Neoadjuvant palbociclib on ER+ breast cancer (N007): clinical response and EndoPredict’s value

Abstract

The purpose of the study was to test the efficacy of neoadjuvant palbociclib therapy and to evaluate its impact on cell cycle arrest and changes in EndoPredict (EP) scores before and after treatment. Postmenopausal women with histologically proven ER+ve, HER2−ve invasive breast cancer, 2 cm or greater, were enrolled in an open-label, single-arm study. Twenty eligible patients were given letrozole 2.5 mg per day together with palbociclib 125 mg per day for 3 out of 4 weeks in repeated cycles for 16 weeks (4 cycles) before surgery. The primary end points were clinical response rates (cRR) and preoperative endocrine prognostic index (PEPI). The secondary end points were pathologic response and gene expression testing with EP test on collected tumor samples. The following results were obtained. 17 patients showed a clinical response of 50% or more, including 8 complete responses and 9 partial responses. There was significant reduction in area (P < 0.0001) and volume (P = 0.017) of the cancer. Pathologic complete response (pCR) was achieved in one patient; all cancers were downgraded after treatment. Ki67 (P = 0.044) and EP scores (P < 0.0001) were significantly reduced after treatment. Analysis of the relative gene expression levels showed that all proliferative genes, IL6ST and RBBP8 were decreased after palbociclib treatment. 6 patients with intermediate and three patients with high PEPI risk scores were found to have low EPclin scores. All patients with high PEPI relapse risk score had high EPclin score. In conclusion, effective clinical response was demonstrated by neoadjuvant letrozole in combination with palbociclib. Compared with PEPI, EPclin might be a better parameter to estimate prognosis after neoadjuvant therapy.

Inhibitors targeting CDK4/6, PARP and PI3K in breast cancer: a review

“… 28 Another neoadjuvant phase II trial on ER-positive, HER2-negative invasive breast cancer patients ( n = 20) reported that 17 (85%) patients showed a clinical tumor response while 8 (40%) and 9 (45%) patients had complete response (CR) and partial response (PR), respectively. 29 Analysis of the relative gene expression levels showed that all proliferative genes’ ( IL6ST, RBBP8 and MKI67 ) expression were decreased after the treatment. 29 …”

“… 29 Analysis of the relative gene expression levels showed that all proliferative genes’ ( IL6ST, RBBP8 and MKI67 ) expression were decreased after the treatment. 29 …”

“… 28 Furthermore, Chow and colleagues (phase II trial) reported that >50% of the patients developed febrile neutropenia with grade 3/4 neutropenia. 29 DeMichele and colleagues 19 proposed that palbociclib’s mechanism of myelosuppression may differ from that of traditional drugs where grade 3/4 neutropenia that occurred was largely uncomplicated, with one incident of fever and sepsis occurring in a neutropenic patient.…”

<p>Strategies for Increasing the Effectiveness of Aromatase Inhibitors in Locally Advanced Breast Cancer: An Evidence-Based Review on Current Options</p>

“…More than half of patients developed a G3/G4 neutropenia that required a reduction of dose or discontinuation of the therapy. 43 The results of the PALLET study were recently published. A total of 307 postmenopausal women with HR +/HER2-(>2 cm in size) tumors were randomized to receive letrozole alone for 14 weeks (arm A), letrozole single-agent for 2 weeks followed by the addition of palbociclib for 12 weeks (arm B), palbociclib singleagent for 2 weeks followed by the addition of letrozole for 12 weeks (arm C) or letrozole plus palbociclib for 14 weeks (arm D).…”

SABCS 2017 pathology: from bench to bedside

“…Although numerous findings on multigenomic assays had been presented at past symposia, this year the only presentation in a plenary session reported about the use of the EndoPredict multigenomic test. Peter Dubsky presented the analysis of the ABCSG 34 neoadjuvant trial on the efficacy of the EndoPredict multigenomic assay to predict response to neoadjuvant endocrine and chemotherapy [ 9 , 10 ]. This analysis included all patients with estrogen-receptor (ER) positive tumors who received neoadjuvant chemo- or endocrine therapy within the ABCSG 34 trial.…”