.1%至50.0%）和42.3%（95% CI 23.4%至63.1%），而在帕博西利组中，分别为38.5%（95% CI 20.2%至59.4%）和25.8%（95% CI 11.9%至44.6%）。非腔内型与腔内型亚型的pCR率较高（45.5%对比18.4%），与治疗无相互作用。

Conclusions

Although the primary hypothesis was not supported, TOUCH shows that dual anti-HER2 blockade with a chemotherapy-free backbone of palbociclib + letrozole yields pCR rates similar to paclitaxel, representing an attractive alternative treatment strategy.

尽管主要假设未得到支持，TOUCH研究显示，使用化疗药物帕博西利和来曲唑的无化疗双靶向HER2阻断方案可获得与紫杉醇相似的病理完全缓解（pCR）率，这代表了一种有吸引力的替代治疗策略。