On December 7, 2016 Abbott (NYSE: ABT) reported it has filed a complaint to terminate its proposed acquisition of Alere based on the substantial loss in Alere’s value following the merger agreement (Press release, Abbott, DEC 7, 2016, View Source [SID1234517000]).

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In the 10 months following the Jan. 30, 2016, signing of the agreement, Alere has suffered a series of damaging business developments, including the government eliminating the billing privileges of a substantial Alere division, the permanent recall of an important product platform, multiple new government subpoenas, including two new criminal subpoenas, and a five-month delay in filing its 10K coupled with admissions of internal control failures requiring restatement of its 2013-2015 financials.

"Alere is no longer the company Abbott agreed to buy 10 months ago," said Scott Stoffel, divisional vice president of external communications, Abbott. "These numerous negative developments are unprecedented and are not isolated incidents brought on by chance. We have attempted to secure details and information to assess these issues for months, and Alere has blocked every attempt. This damage to Alere’s business can only be the result of a systemic failure of internal controls, which combined with the lack of transparency, led us to filing this complaint."

Under terms of the merger agreement, Abbott may terminate the transaction if adverse events materially change Alere’s long-term prospects. Abbott filed its complaint seeking termination in the Delaware Court of Chancery, citing these events among others as material adverse events.

On December 7, 2016 Puma Biotechnology, Inc. (NYSE: PBYI), a biopharmaceutical company, reported that updated interim results from an ongoing Phase II clinical trial of Puma’s investigational drug PB272 (neratinib), given as monotherapy and in combination with the anticancer drug fulvestrant, were presented at the 2016 CTRC-AACR San Antonio Breast Cancer Symposium (SABCS) that is currently taking place in San Antonio, Texas (Press release, Puma Biotechnology, DEC 7, 2016, View Source [SID1234516992]). The presentation entitled "Neratinib plus fulvestrant for ERBB2 mutant, HER2 non-amplified, estrogen receptor-positive, metastatic breast cancer: Preliminary analysis from the Phase II SUMMIT trial" was presented as a poster discussion by Dr. David Hyman, Director, Developmental Therapeutics at Memorial Sloan Kettering Cancer Center.

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Interim results from this trial were previously presented at the 2015 SABCS and included patients who were treated with neratinib monotherapy for metastatic breast cancer and whose tumors have a HER2 mutation. The presentation also discussed that a bidirectional cross-talk between hormone receptor and HER2 signaling pathways could lead to endocrine resistance due to activated HER2 signaling and ER-mediated tumor proliferation as a potential resistance mechanism to sustained HER2 inhibition. Preclinical xenograft data has demonstrated that the combination of an anti-estrogen with neratinib results in enhanced anti-tumor activity in preclinical models of estrogen receptor positive/HER2-positive breast tumors. Based on this, the SUMMIT study was amended to allow for the combination of neratinib plus fulvestrant in eligible postmenopausal hormone receptor-positive breast cancer patients. The presentation at SABCS included an update on both the neratinib monotherapy cohort and the neratinib plus fulvestrant cohort.

In the study, patients with HER2 mutant metastatic breast cancer were enrolled and received 240 mg of neratinib daily either as monotherapy or in combination with fulvestrant. All patients received loperamide (16 mg per day initially) prophylactically for the first cycle of treatment in order to reduce the neratinib-related diarrhea. For the 25 patients in the group who received neratinib monotherapy, 23 patients (92%) had HER2-negative disease, 19 patients (76%) were hormone receptor positive (estrogen receptor or progesterone receptor positive), and patients had received a median of 4 prior lines of therapy in the metastatic setting (range 0-8 prior regimens) before entering the trial. For the 17 patients in the trial who received neratinib plus fulvestrant, 15 patients (88%) had HER2-negative disease, 17 patients (100%) were hormone receptor positive (estrogen receptor or progesterone receptor positive), and patients had received a median of 4 prior lines of therapy in the metastatic setting (range 1-7 prior regimens) before entering the trial.

The interim efficacy results from the trial showed that for the 24 efficacy evaluable patients in the neratinib monotherapy cohort, 8 patients (33.3%) experienced an objective response, which included 3 patients with a complete response and 5 patients with partial responses. At week 8, 8 patients (33.3%) achieved an objective response, with 2 patients achieving a complete response and 6 patients achieving a partial response The secondary endpoints of the trial included confirmed objective response (complete response or partial response), clinical benefit rate and progression free survival (PFS). The results of the trial showed that 6 patients (25%) had a confirmed objective response, 10 patients (41.7%) demonstrated clinical benefit and the median progression free survival was 3.5 months.

For the 12 efficacy evaluable patients in the neratinib plus fulvestrant cohort, 7 patients (58.3%) experienced an objective response, which included 2 patients with a complete response and 5 patients with partial responses. At week 8, 5 patients (41.7%) achieved an objective response, with 2 patients achieving a complete response and 3 patients achieving a partial response. The secondary endpoints of the trial included confirmed objective response (complete response or partial response), clinical benefit rate and progression free survival (PFS). The results of the trial showed that 3 patients (25%) had a confirmed objective response, 7 patients (58.3%) demonstrated clinical benefit and the median progression free survival was 3.7 months. The progression free survival data may not be mature in the neratinib plus fulvestrant cohort as 4 of the 12 efficacy evaluable patients are continuing to receive study treatment without disease progression and an additional 5 patients have not yet had an assessment for efficacy.

The interim safety results of the study showed that the most frequently observed adverse event was diarrhea. For the 25 patients enrolled in the neratinib monotherapy arm, 6 patients (24%) reported grade 3 diarrhea. The median duration of grade 3 diarrhea for the patients in the neratinib monotherapy cohort was 1 day. No patient in the neratinib monotherapy cohort has permanently discontinued neratinib due to diarrhea and 5 patients (20%) have temporarily discontinued neratinib due to diarrhea and then restarted after the diarrhea subsided. For the 17 patients enrolled in the neratinib plus fulvestrant cohort, 2 of 17 patients (12%) experienced grade 3 diarrhea. The median duration of grade 3 diarrhea was 1 day and typically occurred during the first cycle of treatment. No patient (0%) in the neratinib plus fulvestrant cohort permanently discontinued neratinib due to diarrhea and 2 patients (12%) temporarily discontinued neratinib due to diarrhea and then restarted after the diarrhea subsided.

Dr. David Hyman, Director, Developmental Therapeutics at Memorial Sloan Kettering Cancer Center and principal investigator of the trial, stated, "Neratinib showed promising signs of clinical activity both as a single agent and in the patients treated with the combination of neratinib plus fulvestrant in this preliminary analysis of pre-treated HER2 mutant breast cancer patients. The safety profile of the drug was manageable and the diarrhea was not treatment-limiting with appropriate prophylaxis and management. We look forward to completing the ongoing neratinib plus fulvestrant cohort and moving this combination forward into future clinical development."

Alan H. Auerbach, Chief Executive Officer and President of Puma Biotechnology, said, "We are very pleased with the preliminary activity seen with neratinib, both alone and in combination with fulvestrant in this cohort of patients with HER2 mutated breast cancer. We look forward to the completion of the trial and further development of the combination of neratinib and fulvestrant."

On December 7, 2016 Puma Biotechnology, Inc. (NYSE: PBYI), a biopharmaceutical company, reported that a biomarker analysis of the NSABP FB-7 Phase II clinical trial of Puma’s investigational drug PB272 (neratinib) was presented at the 2016 CTRC-AACR San Antonio Breast Cancer Symposium (SABCS) that is currently taking place in San Antonio, Texas (Press release, Puma Biotechnology, DEC 7, 2016, View Source [SID1234516991]). The presentation entitled "An exploratory correlative biomarker analysis of NSABP FB-7, a phase II randomized trial evaluating neoadjuvant therapy with weekly paclitaxel (P) plus neratinib (N) or trastuzumab (T) or neratinib and trastuzumab (N+T) followed by doxorubicin and cyclophosphamide (AC) with postoperative T in women with locally advanced HER2-positive breast cancer" was presented as a poster presentation. This trial was sponsored by the NSABP Foundation, Inc.

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The FB-7 trial is a randomized Phase II clinical trial for women with HER2-positive locally advanced stage IIB-IIIC invasive breast cancer. Patients were randomly assigned to receive trastuzumab (T) or neratinib (N) or the combination (T+N) with weekly paclitaxel (P) followed by standard doxorubicin and cyclophosphamide chemotherapy (AC) administered prior to surgery. 126 U.S., Canadian, and European patients were randomly assigned to Arm 1 (T+P followed by AC), Arm 2 (N+P followed by AC) or Arm 3 (T+N+P followed by AC). The primary endpoint of the trial was pathological complete response rate (pCR) in the breast and lymph nodes. The clinical safety and efficacy data from this trial was presented at the 2015 SABCS.

A key secondary endpoint of the FB-7 trial was to evaluate molecular and genetic markers for correlation with response. Pre-treatment core biopsy samples (n=59) and post treatment surgical samples (n=17) were obtained from a subset of patients treated in the FB-7 trial. pCR data were available for 51 patients from the biomarker cohort. After excluding low tumor content non-evaluable samples, correlative biomarker analysis was performed in 42 patients.

Expression levels and the activation status of EGFR/HER2 signaling proteins were investigated. The results of the phosphorylated HER2 (phosphoHER2) showed that median levels of phosphoHER2 were higher in the patients who achieved a pCR with neratinib (n=7) than in the patients who did not achieve a pCR who received either trastuzumab (n=8, p=0.07) or the combination of trastuzumab plus neratinib (n=4, p=0.035). There was not a significant difference in the median levels of phosphoHER2 in the patients who achieved a pCR with neratinib (n=7), trastuzumab (n=8, p=0.16) or the combination of trastuzumab plus neratinib (n=4, p=0.10).

The truncated form of HER2 known as p95HER2 was measured by the proprietary assay of Pierian Bioscience. p95HER2 represents a truncated form of the HER2 receptor that lacks the extracellular trastuzumab binding domain. It is believed to represent a mechanism of trastuzumab resistance. Median p95HER2 levels were higher in samples from patients who achieved a pCR with neratinib than in the patients who did not achieve a pCR who received either trastuzumab (p=0.027) or the combination of trastuzumab plus neratinib (p=0.009). There was not a significant difference in the median levels of p95HER2 in the patients who achieved a pCR with neratinib (n=7), trastuzumab (n=8, p=0.16) or the combination of trastuzumab plus neratinib (n=4, p=0.35).

The MammaPrint assay was performed on 59 samples to determine if there was any imbalance between arms. This assay is a genomic test that analyzes the activity of 70 genes and then calculates a recurrence score that is either low risk or high risk. The results of the MammaPrint showed that the patients in all three arms of the FB-7 trial were balanced with the median MammaPrint risk score being similar across arms. There were only three patients with a MammaPrint low score.

Dr. Samuel Jacobs, Emeritus Clinical Professor in the Department of Medicine, University of Pittsburgh School of Medicine, and the Director of Medical Affairs for the NSABP Foundation, Inc., said, "We are pleased to see the results of this exploratory biomarker analysis which suggests that activation of the HER pathway based on p95HER2 and phosphoHER2 may correlate with pCR to neratinib. Further biomarker analysis in additional datasets will be needed to determine which patients may derive the greatest benefit from neratinib."

Alan H. Auerbach, Chief Executive Officer and President of Puma Biotechnology, said, "We are pleased to complete this biomarker analysis of neratinib. Further results of the biomarker analysis should help us to determine the best path forward for neratinib in the neoadjuvant treatment of HER2-positive early stage breast cancer."

On December 7, 2016 PharmaCyte Biotech, Inc. (OTCQB:PMCB), a clinical stage biotechnology company focused on developing targeted treatments for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported the first article in a series of Q&A articles that will be conducted with some of the key team members of PharmaCyte’s planned clinical trial in locally advanced, inoperable pancreatic cancer (LAPC) (Press release, PharmaCyte Biotech, DEC 7, 2016, View Source [SID1234516987]). PharmaCyte’s first Q&A article is with Dr. Matthias Löhr of the famed Karolinska Institute in Stockholm, Sweden. Dr. Löhr was the Principal Investigator of the two earlier clinical trials using the Cell-in-a-Box technology in patients with advanced, inoperable pancreatic cancer.

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As PharmaCyte prepares to meet with the FDA in a Pre-IND meeting, what are your general thoughts of the Cell-in-a-Box plus low dose ifosfamide therapy for pancreatic cancer once again getting a chance to prove itself in patients?

Dr. Matthias Löhr: "I feel very confident and also happy to see the revival of this treatment concept. I consider Cell-in-a-Box as a platform technology. The previously raised concerns relating to the consistent reproducibility of the micro-capsules have been met by Austrianova in the meantime. Pancreatic cancer is a medical emergency (View Source) and is rising amongst the cancer related deaths, this year surpassing breast cancer to become number three, and by 2030 to become number two."

As the Principle Investigator of both of the earlier clinical trials, what are some of the highlights you recognized that you feel will once again be seen in PharmaCyte’s upcoming trial?

Dr. Matthias Löhr: "When we treated the first patients, they did not believe that they were receiving chemotherapy because there were NO side effects at all in the initial trial. That should be the case in PharmaCyte’s upcoming trial. Besides this very subjective impression, albeit repeated by all patients, we measured the quality of life, which was excellent – considering the dire disease. We will be measuring the quality of life in the upcoming trial as well. Further, we saw an effect not only on the primary tumor in the pancreas (where the capsules were injected) but also in some patients on the liver metastasis. This can only be explained by an immunological bystander effect that will likely be investigated in more depth in the upcoming clinical trial. Finally, in the first trial, certain patients’ tumors went from inoperable to operable. That is certainly a possibility in PharmaCyte’s trial, especially since we will be giving more than two courses of ifosfamide like we did in the first trial."

Why do you feel this new trial design can succeed?

Dr. Matthias Löhr: "The locally advanced pancreatic cancers are not sufficiently covered by guidelines – there is no standard of care, hence a highly unmet medical need. This refers particularly to those patients who received first line therapy, e.g. a very strong one (FOLFIRINOX) or combination of gemcitabine with Abraxane. AFTER this therapy, there is nothing left, especially an alternative with a low likelihood of side effects. The selection of these patients (group) is certainly to an advantage of the Cell-in-a-Box technology, which is mostly localized, may have a systemic (immunological) effect and has virtually no side effects. We consider this an ideal setting to the advantage of our patients in this upcoming clinical trial."

What are your thoughts on the benefits of using more rounds of the chemotherapy prodrug ifosfamide as PharmaCyte’s trial design calls for in this upcoming clinical trial?

Dr. Matthias Löhr: "This will definitively improve the outcome of the patients in this upcoming clinical trial. We couldn’t do this in the original trial(s) as we had no information on the stability of the capsules and activity of the cells converting the chemotherapy drug ifosfamide. This has changed now with the data developed from the first two trials. We will continue to administer ifosfamide until the patients receive no further benefit from our therapy. We can do that because we know the capsules are robust for at least two years and that the cells within them continue to convert ifosfamide during the life of the patient."

What are your thoughts on going head to head with gemcitabine?

Dr. Matthias Löhr: "No sweat. Gemcitabine is still the standard, due to the excellent tolerability of the drug and will be the drug used second line, especially after heavy protocols such as FOLFIRINOX or gemcitabine/ Abraxane. In this pretreated patient group, one has to use something with a very low profile on side effects. This is certainly the case with our Cell-in-A-Box."

What are your impressions of the team that surrounds the technology as PharmaCyte heads into its planned clinical trial?

Dr. Matthias Löhr: "PharmaCyte has the visionary capacity to see the potential of this platform technology, with pancreatic cancer being the first indication. They reached out to the original team, both those developing the technology and conducting the early phase clinical trials. Taking this knowledge on board is certainly the most important factor to ensure success. Further, with both Dr. Manuel Hidalgo and Dr. Daniel Von Hoff, two eminent oncologists with a lifetime track record in oncology and especially pancreatic cancer, the starting conditions could not be better."

On December 7, 2016 Celgene Corporation (NASDAQ:CELG) reported that the results of its randomized phase II tnAcity trial of ABRAXANE for injectable suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) will be presented at the 2016 San Antonio Breast Cancer Symposium (SABCS) December 6-10, 2016 (Press release, Celgene
, DEC 7, 2016, View Source [SID1234516986]). The trial found that an investigational weekly combination regimen of ABRAXANE + carboplatin had significantly longer progression-free survival (PFS) (7.4 months) compared to weekly regimens of either ABRAXANE + gemcitabine (5.4 months) or of carboplatin + gemcitabine (6.0 months) as first-line treatment of patients with metastatic triple-negative breast cancer (mTNBC).i

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The phase II trial randomized 191 women with mTNBC to receive one of three weekly regimens (dosed 2 out of 3 weeks): ABRAXANE + carboplatin, ABRAXANE + gemcitabine, or carboplatin + gemcitabine as first-line treatment. The study findings demonstrated that ABRAXANE + carboplatin resulted in significantly longer PFS (7.4 months) than combination regimens with ABRAXANE + gemcitabine (5.4 months; P=0.02, HR 0.60 (95% CI, 0.39-0.93)) or carboplatin + gemcitabine (6.0 months; P= 0.03, HR 0.61 (95% CI, 0.39-0.94)). tnAcity also found that those treated with the ABRAXANE + carboplatin regimen experienced a longer median treatment duration (25 weeks) than those treated with ABRAXANE + gemcitabine (18.1 weeks) or carboplatin + gemcitabine (20.1 weeks).i

The most common grade ≥3 treatment emergent adverse events (TEAEs) observed in the ABRAXANE + carboplatin, ABRAXANE + gemcitabine, and carboplatin + gemcitabine arms, respectively, during the study were mainly hematologic and included neutropenia (42%, 27%, 52%), anemia (13%, 12%, 27%), thrombocytopenia (9%, 7%, 28%), leukopenia (6%, 3%, 11%), febrile neutropenia (5%, 2%, 0%), peripheral neuropathy (5%, 7%, 2%) and fatigue (3%, 15%, 3%). A median of 8 treatment cycles were initiated for the ABRAXANE + carboplatin arm and 6 cycles for both the ABRAXANE + gemcitabine and carboplatin + gemcitabine arms. The percentage of patients that discontinued any study drug due to a TEAE was 45% for ABRAXANE + carboplatin and 25% for each of the other arms. The most common AEs leading to discontinuation of any study drug included thrombocytopenia, anemia, neutropenia and drug hypersensitivity.i

"Metastatic triple negative breast cancer is one of the most challenging types of cancers for treating physicians and patients alike, and there remains an important unmet need in these patients to find more effective treatment options," said Dr. Denise A. Yardley, Senior Investigator, Breast Cancer Research Program; Principal Investigator, Sarah Canon Research Institute. "These data add to the body of knowledge about ABRAXANE in metastatic triple negative breast cancer, a disease that requires additional research."

After taking into consideration the rapidly changing breast cancer treatment landscape, which has a significant focus on immuno-oncology treatments, Celgene had determined not to move forward with the phase III portion of tnAcity. The Company will instead focus its breast cancer research support on ABRAXANE/Immunotherapy combinations and remains committed to applying the findings of tnAcity to ongoing and future research of ABRAXANE in breast cancer for patients with high unmet needs.

"The findings of tnAcity are encouraging, illustrating that an ABRAXANE-containing regimen may have activity in a type of breast cancer with few viable treatments and these findings give researchers additional insight into how to treat metastatic triple negative breast cancer," said Michael Pehl, President, Hematology and Oncology for Celgene. "Celgene is committed to continuing to support research in breast cancer to identify regimens for patients with aggressive disease and in areas with limited treatment options."

ABRAXANE is not indicated for the first-line treatment of metastatic breast cancer, or for the treatment regimens studied in tnAcity.

ABOUT tnAcityi,ii

tnAcity is a phase II/III multicenter, open-label, randomized clinical trial conducted in 139 centers in 12 countries. The study evaluated the safety and efficacy of the investigational use of a weekly treatment regimen of ABRAXANE in combination with carboplatin or gemcitabine as a first-line treatment of women with metastatic triple negative breast cancer (mTNBC) compared to a gemcitabine + carboplatin regimen.ii

The phase II portion of the tnAcity trial evaluated 191 patients with metastatic triple negative breast cancer (mTNBC) who had received no prior systemic chemotherapy treatment for their mTNBC and had an ECOG performance status of 0 or 1. Patients were randomized to one of three treatment arms: ABRAXANE 125 mg/m2 + carboplatin AUC 2, ABRAXANE 125 mg/m2 + gemcitabine 1000 mg/m2, or carboplatin AUC 2 + gemcitabine 1000 mg/m2 dosed weekly on days 1 and 8 of a 21-day cycle. The median age in each treatment arm was 55 (ABRAXANE + carboplatin), 53 (ABRAXANE + gemcitabine) and 59 (carboplatin + gemcitabine) years. The primary endpoint of the phase II trial was investigator assessed progression free survival (PFS). Secondary endpoints evaluated in the study included overall survival (OS) and objective response rate (ORR).

Additional ABRAXANE Data Presented at SABCS

Additional investigator initiated studies presented at SABCS also evaluated the investigational uses of ABRAXANE in the neoadjuvant setting in patients with previously untreated breast cancer (GeparSepto; P5-16-03) and as induction and maintenance therapy for women with HER2-negative metastatic breast cancer (SNAP; P5-15-05).

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

Do not administer ABRAXANE therapy to patients who have baseline neutrophil counts of less than 1500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE
Note: An albumin form of paclitaxel may substantially affect a drug’s functional properties relative to those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS
CONTRADINDICATIONS

Neutrophil Counts

ABRAXANE should not be used in patients who have baseline neutrophil counts of < 1500 cells/mm3
Hypersensitivity

Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with the drug
WARNINGS AND PRECAUTIONS

Hematologic Effects

Bone marrow suppression (primarily neutropenia) is dose-dependent and a dose-limiting toxicity of ABRAXANE. In a clinical study, Grade 3-4 neutropenia occurred in 34% of patients with metastatic breast cancer (MBC)
Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Day 1
Do not administer ABRAXANE to patients with baseline absolute neutrophil counts (ANC) of less than 1,500 cells/mm3
In the case of severe neutropenia ( < 500 cells/mm3 for 7 days or more) during a course of ABRAXANE therapy, reduce the dose of ABRAXANE in subsequent courses in patients with MBC
Resume treatment with every-3-week cycles of ABRAXANE after ANC recovers to a level > 1500 cells/mm3 and platelets recover to > 100,000 cells/mm3
Nervous System

Sensory neuropathy is dose- and schedule-dependent
The occurrence of Grade 1 or 2 sensory neuropathy does not generally require dose modification
If ≥ Grade 3 sensory neuropathy develops, withhold until resolution to Grade 1 or 2 followed by a dose reduction for all subsequent courses of ABRAXANE
Hypersensitivity

Severe and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, have been reported
Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with this drug
Hepatic Impairment

Because the exposure and toxicity of paclitaxel can be increased with hepatic impairment, administration of ABRAXANE in patients with hepatic impairment should be performed with caution
Patients with hepatic impairment may be at an increased risk of toxicity, particularly from myelosuppression, and should be monitored for development of profound myelosuppression
For MBC, the starting dose should be reduced for patients with moderate or severe hepatic impairment
Albumin (Human)

ABRAXANE contains albumin (human), a derivative of human blood
Use in Pregnancy: Pregnancy Category D

ABRAXANE can cause fetal harm when administered to a pregnant woman
If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus
Women of childbearing potential should be advised to avoid becoming pregnant while receiving ABRAXANE
Use in Men

Men should be advised not to father a child while receiving ABRAXANE
ADVERSE REACTIONS

Randomized Metastatic Breast Cancer (MBC) Study

The most common adverse reactions (≥20%) with single-agent use of ABRAXANE vs paclitaxel injection in the MBC study are alopecia (90%, 94%), neutropenia (all cases 80%, 82%; severe 9%, 22%), sensory neuropathy (any symptoms 71%, 56%; severe 10%, 2%), abnormal ECG (all patients 60%, 52%; patients with normal baseline 35%, 30%), fatigue/asthenia (any 47%, 39%; severe 8%, 3%), myalgia/arthralgia (any 44%, 49%; severe 8%, 4%), AST elevation (any 39%, 32%), alkaline phosphatase elevation (any 36%, 31%), anemia (any 33%, 25%; severe 1%, < 1%), nausea (any 30%, 22%; severe 3%, < 1%), diarrhea (any 27%, 15%; severe < 1%, 1%) and infections (24%, 20%), respectively
Sensory neuropathy was the cause of ABRAXANE discontinuation in 7/229 (3%) patients
Other adverse reactions of note with the use of ABRAXANE vs paclitaxel injection included vomiting (any 18%, 10%; severe 4%, 1%), fluid retention (any 10%, 8%; severe 0%, < 1%), mucositis (any 7%, 6%; severe < 1%, 0%), hepatic dysfunction (elevations in bilirubin 7%, 7%), hypersensitivity reactions (any 4%, 12%; severe 0%, 2%), thrombocytopenia (any 2%, 3%; severe < 1%, < 1%), neutropenic sepsis ( < 1%, < 1%), and injection site reactions ( < 1%, 1%), respectively. Dehydration and pyrexia were also reported
Renal dysfunction (any 11%, severe 1%) was reported in patients treated with ABRAXANE (n=229)
In all ABRAXANE-treated patients (n=366), ocular/visual disturbances were reported (any 13%; severe 1%)
Severe cardiovascular events possibly related to single-agent ABRAXANE occurred in approximately 3% of patients and included cardiac ischemia/infarction, chest pain, cardiac arrest, supraventricular tachycardia, edema, thrombosis, pulmonary thromboembolism, pulmonary emboli, and hypertension
Cases of cerebrovascular attacks (strokes) and transient ischemic attacks have been reported
Postmarketing Experience With ABRAXANE and Other Paclitaxel Formulations

Severe and sometimes fatal hypersensitivity reactions have been reported with ABRAXANE. The use of ABRAXANE in patients previously exhibiting hypersensitivity to paclitaxel injection or to human albumin has not been studied
There have been reports of congestive heart failure, left ventricular dysfunction, and atrioventricular block with ABRAXANE, primarily among individuals with underlying cardiac history or prior exposure to cardiotoxic drugs
There have been reports of extravasation of ABRAXANE. Given the possibility of extravasation, it is advisable to monitor closely the ABRAXANE infusion site for possible infiltration during drug administration
DRUG INTERACTIONS

Caution should be exercised when administering ABRAXANE concomitantly with medicines known to inhibit or induce either CYP2C8 or CYP3A4
USE IN SPECIFIC POPULATIONS

Nursing Mothers

It is not known whether paclitaxel is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother
Pediatric

The safety and effectiveness of ABRAXANE in pediatric patients have not been evaluated
Geriatric

A higher incidence of epistaxis, diarrhea, dehydration, fatigue, and peripheral edema was found in patients 65 years or older who received ABRAXANE for MBC in a pooled analysis of clinical studies
Renal Impairment

There are insufficient data to permit dosage recommendations in patients with severe renal impairment or end stage renal disease (estimated creatinine clearance < 30 mL/min)
DOSAGE AND ADMINISTRATION

Do not administer ABRAXANE to any patient with total bilirubin greater than 5 x ULN or AST greater than 10 x ULN
Reduce starting dose in MBC patients with moderate to severe hepatic impairment
Dose reductions or discontinuation may be needed based on severe hematologic or neurologic toxicity
Monitor patients closely
Please see full Prescribing Information, including Boxed WARNING.