Celgene Release: Data Presented At ESMO 2016 Adds To Understanding Of Abraxane As A Therapy For Patients With Historically Challenging Solid Tumors

October 7, 2016 |

17 min read

Multiple presentations evaluate ABRAXANE alone or in combination with novel agents and novel regimens to treat mPAC, NSCLC, and MBC

SUMMIT, N.J.--(BUSINESS WIRE)--Celgene Corporation (NASDAQ:CELG) today announced results from multiple sponsored and independent studies will be presented during the European Society of Medical Oncology (ESMO) 2016 Annual Meeting evaluating the use of ABRAXANE^® (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) as a foundational treatment, either alone or in combination with novel agents and novel regimens, for patients with traditionally challenging cancers, including metastatic pancreatic cancer (mPAC), metastatic breast cancer (MBC) and advanced non-small cell lung cancer (NSCLC).

“Celgene continues to evaluate the safety and efficacy of ABRAXANE in patients with particularly challenging advanced diseases or with co-morbidities that limit their treatment options”

“Celgene continues to evaluate the safety and efficacy of ABRAXANE in patients with particularly challenging advanced diseases or with co-morbidities that limit their treatment options,” said Michael Pehl, President, Hematology and Oncology for Celgene. “These data continue to shape our understanding of these difficult to treat diseases which will help evolve the current and future treatment landscapes in areas where there have been historically limited treatment options available to patients.”

Investigational Research Evaluates ABRAXANE as a Foundational Treatment in mPAC, NSCLC, and MBC

The cancer treatment landscape has rapidly evolved over the last several years, with the introduction of targeted therapies and immunotherapy. While these advances have generated a lot of excitement, there are patients who may not benefit from these therapies. Celgene remains committed to continuing to explore treatments for these patients and at ESMO 2016, several studies evaluating treatment with ABRAXANE as a foundation therapy in these patients are being presented.

New data being presented from the ABOUND trials demonstrate the continued benefit of ABRAXANE/carboplatin doublet therapy in NSCLC. ABRAXANE is indicated for the first-line treatment of locally advanced or metastatic non–small cell lung cancer, in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy. The ABOUND trials included patients 70 years and older, as well as those with poorer performance status or squamous disease.^1,2,3

An interim analysis of the ABOUND.70+ study (Poster 1280P) will be presented that evaluated the quality of life impact of elderly patients (aged 70+) with advanced NSCLC and an ECOG status of 0 or 1 treated with an ABRAXANE + carboplatin regimen through 4 cycles of treatment.¹
The ABOUND.PS2 study (Poster 1278P) evaluated radiological response following treatment with ABRAXANE + carboplatin in 31 patients with advanced NSCLC and an Eastern Cooperative Oncology Group (ECOG) performance status 2.²
Similarly, interim quality of life results from the ABOUND.sqm study (Poster 1279P) will be presented that evaluated the quality of life in squamous NSCLC patients treated with ABRAXANE + carboplatin.³

Real-world outcomes data will also be presented for patients with metastatic breast cancer (MBC) including in the HR+/Her2- and TNBC subsets treated with ABRAXANE.^4,5

A study of 176 MBC patients (Poster 1030P) reports on time to treatment discontinuation (TTD) and time to next treatment (TTNT) with ABRAXANE compared with eribulin.⁴
Another retrospective analysis (Poster 1029P) will be presented that evaluated TTD in 411 MBC patients in the second line setting with ABRAXANE vs paclitaxel.⁵

The use of ABRAXANE in first line mPAC is further investigated by multiple independent studies being reported at ESMO.

Safety and efficacy results from novel Abraxane regimens like GABRINOX (Abraxane-gemcitabine followed by FOLFIRINOX), and PAXG (Abraxane, cisplatin, capecitabine and gemcitabine) are being reported at ESMO 2016 (Posters 679P and 681P).^6,7
Safety and efficacy data for Abraxane in patients with elevated bilirubin (posters 684P and 683P) will also be reported.^8,9

Investigating ABRAXANE as a Chemotherapy Foundation with Novel Agents

In addition, there is also emerging data that further evaluates ABRAXANE’s use in challenging oncological diseases which illustrates the medical interest in ABRAXANE as a chemotherapy foundation in research with novel agents.

Currently, there are 180 clinical studies evaluating ABRAXANE combinations, including novel agents.¹⁰ At this year’s ESMO, 15 independent studies are presented which evaluate ABRAXANE as a combination therapy with other agents across several tumor types including: TNBC – durvalumab (Poster 221TIP), mPAC - cisplatin, capecitabine, gemcitabine, FOLFIRINOX, ipafricept, vantictumab, PEGPH20, nivolumab (Posters 681P – Reni, 367PD – Weekes, 677P – Messersmith, 682P – Giommoni, and 715 TiP – Van Cutsem), and NSCLC – nivolumab, necitumumab (Posters 1059P – George and 1298 TiP – Socinski).

In addition, Celgene is presenting preliminary tolerability data evaluating the investigational combination use of ABRAXANE with the immunotherapy agent nivolumab (Poster 1059P) in NSCLC and mPAC. The study has been expanded and patients are currently enrolling in part 2. Additional data on the safety and efficacy of this combination in multiple tumor types will be presented at a future medical meeting.¹¹

Update of ESMO Clinical Practice Guidelines

The latest edition of ESMO lung cancer guidelines have been updated to recommend use of ABRAXANE + carboplatin in patients with stage IV NSCLC. The recommendation is based on the pivotal trial that was conducted for ABRAXANE.¹²

About ABRAXANE^®(nab-paclitaxel)

ABRAXANE^® is a nanotechnology agent that is currently the only albumin-based nanotechnology therapy approved for the treatment of metastatic breast cancer, non-small cell lung cancer and pancreatic cancer in the United States, Europe and other markets around the world. It contains albumin-bound paclitaxel nanoparticles and is manufactured using patented nab^® technology. ABRAXANE is formulated with albumin, a human protein, and is free of solvents.

ABRAXANE was first approved in January 2005 by the U.S. Food and Drug Administration (FDA) 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. In Europe, ABRAXANE was approved in January 2008 as monotherapy for the treatment of metastatic breast cancer in adult patients who have failed first-line treatment for metastatic disease and for whom standard, anthracycline containing therapy is not indicated. ABRAXANE is now approved in more than 50 countries for the treatment of metastatic breast cancer.

In October 2012, ABRAXANE was approved by the FDA for the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy. ABRAXANE is also approved for the treatment of NSCLC in Argentina, Australia, Chile, Ecuador, Guatemala, Hong Kong, Japan, New Zealand and Singapore.

In September 2013, the FDA approved ABRAXANE as first-line treatment of patients with metastatic adenocarcinoma of the pancreas, in combination with gemcitabine. In December 2013, ABRAXANE in combination with gemcitabine was approved for first-line treatment of adult patients with metastatic adenocarcinoma of the pancreas in Europe. ABRAXANE is also approved for the treatment of metastatic pancreatic cancer in more than 40 countries.

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

CONTRAINDICATIONS

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 clinical studies, Grade 3-4 neutropenia occurred in 34% of patients with metastatic breast cancer (MBC), 47% of patients with non–small cell lung cancer (NSCLC), and 38% of patients with pancreatic cancer
Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Day 1 (for MBC) and Days 1, 8, and 15 (for NSCLC and for pancreatic cancer)
Do not administer ABRAXANE to patients with baseline absolute neutrophil counts (ANC) of less than 1500 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 either MBC or NSCLC
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 a level >100,000 cells/mm³
In patients with NSCLC, resume treatment if recommended at permanently reduced doses for both weekly ABRAXANE and every-3-week carboplatin after ANC recovers to at least 1500 cells/mm³ and platelet count of at least 100,000 cells/mm³ on Day 1 or to an ANC of at least 500 cells/mm³ and platelet count of at least 50,000 cells/mm³ on Days 8 or 15 of the cycle
In patients with adenocarcinoma of the pancreas, withhold ABRAXANE and gemcitabine if the ANC is less than 500 cells/mm³ or platelets are less than 50,000 cells/mm³ and delay initiation of the next cycle if the ANC is less than 1500 cells/mm³ or platelet count is less than 100,000 cells/mm³ on Day 1 of the cycle. Resume treatment with appropriate dose reduction if recommended

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 ABRAXANE treatment until resolution to Grade 1 or 2 for MBC or until resolution to = Grade 1 for NSCLC and pancreatic cancer followed by a dose reduction for all subsequent courses of ABRAXANE

Sepsis

Sepsis occurred in 5% of patients with or without neutropenia who received ABRAXANE in combination with gemcitabine
Biliary obstruction or presence of biliary stent were risk factors for severe or fatal sepsis
If a patient becomes febrile (regardless of ANC), initiate treatment with broad-spectrum antibiotics
For febrile neutropenia, interrupt ABRAXANE and gemcitabine until fever resolves and ANC =1500 cells/mm³, then resume treatment at reduced dose levels

Pneumonitis

Pneumonitis, including some cases that were fatal, occurred in 4% of patients receiving ABRAXANE in combination with gemcitabine
Monitor patients for signs and symptoms and interrupt ABRAXANE and gemcitabine during evaluation of suspected pneumonitis
Permanently discontinue treatment with ABRAXANE and gemcitabine upon making a diagnosis of pneumonitis

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 and NSCLC, the starting dose should be reduced for patients with moderate or severe hepatic impairment
For pancreatic adenocarcinoma, ABRAXANE is not recommended for patients with moderate to severe hepatic impairment (total bilirubin >1.5 x ULN and AST =10 x ULN)

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

Non–Small Cell Lung Cancer (NSCLC) Study

The most common adverse reactions (=20%) of ABRAXANE in combination with carboplatin are anemia, neutropenia, thrombocytopenia, alopecia, peripheral neuropathy, nausea, and fatigue
The most common serious adverse reactions of ABRAXANE in combination with carboplatin for NSCLC are anemia (4%) and pneumonia (3%)
The most common adverse reactions resulting in permanent discontinuation of ABRAXANE are neutropenia (3%), thrombocytopenia (3%), and peripheral neuropathy (1%)
The most common adverse reactions resulting in dose reduction of ABRAXANE are neutropenia (24%), thrombocytopenia (13%), and anemia (6%)
The most common adverse reactions leading to withholding or delay in ABRAXANE dosing are neutropenia (41%), thrombocytopenia (30%), and anemia (16%)
The following common (=10% incidence) adverse reactions were observed at a similar incidence in ABRAXANE plus carboplatin–treated and paclitaxel injection plus carboplatin–treated patients: alopecia (56%), nausea (27%), fatigue (25%), decreased appetite (17%), asthenia (16%), constipation (16%), diarrhea (15%), vomiting (12%), dyspnea (12%), and rash (10%); incidence rates are for the ABRAXANE plus carboplatin treatment group
Adverse reactions with a difference of =2%, Grade 3 or higher, with combination use of ABRAXANE and carboplatin vs combination use of paclitaxel injection and carboplatin in NSCLC are anemia (28%, 7%), neutropenia (47%, 58%), thrombocytopenia (18%, 9%), and peripheral neuropathy (3%, 12%), respectively
Adverse reactions with a difference of =5%, Grades 1-4, with combination use of ABRAXANE and carboplatin vs combination use of paclitaxel injection and carboplatin in NSCLC are anemia (98%, 91%), thrombocytopenia (68%, 55%), peripheral neuropathy (48%, 64%), edema peripheral (10%, 4%), epistaxis (7%, 2%), arthralgia (13%, 25%), and myalgia (10%, 19%), respectively
Neutropenia (all grades) was reported in 85% of patients who received ABRAXANE and carboplatin vs 83% of patients who received paclitaxel injection and carboplatin

Pancreatic Adenocarcinoma Study

Among the most common (=20%) adverse reactions in the phase III study, those with a =5% higher incidence in the ABRAXANE/gemcitabine group compared with the gemcitabine group are neutropenia (73%, 58%), fatigue (59%, 46%), peripheral neuropathy (54%, 13%), nausea (54%, 48%), alopecia (50%, 5%), peripheral edema (46%, 30%), diarrhea (44%, 24%), pyrexia (41%, 28%), vomiting (36%, 28%), decreased appetite (36%, 26%), rash (30%, 11%), and dehydration (21%, 11%)
Of these most common adverse reactions, those with a =2% higher incidence of Grade 3-4 toxicity in the ABRAXANE/gemcitabine group compared with the gemcitabine group, respectively, are neutropenia (38%, 27%), fatigue (18%, 9%), peripheral neuropathy (17%, 1%), nausea (6%, 3%), diarrhea (6%, 1%), pyrexia (3%, 1%), vomiting (6%, 4%), decreased appetite (5%, 2%), and dehydration (7%, 2%)
Thrombocytopenia (all grades) was reported in 74% of patients in the ABRAXANE/gemcitabine group vs 70% of patients in the gemcitabine group
The most common serious adverse reactions of ABRAXANE (with a =1% higher incidence) are pyrexia (6%), dehydration (5%), pneumonia (4%), and vomiting (4%)
The most common adverse reactions resulting in permanent discontinuation of ABRAXANE were peripheral neuropathy (8%), fatigue (4%), and thrombocytopenia (2%)
The most common adverse reactions resulting in dose reduction of ABRAXANE are neutropenia (10%) and peripheral neuropathy (6%)
The most common adverse reactions leading to withholding or delay in ABRAXANE dosing are neutropenia (16%), thrombocytopenia (12%), fatigue (8%), peripheral neuropathy (15%), anemia (5%), and diarrhea (5%)
Other selected adverse reactions with a =5% higher incidence for all-grade toxicity in the ABRAXANE/gemcitabine group compared to the gemcitabine group, respectively, are asthenia (19%, 13%), mucositis (10%, 4%), dysgeusia (16%, 8%), headache (14%, 9%), hypokalemia (12%, 7%), cough (17%, 7%), epistaxis (15%, 3%), urinary tract infection (11%, 5%), pain in extremity (11%, 6%), arthralgia (11%, 3%), myalgia (10%, 4%), and depression (12%, 6%)
Other selected adverse reactions with a =2% higher incidence for Grade 3-4 toxicity in the ABRAXANE/gemcitabine group compared to the gemcitabine group are thrombocytopenia (13%, 9%), asthenia (7%, 4%), and hypokalemia (4%, 1%)

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 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

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Clinical research Phase III