Optimizing Nursing Management
of Patients Receiving Novel
Therapies for Advanced NSCLC
Beth Eaby-Sandy, MSN, CRNP, OCN®
Nurse Practitioner
Abramson Cancer Center of the University of Pennsylvania
Disclosure of Conflicts of Interest
Beth Eaby-Sandy, MSN, CRNP, OCN® discloses she was a
member of the advisory board of Boehringer Ingelheim and
a member of the speakers’ bureau of Genentech in the last
12 months. She is currently a member of the speakers’
bureau of Lilly.
NSCLC: Scope of the Problem
Estimated New Cancer Cases in 2013
• Prostate: 238,590 (28%)
• Lung/Bronchus: 118,080 (14%)
• Colon/Rectum: 73,680 (9%)
• Breast: 226,870 (29%)
• Lung/Bronchus: 110,110 (14%)
• Colon/Rectum: 69,140 (9%)
ACS, 2013.
NSCLC: Scope of the Problem
Estimated New Cancer Cases in 2013
• Prostate: 238,590 (28%)
• Lung/Bronchus: 118,080 (14%)
• Colon/Rectum: 73,680 (9%)
• Breast: 226,870 (29%)
• Lung/Bronchus: 110,110 (14%)
• Colon/Rectum: 69,140 (9%)
PERSPECTIVE
Lung/Bronchus Deaths = 159,480
Breast, Prostate, Colon/Rectum, and Pancreatic Deaths = 158,630
ACS, 2013.
Lung Cancer Stages and Survival
2003-2009, All Races, Both Sexes
Stage Distribution (%)
5-Year Relative Survival (%)
60
Percent
50
40
30
20
10
0
Localized (confined to primary Regional (spread to regional
site)
lymph nodes)
Stage
SEER Data, 2003-2009.
Distant (cancer has
metastasized)
Unknown (unstaged)
NSCLC: Breakdown by Subtype
 Squamous
(30-35%)
– Usually more
centralized
– More frequently
associated with
significant cough and
hemoptysis
Eaby-Sandy, 2011.
NSCLC: Breakdown by Subtype
 Nonsquamous
(65%)
– Adenocarcinoma (40%)
• Most common type of
NSCLC
• Most common type in
nonsmokers
– Large cell carcinoma (15%)
– Mixed or NOS (10%)
NOS = not otherwise specified.
Eaby-Sandy, 2011.
NSCLC: Why Does Histology Matter?
 In
past, all NSCLC patients treated the same
 Data
have shown that the use of certain
agents in certain histologies results in
improved survival and response rates
 Histology
may predict the presence of
biomarkers
 Safety
parameters of certain treatments
depend on histology
NCCN, 2013.
NSCLC: Breakdown of Biomarkers
1%
3%
3%
Unknown
KRAS
3% 2%
EGFR
5%
ALK
RET
5%
MET
33%
PI3K
BRAF
15%
HER2
PDGFR
VEGFR
25%
FGFR1
AKT1
MEK1
ROS1
Hirsch, 2012.
Molecular Abnormalities in NSCLC
With Current Implications
EGFR
• Transmembrane receptor
• Detectable in about 80-85% of patients
• Level of expression varies widely
• Mutations in this domain (10-15% of pts) result in activation of the tyrosine
kinase domain with significantly better response to erlotinib or gefitinib
• Mutations: highest incidence in never smokers, adenocarcinoma, women,
and patients with Asian ethnicity
KRAS
•
•
•
•
EML4-ALK
• Incidence of EML4-ALK translocation: 2-7%
• Estimated prevalence of EML4-ALK in lung cancer: 6,000 pts/yr US; up to
40,000 pts/yr globally
• Most EML4-ALK fusion events observed in lung adenocarcinoma specimens
vs squamous or small cell histologies
• EML4-ALK rarely coexists with EGFR, HER2, or KRAS mutations, indicating it
is a distinct disease subtype
25% of North American population
Associated with smoking and resistance to tyrosine kinase inhibitors
KRAS mutations associated with shorter survival
Therapy with drugs other than erlotinib should be considered first
NCCN, 2013; Langer et al, 2010.
Why Do Biomarkers Matter?

PFS with standard chemotherapy regimens in NSCLC:
– Pemetrexed/cisplatin: 5 months
– Paclitaxel/carboplatin/bevacizumab: 6 months

PFS with EGFR mutated NSCLC receiving EGFR targeted
therapy:
– Gefitinib: 9.5 months
– Erlotinib: 9.7 months
– Afatinib: 11.0 months

PFS with ALK-positive NSCLC receiving ALK inhibitor:
– Crizotinib: 9.7 months
PFS = progression-free survival.
Camidge et al, 2012; Yang, Shih et al, 2012; Rosell et al, 2012; Fukuoka et al, 2011;
Scagliotti et al, 2008; Sandler et al, 2006.
Patient Factors in Treatment Planning

Patient ECOG PS
– PS is a predictor of survival/tolerating chemotherapy
– PS 0/1 patients tolerate chemotherapy best
– PS 2 patients can potentially benefit, even from
doublet chemotherapy; however, toxicity must be
monitored closely

Comorbidities
– Diabetes, heart disease
– Renal disease
ECOG PS = Eastern Cooperative Oncology Group performance status.
Rodriguez & Lilenbaum, 2008.
Patient Factors in Treatment Planning
 Patient
goals for treatment
– Quality-of-life issue (eg, hair loss)
– Advanced directives
 Demographics
 Social
support
– Involve social worker
– Counseling services
– Nutrition services
 Financial
issues
Evolving Supportive Care Paradigms

Early palliative care leads to increase in OS in
patients with metastatic NSCLC

Increased quality of life, less depressive symptoms

Improved understanding of diagnosis
– 1/3 patients at diagnosis thought they had curable disease
– Less likely to receive chemotherapy near end of life
OS = overall survival.
Temel et al, 2011; Temel et al, 2010.
Case Study: First-Line Treatment
Mrs. JF: History

68-year-old woman, presented 1 month ago with pain in her
lower back

Initial management with NSAIDs somewhat helpful; however, the
pain persisted and an x-ray of the lower spine was ordered

X-ray did not show bone abnormality but revealed a right lung
mass at the right lung base

Further imaging with PET/CT revealed a right lung mass,
mediastinal lymphadenopathy, bone metastases in the lumbar
spine, and liver metastases
– X-rays are often negative
NSAIDs = nonsteroidal antiinflammatory drugs;
PET/CT = positron emission tomography/computed tomography.
Mrs. JF: Diagnostic Evaluation

Treating physician referred patient to
pulmonologist for a bronchoscopy with biopsy
– Mediastinal lymph node was positive for NSCLC,
adenocarcinoma histology

MRI scan of the brain negative for metastatic
disease

Baseline labs within normal limits

Baseline PS 1

What factors important in treatment planning?
MRI = magnetic resonance imaging.
Mrs. JF: Treatment Considerations

Bronchoscopy yielded core biopsy, able to perform KRAS,
EGFR, ALK, and ROS testing. All were negative.

Patient has a 45-pack-year smoking history, currently trying
to quit

Patient has hypertension (controlled with medication),
hypercholesterolemia, and chronic obstructive pulmonary
disease

No significant weight loss, no hemoptysis

Understands incurable, no advanced directive, would like to
“fight”
Mrs. JF: Treatment Selection

Standard chemotherapy in biomarker-negative
patient appropriate therapy

Numerous options available for chemotherapy

Platinum based chemotherapy appropriate given
good PS

Is hair loss an issue?

Does she want to enroll in a clinical trial?
NCCN, 2013.
Mrs. JF: Treatment Selection
 Cisplatin
versus carboplatin? In US, often use
carboplatin in frontline therapy
 What
drug to pair with carboplatin? Toxicity?
– Pemetrexed
– Paclitaxel
– Docetaxel
– nab-paclitaxel
– Gemcitabine
– Vinorelbine
ECOG 1594: All Platinum Doublets
Essentially Equal

1,207 patients, stage IIIB/IV (15/85%),
PS 0-2

Median age 63; male/female: 64/36%
R
A
N
D
O
M
I
Z
E
Cisplatin
Paclitaxel
75 mg/m2 D2
135 mg/m2/24h
q3w
Cisplatin
Gemcitabine
100 mg/m2 D1
1 g/m2 D1,8,15
q4w
Cisplatin
Docetaxel
75 mg/m2 D1
75 mg/m2 D1
q3w
Carboplatin
Paclitaxel
AUC=6 mg/mL/min D1
q3w
225 mg/m2/3h D1
AUC = area under the curve.
Schiller et al, 2002.
Similar efficacy
for all doublets
Importance of Histology
Overall Survival for Pemetrexed/Cisplatin Versus
Gemcitabine/Cisplatin in First-Line Adenocarcinoma Patients
Median OS (months)
(95% CI)
CI = confidence interval.
Scagliotti et al, 2008; Scagliotti & Novello, 2003.
Pemetrexed
/Cisplatin
Gemcitabine
/Cisplatin
(n=436)
(n=411)
12.6
(10.7-13.6)
10.9
(10.2-11.9)
What About Bevacizumab?

Targeted therapy that can be added to chemotherapy in metastatic
NSCLC
 Eligibility criteria and warnings:
–
–
–
–
–
–
–
–
–
–
–
Nonsquamous histology only
No history hemoptysis (postprocedure ok?)
No recent history of arterial thrombotic event
No uncontrolled hypertension
Nephrotic syndrome (proteinuria ≥3.5gm)
No surgery within 28 days
Gastrointestinal perforation
Non-gastrointestinal fistula formation
Reversible posterior leukoencephalopathy syndrome
Infusion reactions
Ovarian failure
Avastin® prescribing information, 2013.
E4599 Trial: Bevacizumab + PC Versus PC
Alone in First-Line Nonsquamous NSCLC
1-year survival:
51% vs 44%
2-year survival:
23% vs 15%
PC = paclitaxel + carboplatin.
Sandler et al, 2006; Sandler et al, 2011.
Median OS with
Bevacizumab + PC
was 12.3 months vs
10.3 months for PC
alone (P=0.013)
PointBreak Trial: Can Regimens
Be Combined?

Randomized, open-label, phase III superiority study conducted in US

Pemetrexed 500 mg/m2; carboplatin AUC 6; bevacizumab 15 mg/kg

Paclitaxel 200 mg/m2; carboplatin AUC 6; bevacizumab 15 mg/kg
Inclusion:
− No prior systemic
therapy for lung cancer
− PS 0/1
− Stage IIIB-IV
nonsquamous NSCLC
− Stable treated brain
metastasized
R
1:1
Exclusion:
− Peripheral neuropathy
≥grade 1
− Uncontrolled pleural
effusions
q21d= every 21 days; PD = progressive disease.
Patel et al, 2012.
Induction Phase
q21d, 4 cycles
Maintenance Phase
q21d until PD
Pemetrexed
+ Carboplatin
+ Bevacizumab
Pemetrexed
+ Bevacizumab
450 Patients Each
Paclitaxel
+ Carboplatin
+ Bevacizumab
Bevacizumab
PointBreak Trial: OS Did Not Differ
Between Treatment Arms
PointBreak: KM OS From Randomization (ITT)
ITT = intent to treat; KM = Kaplan-Meier.
Patel et al, 2012.
Which Regimen to Choose for
First-Line Treatment?
 Discuss
toxicity profiles of different regimens
 Take
histology into account
 Give
patients autonomy to decide
– Do they want treatment?
– If so, which regimen’s toxicity profile is right for
them?
– Comorbidities? Diabetes? Coronary artery
disease? Renal insufficiency?
Maintenance Therapy
 If
no disease progression after first-line
chemotherapy, continue the chemotherapy
and/or targeted agent?
 We
know that in NSCLC continuing platinum
chemotherapy past 4 to 6 cycles does not
improve survival, just increases toxicity
 However,
three drugs have shown
improvement in PFS in the maintenance
setting
NCCN, 2013.
E4599 Trial: Bevacizumab + PC Versus PC Alone in
First-Line Nonsquamous NSCLC
First-line treatment
of patients with
stage IIIB and
malignant pleural
effusion, stage IV,
or recurrent
NSCLC
(N=878)
Stratified by
• Disease stage
• Degree of weight
loss
• Prior radiotherapy
• Measurable disease
q3w = every 3 weeks; IV = intravenously.
Sandler et al, 2006.
Paclitaxel 200 mg/m2 +
carboplatin AUC=6
q3w x 6
(no crossover permitted)
(n=444)
Bev 15 mg/kg
Solution for IV infusion
q3w + PC x 6
(n=434)
Continued until
progression or
unacceptable
toxicity
Bev 15 mg/kg IV
q3w until disease
progression or
unacceptable
toxicity
Primary
end point
OS
Secondary
end points
Response rate, PFS, toxicity
Maintenance Pemetrexed
Both studies showed improvement in OS when either switching or continuing on with
maintenance pemetrexed after first-line induction platinum-based chemotherapy.
Ciuleanu et al, 2009; Paz-Ares et al, 2012.
PointBreak Trial: Data Did Not Favor
Either Maintenance Regimen

Randomized, open-label, phase III superiority study conducted in US

Pemetrexed 500 mg/m2; carboplatin AUC 6; bevacizumab 15 mg/kg

Paclitaxel 200 mg/m2; carboplatin AUC 6; bevacizumab 15 mg/kg
Inclusion:
− No prior systemic
therapy for lung cancer
− PS 0/1
− Stage IIIB-IV
nonsquamous NSCLC
− Stable treated brain
metastasized
Exclusion:
− Peripheral neuropathy
≥grade 1
− Uncontrolled pleural
effusions
Patel et al, 2012.
R
1:1
Induction Phase
q21d, 4 cycles
Maintenance Phase
q21d until PD
Pemetrexed
+ Carboplatin
+ Bevacizumab
Pemetrexed
+ Bevacizumab
450 Patients Each
Paclitaxel
+ Carboplatin
+ Bevacizumab
Bevacizumab
SATURN Trial: Erlotinib Maintenance
Chemotherapy-naive,
advanced NSCLC
N=1,949
4 cycles of
first-line
platinum-based
doublet
Non-PD
n=889
Mandatory
tumor sampling
 SATURN included patients with the following tumor types:
– Squamous cell carcinoma
– Nonsquamous cell carcinoma (adenocarcinoma, large cell, other)
 Coprimary end points:
– PFS in all patients
– PFS in patients with EGFR IHC-positive tumors
 Secondary end points:
– OS in all patients and those with EGFR IHC-positive tumors
– OS and PFS in EGFR IHC-negative tumors
– Safety
IHC = immunohistochemistry.
Cappuzzo et al, 2010.
Erlotinib
150 mg/d
n=438
Placebo
n=451
PD
PD
SATURN Trial: Erlotinib Maintenance
19% reduction in risk of death
OS in a broad ITT population
OS rates in the SATURN ITT population at milestone
Erlotinib (n=438)
1.0
Overall Survival Probability
Placebo (n=451)
0.8
HR=0.81
95% CI:0.70-0.95; P=0.0088
0.6
Median 12.0 months with erlotinib
vs 11.0 months with placebo
0.4
0.2
11.0 months
median OS
12.0 months
median OS
0
0
3
HR = hazard ratio.
Cappuzzo et al, 2010.
6
9
12
15
18
21
Time (months)
24
27
30
33
36
Maintenance Treatment Conclusions

Again, there are options, just like first-line
chemotherapy choice

Do patients want a break or wish to continue?

Toxicity profile
– Pemetrexed is chemotherapy: potential for lowering of
blood counts, requires vitamin supplementation
– Bevacizumab and erlotinib are targeted agents, with
the potential for hypertension/cardiac toxicity, rash

Cost? Should this be an issue?

Insurance coverage/denials?
Case Study: Biomarker-Positive Patient
Ms. LT: History
 47-year-old
woman who had a cough for
2 months. Antibiotics and antihistamines did
not improve her symptoms.
 Chest
x-ray revealed multiple small masses
in bilateral lungs and pleural effusion,
confirmed by CT; PET/CT revealed no other
disease outside of chest
 MRI
scan of brain negative for metastatic
disease
Ms. LT: Diagnostic Evaluation
 Pleural
fluid positive for adenocarcinoma
histology; however, not enough for molecular
analysis
 Bronchoscopy/endobronchial
ultrasound
performed; able to biopsy mediastinal lymph
node to get more tissue
 Molecular
testing revealed an exon 19
deletion EGFR mutation
 Patient
is a never smoker with no significant
medical history or comorbidities
EGFR-Positive NSCLC:
CT Chest Scan at Diagnosis
Image courtesy of Beth Eaby-Sandy, MSN, CRNP, OCN®
Ms. LT: Treatment Considerations
 Chemotherapy
versus targeted therapy in
first-line treatment?
 How
long did it take to receive the molecular
testing results?
 Toxicity
 Current
profiles, how do they differ?
approved EGFR tyrosine kinase
inhibitors: gefitinib (no longer approved in
US), erlotinib, and afatinib
EURTAC Trial
First-Line Erlotinib Versus Chemotherapy in EGFR
Mutation-Positive NSCLC Patients
Rosell et al, 2012.
Another EGFR Inhibitor
 Afatinib
– Irreversible pan-EGFR/HER inhibitor
• Approved in July 2013 for first-line treatment of EGFR
mutation-positive metastatic NSCLC
– Dose is 40 mg daily, orally
Yang, Shih et al, 2012.
Primary End Point: PFS
Independent review ‒ All Randomly Assigned Patients
Progression-Free Survival (probability)
1.0
Afatinib
n=230
Cis/pem
n=115
PFS event, n (%) 152 (66)
0.8
Median PFS (months)
11.1
HR
(95% CI)
0.6
69 (60)
6.9
0.58 (0.43–0.78)
P=0.0004
47%
0.4
0.2
22%
0.0
0
Number at risk
Afatinib
230
Cis/Pem
115
3
6
9
12
15
18
21
24
27
10
2
3
0
0
0
Progression-Free Survival (months)
180
72
151
41
Yang, Schuler et al, 2012; Yang, Shih et al, 2012.
120
21
77
11
50
7
31
3
Ms. LT: Treatment Selection
 The
patient is treated with erlotinib, first line
 Dose
is 150 mg daily on an empty stomach
 Most
common toxicities in erlotinib arm:
– Papulopustular rash: 80% (grade 3= 13%)
– Diarrhea: 57% (grade 3=5%)
– Fatigue: 57% (grade 3=6%)
– Anorexia 31% (grade 3=0%)
Rosell et al, 2012.
Incidence and Severity of Rash
Drug
All Rash Incidence
Grade 3/4 Incidence
Cetuximab
89%
(70% in FLEX trial)
12%
(10% in FLEX trial)
Erlotinib
75%
9%
Gefitinib
Rash: 43%
Acne: 25%
0% (only reported ≥5%)
0%
Panitumumab
89%
12%
Afatinib
89%
16%
Erbitux® prescribing information, 2013; Tarceva® prescribing information, 2010; Iressa® prescribing information, 2010;
Vectibix® prescribing information, 2013; Yang, Shih et al, 2012.
Strategies to Prevent Dermatologic
Toxicities: Pre-Emptive
 STEPP
in metastatic colorectal cancer
patients who received panitumumabcontaining regimens
95 total patients:
– Significant improvement in EGFR rash and quality of
life with pre-emptive doxycycline and topical
hydrocortisone cream.
– At 6 weeks, grade ≥2 skin toxicities were reduced by
more than 50% in the pre-emptive arm
STEPP = Skin Toxicity Evaluation Protocol With Panitumumab.
Lacouture et al, 2010.
MASCC Rash Prevention and
Treatment Guidelines
Preventive
(Weeks 1-6,8 of
EGFR Inhibitor
initiation)
Recommend
Not Recommended
Level of
Evidence
Recommendation
Grades
Comments
Topical
Hydrocortisone 1%
cream with moisturizer
and sunscreen BID
• Pimecrolimus 1%
cream
• Tazarotene 0.05%
cream
• Sunscreen as single
agent
IIa
C
Doxycycline is
preferred in
patients with renal
impairment.
Minocycline is less
photosensitizing.
Systemic
• Minocycline 100 mg
daily
• Doxycyline 100 mg
BID
Tetracycline 550 mg
BID
IIa
A
Topical
• Alclometasone
0.05% cream
• Fluocinonide 0.05%
cream BID
• Clindamycin 1%
Vitamin K1 Cream
IVa
C
Fluocinonide
0.05% cream BID
should not be used
on the face for
more than 2 weeks
at a time.
Systemic
• Doxycycline 100
mg BID
• Minocycline 100 mg
daily
• Isotretinoin at low
doses (20-30 mg/d)
Acitretin
IVa
C
Isotretinoin is
photosensitizing
and can cause
xerosis. Monitor
lipids and liver
enzymes with
retinoids.
aEGFR
inhibitor study. MASCC = Multinational Association of Supportive Care in Cancer. BID = twice daily.
Lacouture et al, 2011.
Mild Rash
Image courtesy of Beth Eaby-Sandy, MSN, CRNP, OCN®
Moderate Rash
Image courtesy of Beth Eaby-Sandy, MSN, CRNP, OCN®
Severe Rash
Image courtesy of Beth Eaby-Sandy, MSN, CRNP, OCN®
Other Cutaneous Toxicities

Alopecia/scalp rash

Paronychia

Hypertrichosis

Fissures
Images courtesy of Beth Eaby-Sandy, MSN, CRNP, OCN®
Case Study: Older Adult With NSCLC
Mr. PD: History

Patient is an 80-year-old fit man who developed
increased shortness of breath and cough during
the past 6 months, though hemoptysis is what
led him to the emergency department

CT scan of the chest reveals a large, central
lung mass as well as adrenal metastases

He is a lifelong cigarette smoker, 1 pack per day

CT-guided needle biopsy reveals squamous cell
NSCLC
Mr. PD: Diagnostic Evaluation
 Brain
MRI scan shows a single brain
metastasis 1.5 cm, for which he undergoes
stereotactic brain radiation
 Patient
presents to oncology office to decide
about treatment options for his cancer
 Patient
has a supportive wife and daughter;
he still plays golf once a week and bridge
with his friends on Wednesday nights
Incidence of NSCLC in the US
by Age at Diagnosis
Langer et al, 2010; SEER Data 1975-2002.
Mr. PD: Treatment Considerations

Chemotherapy has survival advantage over best
supportive care for the fit elderly

Patient would like to maintain ability to play golf
and bridge and spend time with grandchildren

Chemotherapy with platinum-based doublet is
an option for him

What can we give him that can maintain quality
of life and yet give him chance for increased
survival? Family wants him to pursue treatment.
NCCN, 2013.
IFCT-0501: Weekly PC Doublet Superior to
Single-Agent Chemotherapy
Overall survival (ITT)
MST = median survival time.
Quoix et al, 2011.
Which Treatment Regimen to Use?
 Toxicity
was similar in both arms
 Weekly
paclitaxel/carboplatin a reasonable
treatment option for elderly patients based on
2011 trial data
 More
recent study examined weekly
nab-paclitaxel/carboplatin versus
paclitaxel/carboplatin every 3 weeks
Quoix et al, 2011.
nab-Paclitaxel in Elderly Patients
• In elderly patients, a nonsignificant trend toward improved PFS (8.0 vs 6.8 months;
HR=0.687; 95% CI:0.420-1.123; P=0.134)
• A significant improvement in OS was observed with nab-PC vs sb-PC
• In patients <70 years of age, there was no difference in PFS or OS
Kaplan-Meier Curve of Overall Survival in Patients ≥70 Years
Probability of Survival
1.00
nab-PC (n=74)
sb-PC (n=82)
0.75
19.9 months
0.50
10.4 months
0.25
HR=0.583
95% Cl:0.388-0.875
P=0.009
0.00
0
3
6
9
12
Months
sb-PC = subcutaneous paclitaxel.
Socinski et al, 2013.
15
18
21
24
Populations
That Benefited
Most
• North America
• Elderly (age ≥70)
• Squamous histology
Socinski et al, 2013.
Neuropathy in Elderly Patients in
nab-Paclitaxel Study
FACT-Taxane Results in Patients ≥70 Years
6
Peripheral Neuropathy
4.99
5
4
3
1.86
2
1
0
BL C2
Socinski et al, 2013.
C3
C4
C5
C6
C7
C8 Final
FACT Subscore: Mean Baseline Score or Mean
Change from Baseline
FACT Subscore: Mean Baseline Score or Mean
Change From Baseline
nab-PC
3
sb-PC
Pain in Hands/Feet
2.19
2.5
2
1.5
0.70
1
0.5
0
-0.5
BL
C2
C3
C4
C5
C6
C7
C8
Final
Management of CIPN

Complicating comorbidities, are they under control?

Assessment: FACT-Taxane? DTRs? Vibration
testing? Neurological consult for electromyography?

Several studies evaluating agents such as
nortriptyline, amitriptyline, gabapentin, and
lamotrigine have not shown a benefit, though these
agents are often used in clinical practice

Duloxetine is the only agent shown to diminish CIPN
in a phase III trial
DTRs = deep tendon reflexes; CIPN = chemotherapy-induced peripheral neuropathy.
Eaby-Sandy, 2013.
Patient Education Challenges
 Explaining
targeted therapy versus
chemotherapy
 Adherence
to oral therapies
– Cost, Medicare “donut hole”
– Over-adherence vs under-adherence
– Increased clinic visits
– Phone call support
– Logging, pillboxes
– Education on side-effect management
Neuss et al, 2013.
Key Takeaways
 Treatment
strategies for advanced NSCLC
continue to evolve: maintenance, more
aggressive treatment for elderly patients
 Toxicity
profiles can vary significantly
depending on selected agent(s)
 Oncology
nurses play an important role in
monitoring for and managing toxicities, as
well as providing patient education
References
Alimta® (pemetrexed) prescribing information (2012). Eli Lilly and Company.
American Cancer Society (2013). American Cancer Society: Cancer facts & figures 2013. Atlanta.
Avastin® (bevacizumab) prescribing information (2013). Genentech USA, Inc.
Camidge DR, Bang YJ, Kwak EL, et al (2012). Activity and safety of crizotinib in patients with ALK-positive non-smallcell lung cancer: updated results from a phase 1 study. Lancet Oncol, 13(10):1011-1019.
Cappuzzo F, Ciuleanu T, Stelmakh L, et al (2010). Erlotinib as maintenance treatment in advanced non-small-cell lung
cancer: a multicenter, randomized, placebo-controlled phase 3 study. Lancet, 11(6):521-529.
Capuzzo F, Marchetti A, Skokan M, et al (2009). Increased MET gene copy number negatively affects survival of
surgically resected non-small-cell lung cancer patients. J Clin Oncol, 27(10):1667-1674.
Ciuleanu T, Brodowicz T, Zielinski C, et al (2009). Maintenance pemetrexed plus best supportive care versus placebo
plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet,
374(9699):1432-1440.
Eaby-Sandy B (2011). Cancer Nursing: Principals and Practice. Jones and Bartlett Publishers. Sudbury,
Massachusetts.
Eaby-Sandy B, Ko A, Renschler et al (2013). Efficacy and toxicity profile of nab-paclitaxel in patients with advanced
non-small cell lung cancer (NSCLC): nursing implications and management strategies. Poster presented at Oncology
Nursing Society 38th Congress in Washington, DC.
Erbitux® (cetuximab) prescribing information (2013). New York, NY: ImClone Systems, Inc and Princeton, NJ: BristolMyers Squibb Co.
Fukuoka M, Wu YL, Thongprasert S, et al (2011). Biomarker analyses and final overall survival results from a phase III,
randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with
advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol, 29(21):2866-2874.
References
Hirsch FR (2012). Recent advances in biomarker research in lung cancer with special reference to new targeted
therapies. Presented at: 13th International Lung Cancer Congress; July 19-22, 2012; Huntington Beach, CA.
Iressa® (gefitinib) prescribing information (2010). Wilmington, DE: AstraZeneca Pharmaceuticals LP.
Lacouture ME, Anadkat MJ, Bensadoun RJ, et al (2011). Clinical practice guidelines for the prevention and treatment of
EGFR inhibitor-associated dermatologic toxicities. Support Care Cancer, 19(8):1079-1095.
Lacouture ME, Mitchell EP, Piperdi B, et al (2010). Skin toxicity evaluation protocol with panitumumab (STEPP), a
phase II, open-label, randomized trial evaluating the impact of a pre-Emptive Skin treatment regimen on skin toxicities
and quality of life in patients with metastatic colorectal cancer. J Clin Oncol, 28(8):1351-1357.
Langer CJ, Besse B, Gualberto A, et al (2010). The evolving role of histology in the management of advanced nonsmall cell lung cancer. J Clin Oncol, 28(36):5311-5320.
National Comprehensive Cancer Network (NCCN) (2013). Clinical practice guidelines in oncology. Non-small cell lung
cancer. V.2.2013. Available at http://www.nccn.org.
Neuss MN, Polovich M, McNiff K, et al (2013). 2013 updated American Society of Clinical Oncology/Oncology Nursing
Society chemotherapy administration safety standards including standards for the safe administration and management
of oral chemotherapy. J Oncol Practice, 9(Suppl):5S-13S.
Paz-Ares L, de Marinis F, Dediu M, et al (2012). Maintenance therapy with pemetrexed plus best supportive care
versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet
Oncol, 13(3):247-255.
References
Quoix E, Zalcman G, Oster JP, et al (2011). Carboplatin and weekly paclitaxel doublet chemotherapy compared with
monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial.
Lancet, 378(9796):1079-1088.
Rodriguez E, Lilenbaum RC (2008). New treatment strategies in patients with advanced non-small-cell lung cancer and
performance status 2. Clin Lung Cancer, 9(6):326-330.
Rosell R, Carcereny E, Gervais R, et al (2012). Erlotinib versus standard chemotherapy as first-line treatment for
European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, openlabel, randomised phase 3 trial. Lancet Oncology, 13(3):239-246.
Sandler A, Graham C, Baggstrom M, et al (2011). An open-label, multicenter, three-stage, phase II study of s-1 in
combination with cisplatin as first-line therapy for patients with advanced non-small cell lung cancer. J Thoracic Oncol,
6(8):1400-1406.
Sandler A, Gray R, Perry MC, et al (2006). Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung
cancer. N Engl J Med, 355(24):2542-2550.
Patel JD, Socinski MA, Garon EB, et al (2012). A randomized, open-label, phase III, Label, Phase III, superiority study
of pemetrexed (Pem) + carboplatin (Cb) + bevacizumab (Bev) followed by maintenance Pem + Bev versus paclitaxel
(Pac) Cb + Bev followed by maintenance Bev in patients with sage IIIB or IV non-squamous non-cmall cell lung cancer
(NS-NSCLC). Available at: http://www.thoracicsymposium.org/MeetingProgram/documents/PLPatel.pdf.
Scagliotti GV, Novello S (2003). Pemetrexed and its emerging role in the treatment of thoracic malignancies. Expert
Opin Investig Drugs, 12(5):853-863.
References
Scagliotti GV, Parikh P, von Pawel J, et al (2008). Phase III study comparing cisplatin plus gemcitabine with cisplatin
plus pemetrexed in chemotherapy-naive patients with advanced-stage nonsmall-cell lung cancer. J Clin Oncol,
20;26(21):3543-3551.
Schiller JH, Harrington D, Belani CP, et al (2002). Comparison of four chemotherapy regimens for advanced non-smallcell lung cancer. N Engl J Med, 346(2):92-98.
Socinski MA, Langer CJ, Okamoto I, et al (2013). Safety and efficacy of weekly nab ®-paclitaxel in combination with
carboplatin as first-line therapy in elderly patients with advanced non-smallvcell lung cancer. Ann Oncol, 24(2):314-321.
Tarceva® (erlotinib) [prescribing information] (2010). Melville, NY: OSI Pharmaceuticals, Inc.
Temel JS, Greer JA, Admane S, et al (2011). Longitudinal perceptions of prognosis and goals of therapy in patients
with metastatic non-small-cell lung cancer: results of a randomized study of early palliative care. J Clin Oncol.
29(17):2319-2326.
Temel JS, Greer JA, Muzikansky A, et al (2010). Early palliative care for patients with metastatic non-small cell lung
cancer. N Engl J Med, 363(8):733-742.
Vectibix® (panitumumab) prescribing information] (2013). Thousand Oaks, CA: Amgen, Inc.
Yang JC, Schuler MH, Yamamoto N, et al (2012). LUX-Lung 3: A randomized, open-label, phase III study of afatinib
versus pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung
harboring EGFR-activating mutations. J Clin Oncol, 30(18 Suppl). Abstract LBA7500.
Yang JC, Shih JY, Su WC, et al (2012). Afatinib for patients with lung adenocarcinoma and epidermal growth factor
receptor mutations (LUX-Lung 2): a phase 2 trial. Lancet Oncol, 13(5):539-548.