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

Louis W C Chow, Satoshi Morita, Christopher Y C Chow, Wai-Kuen Ng, Masakazu Toi, Louis W C Chow, Satoshi Morita, Christopher Y C Chow, Wai-Kuen Ng, Masakazu Toi

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.

Keywords: EndoPredict; breast cancer; letrozole; neoadjuvant; palbociclib.

© 2018 The authors.

Figures

Figure 1
Figure 1
The volume of the cancer on three-dimensional measurement before and after treatment with neoadjuvant letrozole in combination with palbociclib. Each line represents the data for individual patient.
Figure 2
Figure 2
(A) Overall change in Ki67 before and after treatment with neoadjuvant letrozole in combination with palbociclib. Each line represents the data for individual patient. Ki67 >15% was considered as high proliferation fraction. (B) Change in Ki67 before treatment, on day 15 and after treatment with neoadjuvant letrozole in combination with palbociclib. Each line represents the data for individual patient. Ki67 >15% was considered as high proliferation fraction.
Figure 3
Figure 3
Change in relative gene expression level (dCt) of gene of interest. Each level represents the data for each individual patient.
Figure 4
Figure 4
Change in EP score before and after treatment with neoadjuvant letrozole in combination with palbociclib. Each line represents the data for individual patient. EP score

Figure 5

Distribution of PEPI scores. A…

Figure 5

Distribution of PEPI scores. A PEPI score of 0 predicts a low risk…

Figure 5
Distribution of PEPI scores. A PEPI score of 0 predicts a low risk of recurrence; a score of 1–3 predicts an intermediate risk of recurrence; a score of 4 or higher predicts a high risk of recurrence. BCSS, breast cancer-specific survival; PEPI, preoperative endocrine prognostic index; RFS, relapse-free survival.

Figure 6

Distribution of EPclin scores. EPclin…

Figure 6

Distribution of EPclin scores. EPclin score

Figure 6
Distribution of EPclin scores. EPclin score

Figure 7

Neutropenia during the course of…

Figure 7

Neutropenia during the course of treatment. AE, adverse events.

Figure 7
Neutropenia during the course of treatment. AE, adverse events.
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References
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Figure 5
Figure 5
Distribution of PEPI scores. A PEPI score of 0 predicts a low risk of recurrence; a score of 1–3 predicts an intermediate risk of recurrence; a score of 4 or higher predicts a high risk of recurrence. BCSS, breast cancer-specific survival; PEPI, preoperative endocrine prognostic index; RFS, relapse-free survival.
Figure 6
Figure 6
Distribution of EPclin scores. EPclin score

Figure 7

Neutropenia during the course of…

Figure 7

Neutropenia during the course of treatment. AE, adverse events.

Figure 7
Neutropenia during the course of treatment. AE, adverse events.
All figures (7)
Figure 7
Figure 7
Neutropenia during the course of treatment. AE, adverse events.

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