On February 27,2016 Celgene Corporation (NASDAQ:CELG) reported that two interim analyses of exploratory quality of life (QoL) endpoints in the ongoing phase III ABOUND.sqm clinical study investigating ABRAXANE (paclitaxel protein-bound particles for injectable suspension)(albumin-bound) in patients with advanced, squamous non-small cell lung cancer (NSCLC) were presented at the 2016 ASCO (Free ASCO Whitepaper) Quality Care Symposium (Press release, Celgene, FEB 27, 2016, View Source [SID:1234509247]).
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In the ABOUND.sqm study, patients received four 21-day cycles of ABRAXANE (100 mg/m2 on days 1, 8 and 15) plus carboplatin (AUC6 on day 1) and those with a response or stable disease could be randomized to receive either ABRAXANE (100 mg/m2 on days 1, 8) plus best supportive care or best supportive care alone in 21-day cycles until disease progression.
The analyses included 159 patients from the study who were evaluable for radiological response and QoL. In the two analyses 99% of patients had an ECOG performance status of 0-1 and pre-defined QoL measures including the LCSS (Global Score, Average Total Score, 3-Item Index, Average Symptom Burden Index and Lung Cancer Symptoms) and EuroQol EQ-5D-5L assessment were taken on day one of each cycle during the initial treatment phase.
The first analysis evaluated the therapeutic impact of chemotherapy on patient symptoms and activities. For all patients in the analysis, quality of life as measured by the LCSS and EuroQoL (EQ-5D-5L) was generally either maintained or improved throughout the entire treatment course.
The second analysis assessed the impact of radiological response on Quality of Life. In this analysis, 93/159 patients had an unconfirmed radiological response and 66/159 did not. Responders had a greater improvement in lung cancer symptom score, as measured by the LCSS and EQ-5D-5L scores.
Importantly, among patients who reported problems with mobility, self care, usual activities of living, pain/discomfort, or anxiety/depression prior to treatment, 38 – 47% reported complete resolution of these problems at least once during treatment. This was more pronounced in patients who achieved a radiological response, with complete resolution at least once reported in 42 – 59% of patients.
"Inclusion of quality of life measures is particularly important when so few prospective trials in advanced non-small cell lung cancer currently include such analyses," said Dr. Corey Langer of the University of Pennsylvania and lead investigator of one of the analyses. "These data demonstrate a correlation between radiologic response and patient reported quality of life."
Indication
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.
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 < 1500cells/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 47% of patients with non-small cell lung cancer (NSCLC)
Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Days 1, 8, and 15
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 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
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 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 NSCLC, 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
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
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
Myelosuppression, peripheral neuropathy, and arthralgia were more frequent in patients ≥65 years of age treated with ABRAXANE and carboplatin in NSCLC
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 NSCLC 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.