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Drug Trials Snapshots: PORTRAZZA

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to the PORTRAZZA Prescribing Information for complete information.

PORTRAZZA (necitumumab)
por-tra-zuh
Eli Lilly
Approval date: November 24, 2015


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

PORTRAZZA is a drug used to treat a type of lung cancer called squamous non-small cell lung cancer (NSCLC) that has become advanced (metastatic). It is to be used in combination with two other cancer drugs, gemcitabine and cisplatin, in patients who have not previously received medication to treat advanced lung cancer.

PORTRAZZA is not indicated for treatment of non-squamous non-small cell lung cancer.

How is this drug used?

PORTRAZZA is given by a healthcare provider as an infusion into a vein, according to a specific schedule.

What are the benefits of this drug?

Patients taking PORTRAZZA plus gemcitabine and cisplatin lived longer on average (11.5 months) compared to those only taking gemcitabine and cisplatin (9.9 months).

What are the benefits of this drug (results of trials used to assess efficacy)?

The table and figure below summarize efficacy results for the clinical trial.

Table 3: Efficacy Results for Metastatic Squamous Non-Small Cell Lung Cancer

 PORTRAZZA PLUS GEMCITABINE AND CISPLATIN
N=545
GEMCITABINE AND CISPLATIN
 N=548
Overall Survival
Number of deaths (%)418 (77%)442 (81%)
Median – months (95% CI)a11.5 (10.4, 12.6)9.9 (8.9, 11.1)
Stratified Hazard Ratio (95% CI)0.84 (0.74, 0.96)
Stratified Log-rank p-value0.01
Progression-Free Survivalb
Number of events (%)431 (79%)417 (76%)
Median – months (95% CI)5.7 (5.6, 6.0)5.5 (4.8, 5.6)
Stratified Hazard Ratio (95% CI)0.85 (0.74, 0.98)
Stratified Log-rank p-value0.02

aAbbreviations: CI = confidence interval
bInvestigator assessed
PORTRAZZA Prescribing Information

Figure 4. Kaplan-Meier Curves of Overall Survival in Patients with Metastatic Squamous Non-Small Cell Lung Cancer

Figure summarizes efficacy result-overall survival for the clinical trial.

PORTRAZZA Prescribing Information

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

Subgroup analyses were conducted for sex, race and age.

  • Sex: PORTRAZZA worked similarly in men and women.
  • Race: The majority of patients in the clinical trial were white. Differences in response to PORTRAZZA among races could not be determined.
  • Age: PORTRAZZA worked better in patients below 70 years of age.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

The table below summarizes overall survival by subgroup.

Table 3. Subgroup Analysis of Overall Survival Intent to Treat Population

Table summarizes efficacy results by subgroup.

Clinical Trial Data

What are the possible side effects?

The most common side effects of PORTRAZZA are skin rash and magnesium deficiency (hypomagnesemia), which can cause muscular weakness, seizure, irregular heartbeats, and can be fatal.

Serious side effects of PORTRAZZA include increased risk of cardiac arrest, magnesium deficiency, blood clots in veins and arteries, skin rashes , reactions related to the infusion of the drug through the vein, toxicity to a fetus when given to a pregnant woman, and increased toxicity and increased death in patients with non-squamous NSCLC.

PORTRAZZA increases the risk of clotting events in blood vessels (including venous thromboembolism). Venous thromboembolism is the formation of blood clots in the vein. When a clot forms in a deep vein, usually in the leg, it is called a deep vein thrombosis or DVT. If that clot breaks loose and travels to the lungs, it is called a pulmonary embolism.

What are the possible side effects (results of trials used to assess safety)?

The tables below summarize adverse reactions, including electrolyte abnormalities, in the clinical trial.

Table 4. Adverse Reactions Occurring at Incidence Rate ≥5% All Grades or a ≥2% Grade 3-4 Difference Between Arms in Patients Receiving PORTRAZZA in Study 1

Adverse Reactions (MedDRA)
System Organ Class
PORTRAZZA Plus Gemcitabine and Cisplatin
N=538 (%)
Gemcitabine and cisplatin
N=541 (%)
All Grades
(Frequency %)
Grade 3-4
(Frequency %)
All Grades
(Frequency %)
Grade 3-4
(Frequency %)
Skin and Subcutaneous Tissue Disorders
Rash44460.2
Dermatitis Acneiform1510.60
Acne90.40.60
Pruritus70.20.90.2
Dry Skin7010
Skin fissures50.400
Gastrointestinal Disorders
Vomiting293250.9
Diarrhea162111
Stomatitis11160.6
Investigations
Weight decreased130.760.6
Respiratory, Thoracic and Mediastinal Disorders
Hemoptysis10150.9
Pulmonary embolisma5422
Nervous System Disorders
Headache11060.4
Vascular Disorders
Venous Thromboembolic Events (VTE)b9553
Infections and Infestations
Paronychia70.40.20
Eye Disorders
Conjunctivitisc70.420

a Pulmonary embolism is also included in the composite term venous thromboembolic events under system organ class vascular disorders.
b VTE is a composite term which includes: pulmonary embolism, deep vein thrombosis, thrombosis, mesenteric veins thrombosis, pulmonary artery thrombosis, pulmonary venous thrombosis, venous thrombosis limb, axillary vein thrombosis, thrombophlebitis, thrombosis in device, vena cava thrombosis, venous thrombosis, subclavian vein thrombosis, superior vena cava syndrome, and thrombophlebitis superficial.
c Conjunctivitis is a composite term that includes conjunctivitis, eye irritation, vision blurred, conjunctivitis bacterial, dry eye, visual acuity reduced, blepharitis, allergic blepharitis, conjunctiva hemorrhage, eye infection, eye pain, lacrimation increased, ocular hyperemia, Sjogren’s syndrome, visual impairment, and eye pruritus.
PORTRAZZA Prescribing Information

Table 5. Thromboembolic Events by Age Group

 <70>≥70
GC+N
N=432
n (%)
GC
N=444
n (%)
GC+N
N=106
n (%)
GC
N=444
n (%)
Any GradeGr ≥3Any GradeGr ≥3Any GradeGr≥3Any GradeGr ≥3
Arterial thromboembolic events23 (5.3)15 (3.5)15 (3.4)7 (1.6)6 (5.7)6 (5.7)6 (6.2)4 (4.1)
Venous thromboembolic events36 (8.3)21 (4.9)25 (5.6)11 (2.5)13 (12.3)6 (5.7)4 (4.1)3 (3.1)

GC=Gemcitabine-Cisplatin
GC+N= Gemcitabine-Cisplatin plus Necitumumab
Gr=grade
Clinical Trial Data

Table 6. Electrolyte Abnormalities according to Laboratory Assessment at Incidence Rate >10% and a >2% Difference between Arms in Patients Receiving PORTRAZZA in Study 1a

LABORATORY PARAMETERPORTRAZZA Plus Gemcitabine and Cisplatin
N=538
Gemcitabine and cisplatin
N=541
NaAll Grades
(Frequency %)
Grade 3 or 4
(Frequency %)
NaAll Grades
(Frequency %)
Grade 3 or 4
(Frequency %)
Hypomagnesemia4618320457707
Hypokalemia505285505183
Hypocalcemia502456499302
Hypocalcemia (albumin corrected)477364480232
Hypophosphatemia462318454236

aOnly patients with baseline and at least one post-baseline result are included.
PORTRAZZA Prescribing Information

Were there any differences in side effects among sex, race and age?

Subgroup analyses were conducted for sex, race and age.

  • Sex: The risk of side effects was similar in men and women.
  • Race: The majority patients in the clinical trial were white. Differences in side effects among races could not be determined.
  • Age: The risk of overall side effects was similar in patients below and above 65 years of age. The risk of venous thromboembolism was higher in patients age 70 and over compared to those who were younger than age 70.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

The table below summarizes adverse events during the clinical trial by subgroup.

Table 7. Subgroup Analysis of Treatment-Emergent Adverse Events (Safety Population)

 Gemcitabine-Cisplatin Chemotherapy Plus NecitumumabGemcitabine-Cisplatin Chemotherapy Alone
Demographic Subgroupn%Total, Nn(%)Total, N
Any TEAEs      
Sex
Male44197.645244399.3446
Female8898.9899097.892
Age Group
<17>  0  0
>=17 - <65>32597.333432599.1328
>= 65 years20498.620720899210
>= 75 years1910019249625
Race
White44297.845244798.9452
Black or African American6100651005
Asian3895404110041
American Indian or Alaska Native  011001
Native Hawaiian or Other Pacific Islander11001  0
Other42100423910039
Ethnicity
Hispanic or Latino54100545498.255
Not Hispanic or Latino47397.548547899.2482
Missing2100211001

Clinical Trial Data

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved PORTRAZZA based on evidence from a clinical trial of 1093 patients. The trials were conducted at 184 clinical sites across North America (including the United States), South America, Europe, Australia, Africa, and Asia.

Figure 1 summarizes how many men and women were enrolled in the clinical trial.

Figure 1. Baseline Demographics by Sex

Pie chart summarizing how many men and women were in the clinical trial of the drug PORTRAZZA.  In total, 908 men (83%) and 185 women (17%) participated in the clinical trial used to evaluate the drug PORTRAZZA.

Clinical Trial Data

Figure 2 and Table 1 summarize how many patients by race were enrolled in the clinical trial.

Figure 2. Baseline Demographics by Race

Pie chart summarizing the percentage of patients by race enrolled in the PORTRAZZA clinical trial. In total, 913 Whites (83%), 11 Blacks (1%), 85 Asian (8%), and 84 Other (8%), participated in the clinical trial.

Table 1. Baseline Demographics by Race

RaceNumber of PatientsPercentage
White91383%
Black or African American111%
Asian858%
American Indian or Alaska Native1<>
Native Hawaiian or Other Pacific Islander1<>
Other828%

Clinical Trial Data

The figure below summarizes how many patients by age were enrolled in the clinical trial.

Figure 3. Baseline Demographics by Age

Pie chart summarizing how many individuals of certain age groups were enrolled in the PORTRAZZA clinical trial.  In total, 672 participants were below 65 years old (61%) and 421 participants were 65 and older (39%).

Clinical Trial Data

Who participated in the trials?

The table below summarizes demographics of patients in the clinical trial.

Table 8. Baseline Demographics of Patients in the Clinical Trial

 Comparator/Control Gemcitabine-Cisplatin Chemotherapy Alone
 (N=548)
Treatment Group
Gemcitabine-Cisplatin Chemotherapy Plus Necitumumab
(N=545)
Total 

    (N=1093)
Demographic Parametersn%n%n (%)
Sex
Male458(83.6)450(82.6)908 (83.1)
Female90(16.4)95(17.4)185 (16.9)
Age
Mean years (SD)61.7(8.20)62.0(8.32)61.8 (8.26)
Median (years)62.0 62.0 62.0
Min, Max (years)32, 86 32, 84 32, 86
Age Group
>=17 - <65>340(62.0)332(60.9)672 (61.5)
>=65 years208(38.0)213(39.1)421 (38.5)
>= 75 years19(3.5)25(4.6)44 (4.0)
Race
White456(83.2)457(83.9)913 (83.5)
Black or African American6(1.1)5(0.9)11 (1.0)
Asian42(7.7)43(7.9)85 (7.8)
American Indian or Alaska Native0 1(0.2)1 (0.1)
Native Hawaiian or Other Pacific Islander1(0.2)0 1 (0.1)
Other43(7.8)39(7.2)82 (7.5)

Clinical Trial Data

How were the trials designed?

The benefit and side effects of PORTRAZZA were evaluated in a clinical trial of patients with advanced squamous Non-Small Cell Lung Cancer (NSCLC). The patients were randomly assigned to receive gemcitabine and cisplatin, either with or without PORTAZZA. Both patients and healthcare workers knew which treatment was being administered. The efficacy of PORTRAZZA was evaluated by measuring how long patients survived.

How were the trials designed?

The pivotal trial was a randomized, multi-center open-label, controlled trial conducted in patients receiving gemcitabine and cisplatin first-line chemotherapy for metastatic squamous NSCLC. Patients were randomized (1:1) to receive PORTRAZZA plus gemcitabine and cisplatin or gemcitabine and cisplatin alone. Stratification factors were ECOG performance status (0, 1 versus 2) and geographic region (North America, Europe, and Australia versus South America, South Africa, and India versus Eastern Asia).

Gemcitabine (1250 mg/m2, Days 1 and 8) plus cisplatin (75 mg/m2, Day 1) were administered every 3 weeks (1 cycle) for a maximum of 6 cycles in the absence of disease progression or unacceptable toxicity. PORTRAZZA (800 mg by intravenous infusion on Days 1 and 8 of each 3-week cycle) was administered prior to gemcitabine and cisplatin.

Patients demonstrating at least stable disease on PORTRAZZA plus gemcitabine and cisplatin were to continue PORTRAZZA as a single agent in the absence of disease progression or unacceptable toxicity after completion of 6 planned courses of chemotherapy or if chemotherapy was discontinued for toxicity. The main outcome measure was overall survival (OS). Investigator-assessed progression-free survival (PFS) and overall response rate (ORR) were also assessed.

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

PRESCRIBING INFORMATION

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