Celgene Corporation
Dec 7, 2017
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Long-Term Efficacy Data from the Phase III GeparSepto Study in High Risk Early Breast Cancer Patients Treated with ABRAXANE® Vs. Solvent-Based Paclitaxel to Be Reported

-- Phase III Secondary Endpoint Results Demonstrate A Significantly Higher Disease-free Survival Rate following ABRAXANE as Investigational Therapy in Neoadjuvant Breast Cancer --

NEU-ISENBURG, Germany & SUMMIT, N.J.--(BUSINESS WIRE)-- The German Breast Group (GBG) and Celgene Corporation (NASDAQ:CELG) today announced long-term invasive disease-free survival results from the GeparSepto clinical trial comparing the investigational use of ABRAXANE® (paclitaxel albumin-bound particles for injectable suspension) to paclitaxel in early high-risk breast cancer patients at the 2017 San Antonio Breast Cancer Symposium (SABCS). The results from the 1,206 patient study found that ABRAXANE demonstrated a significantly higher disease-free survival rate, a secondary efficacy endpoint, in high risk early breast cancer patients when compared to conventional solvent-based paclitaxel.

In this large Phase III study, of which disease-free survival was a secondary endpoint, the investigational use of ABRAXANE (N=600) was compared to conventional solvent-based paclitaxel (N=606) followed by epirubicin/cyclophosphamide in both arms given all before surgery. The study found a significantly higher disease-free survival (DFS) rate in patients receiving ABRAXANE compared to those receiving paclitaxel as part of a neoadjuvant treatment regimen [HR=0.69, 95% CI (0.54-0.89); p=0.0044]). The rates of DFS were 87.1% vs. 80.7% at 3 years and 83.5% vs. 76.2% at 4 years, respectively. A treatment effect was observed in the predefined subset of patients with triple negative tumors and hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) tumors. Patients with triple negative breast cancer (n=276) had DFS rates of 83.1% vs. 73.4% at 3 years, and 78.7% vs. 68.6% at 4 years. DFS was not significantly different in the TNBC subgroup [HR=0.66, 95% CI (0.42-1.04), p=0.0694]. HR+/HER2- patients had DFS rates of 86.3% vs. 78.6% at 3 years and 80.8% vs. 72.8% at 4 years [HR=0.71, 95% CI (0.49-1.02); p=0.0660]. Another secondary endpoint measure evaluated in the study was overall survival (OS). No difference in OS was observed, however the OS findings are not yet mature.

"These long-term findings show that weekly nab-paclitaxel followed by epirubicin/cyclophosphamide helped to significantly delay the progression of disease compared to solvent-based paclitaxel followed by epirubicin/cyclophosphamide in early high-risk breast cancer patients," stated Sibylle Loibl, Chair of GBG. "These findings are consistent with our previous findings and are very exciting, as they help us evaluate another potential treatment option for this high-risk patient group."

The primary endpoint of GeparSepto was pCR (pathological complete response) which has been reported previously and found a statistically significant and clinically meaningful 9% absolute improvement from 29% to 38% (p= < 0.001) when neoadjuvant (preoperative) chemotherapy was started with ABRAXANE instead of conventional solvent-based paclitaxel followed by epirubicin/cyclophosphamide given prior to surgery.

The most common adverse events ( > 30%) that were previously reported included anemia, alopecia, peripheral sensory neuropathy neutropenia, leukopenia, fatigue, lymphopenia, increased alanine aminotransferase, increased aspartate aminotransferase, headache, nausea, mucositis/stomatitis/ esophagitis, diarrhea, infection, arthralgia, epistaxis, skin rash maculopapular, and myalgia.

Follow-up data regarding long-term neurotoxicity and quality of life will be collected during the study follow-up period. These results will be forthcoming in future analyses.

"These latest results are very encouraging, illustrating that an ABRAXANE-containing investigational regimen may have activity in high-risk breast cancer patients in the neoadjuvant setting," said Nadim Ahmed, President, Hematology and Oncology for Celgene. "The long-term outcomes from this study offer researchers additional insight into how to potentially treat patients more effectively at an earlier stage of the disease."

ABRAXANE is not approved for neoadjuvant treatment of breast cancer, or for the treatment regimens studied in GeparSepto in any country. See label excerpts below for more information.

About GeparSepto

GeparSepto is a phase III clinical trial evaluating the safety and efficacy of the investigational use of a weekly treatment regimen of nab-paclitaxel compared to a solvent-based paclitaxel, both followed by epirubicin/cyclophosphamide given all before surgery to treat high-risk early breast cancer.

The trial evaluated 1,206 patients with high risk early breast cancer. Patients received either nab-paclitaxel 150 mg/m2 or paclitaxel 80 mg/m2 weekly for 12 weeks followed by epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2 every 3 weeks for 12 weeks. HER2 positive patients also received trastuzumab 8 (6) mg/kg and pertuzumab 840 (420) mg every 3 weeks during neoadjuvant treatment. The nab-paclitaxel dose was reduced to 125 mg/m2 after recruitment of 464 patients because of the evaluation of an interim safety analysis. The median age in each treatment arm was 49 (nab-paclitaxel) and 48 (paclitaxel) years. The primary endpoint of the trial was pathological complete response (pCR). Secondary endpoints evaluated in the study included invasive disease-free survival (DFS), distant disease-free survival (DDFS) and overall survival (OS).

Grade 3 and 4 neutropenia occurred in 23% and 38% of patients, respectively, in the nab-paclitaxel arm compared to 25% and 36% in the solvent-based paclitaxel arm. Peripheral sensory neuropathy was more common with nab-paclitaxel (8% for the 125 mg/m2 dose and 15% for the 150 mg/m2 dose) compared with solvent-based paclitaxel 80 mg/m2. Taxane discontinuation due to an adverse event occurred in 16% of patients on nab-paclitaxel and 6% on solvent-based paclitaxel.

Overall, 23% of patients were noted to have at least one serious adverse event based on the study drug received (26% in the nab-paclitaxel group and 21% in the solvent-based paclitaxel group [p=0.057]). There were three deaths (during epirubicin plus cyclophosphamide treatment) in the nab-paclitaxel group due to sepsis, diarrhea, and an accident unrelated to the trial, compared to one death in the solvent-based paclitaxel group (during paclitaxel treatment) due to cardiac failure.

GeparSepto is the largest randomized Phase III study ever completed with ABRAXANE and the first one completed in high risk early breast cancer. Celgene provided funding support for the GeparSepto trial.

ABOUT ABRAXANE

ABRAXANE® for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) is indicated for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated.

Important Safety Information

WARNING - NEUTROPENIA

CONTRADINDICATIONS

Neutrophil Counts

Hypersensitivity

WARNINGS AND PRECAUTIONS

Hematologic Effects

Nervous System

Hypersensitivity

Hepatic Impairment

Albumin (Human)

Use in Pregnancy: Pregnancy Category D

Use in Men

ADVERSE REACTIONS

Randomized Metastatic Breast Cancer (MBC) Study

Postmarketing Experience With ABRAXANE and Other Paclitaxel Formulations

DRUG INTERACTIONS

USE IN SPECIFIC POPULATIONS

Nursing Mothers

Pediatric

Geriatric

Renal Impairment

DOSAGE AND ADMINISTRATION

Please see full Prescribing Information, including Boxed WARNING.

About the German Breast Group

GBG is a large independent academic network of over 500 study centers in Germany with the world- wide largest experience in conducting neoadjuvant breast cancer trials. Since 1998, with joined forces from AGO-B, over 10.000 patients participated in the neoadjuvant "Gepardo" trial series. GBG has recruited at totality of over 35.000 patients to trials in breast cancer of all indications. Reports on these trials were previously published in the New England Journal of Medicine, The Lancet Oncology, the Journal of Clinical Oncology and the Journal of the National Cancer Institute (for more information go to www.germanbreastgroup.de). The GBG Research Institute received unrestricted grants and the provision of medication from Celgene and Roche for the conduct of the GeparSepto study. ABRAXANE is approved in the US and Europe for patients with metastatic breast cancer.

About Celgene

Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through next-generation solutions in protein homeostasis, immuno-oncology, epigenetics, immunology and neuro-inflammation. For more information, please visit www.celgene.com. Follow Celgene on Social Media: @Celgene, Pinterest, LinkedIn, FaceBook and YouTube.

Forward-Looking Statements

This press release contains forward-looking statements, which are generally statements that are not historical facts. Forward-looking statements can be identified by the words "expects," "anticipates," "believes," "intends," "estimates," "plans," "will," "outlook" and similar expressions. Forward-looking statements are based on management's current plans, estimates, assumptions and projections, and speak only as of the date they are made. We undertake no obligation to update any forward-looking statement in light of new information or future events, except as otherwise required by law. Forward-looking statements involve inherent risks and uncertainties, most of which are difficult to predict and are generally beyond our control. Actual results or outcomes may differ materially from those implied by the forward-looking statements as a result of the impact of a number of factors, many of which are discussed in more detail in our Annual Report on Form 10-K and our other reports filed with the Securities and Exchange Commission.

Hyperlinks are provided as a convenience and for informational purposes only. Neither Celgene nor the German Breast Group bears responsibility for the security or content of external websites or websites outside of their respective control.

For the German Breast Group:
Mara Eichenaub
Mara.Eichenlaub@gbg.de
or
For Celgene:
Investors:
908-673-9628
investors@celgene.com
or
Media:
908-673-2275
media@celgene.com

Source: The German Breast Group and Celgene Corporation

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