First-Line Treatment with Bevacizumab and Paclitaxel Prolongs Progression-Free Survival in Metastatic Breast Cancer

1010 Background: Docetaxel has become a standard in management of metastatic breast cancer (MBC) patients (pts). However, there is no validated clinical or biological marker allowing to predict which pts are most likely to benefit from it. We evaluated the ability of Surface enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF MS) to identify serum proteins that could predict for docetaxel activity. Methods: We prospectively collected pretreatment serum of 81 HER2- MBC pts receiving docetaxel as first-line treatment. Serum samples were denatured, and then incubated in triplicates with three different ProteinChip arrays (Ciphergen): H50, IMAC30-Cu and CM10. Arrays were analysed using a PBSIIc ProteinChip reader (Ciphergen). Results: Pt characteristics were the following: median age, 53 ys (34 -71); Hormonal Receptivity (HR) (yes/no/na, %) 76/15/9; Disease-free interval (DFI) (≤24 months/>24 months, %) 42/58; visceral disease (yes/no, %) 35/65; metastatic sites (<3/≥3,%) 85/15; Median follow-up, 19.8 months (95%CI, 16.1–21.9); Median Progression-free survival (PFS), 12.9 months (95%CI, 8.8–18). Overall, 521 protein peaks were resolved. Univariate Cox proportional hazards regression identified 20 proteins significantly associated to PFS (P < 0.01). A stepwise procedure using the Akaike information criterion was applied to build a Cox model with 7 protein peaks allowing to calculate a risk index for each pt. Using the risk index median value as cut-off, high-risk and low-risk populations with dramatic differences in PFS were identified (2-year PFS of 0% and 54.6%, p = 1.45 10–8). Validation methods included leave-one-out cross validation and iterative resampling. In a multivariate Cox regression including conventional prognostic factors (HR, DFI, visceral metastasis) and serum protein risk index, the latter retained the strongest independent prognostic significance for PFS. Identification of proteins with differential expression according to clinical outcome is ongoing. Conclusions: Serum proteomic profiling may help select MBC Pts who will benefit from treatment with docetaxel. Validation on an independent dataset is planned. No significant financial relationships to disclose.

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Efficacy of pertuzumab in combination with trastuzumab and a taxane in first-line treatment for metastatic breast cancer (MBC): A multicenter, retrospective, observational study.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e12504 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e12504-e12504 ◽

Cited By ~ 1

Author(s):

Teresa Gamucci ◽

Lucia Mentuccia ◽

Isabella Sperduti ◽

Alain Gelibter ◽

Loretta D'Onofrio ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Observational Study ◽

Real World ◽

Metastatic Breast ◽

Progression Free Survival ◽

Rank Test ◽

Line Treatment ◽

First Line ◽

First Line Treatment

e12504 Background: Pertuzumab (P) , Trastuzumab (T) and Docetaxel (D) is standard first-line treatment in patients (pts) with HER2 + metastatic breast cancer (MBC). This multicenter retrospetive observational study was performed to evaluate the activity of P and T in combination with D or Paclitaxel (Tx) in real world HER2 + MBC pts. Methods: We identified HER2 + MBC pts treated with P, T and D or Ptx optionally followed by P, T and endocrine therapy (ET) maintenance in hormone positive (HR+) BC, in 17 Italian cancer centres between 09/2012 and 08/2016. Overall Survival (OS) and Progression Free Survival (PFS) were calculated by the Kaplan-Meier product-limit method. Log-rank test was used to assess differences between subgroups. Results: 191 pts were included in our analysis. Pts characteristics: median age 54 years (range 29-80); PS 0 in 127 (67%) pts and PS 1 in 54 (28%); 107 (56%) had visceral metastases (mts), 23 (12%) only bone mts and 28 (15%) brain mts, 130 (68%) were ER/PgR +. 76 pts (40%) were metastatic at diagnosis; 148 (78) were treated with D while 43 (22%) with Tx. The ORR was 78% (CI 95% 72-84), RC 18% and RP 60%, only 10 (5%) had PD. To date, of the 54 pts treated with ET maintenance, 26% had a further improvement of response (7 pts had RC). At median follow-up of 17 months (mo) (range 6- 52), median PFS was 20 mo (95% CI 14-26) and median OS at 2 years was 80%. No differences in PFS were found for age (p = 0.92), PS (p = 0.18), receptor status (p = 0.57), visceral mts (p = 0.54) and chemotherapy (cht) type (p = 0.47), whereas number of mts site (1 vs > 1) affected PFS (28 vs 16 mo, p = 0.002). Moreover median PFS in naïve pts and in pts pretreated with only cht was 28 mo (95% CI, 20-36) and 27 mo (95% CI, 16-38) respectively, whereas in pts pretreated with T it was 12 mo (95% CI 16-38 p 0.002). In HR+ pts ET maintenance together with P and T had an impact on PFS (28 vs 15 mo, p = 0.01). Conclusions: Our analysis confirms, in real world HER2 MBC pts, the efficacy of P, T and a taxane combination in first line treatment; in this population PFS was shorter in pts pretreated with T. ET maintenance in association with P and T in HR+ pts improved PFS. Data collection is ongoing and update results will be presented.

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