Evolving Nursing Management Strategies in the
Era of Tumor Histology and Biomarker-Driven
Treatment Selection for Advanced NSCLC
Beth Eaby-Sandy, MSN, CRNP, OCN®
Nurse Practitioner
Abramson Cancer Center
Disclosure of Conflicts of Interest
Beth Eaby-Sandy, MSN, CRNP, OCN® discloses the
following relationships:
– Clovis (advisory board)
– Astra Zeneca (advisory board)
– Amgen (speakers’ bureau)
– Merck (speakers’ bureau)
– Eisai (speakers’ bureau)
– Celgene (speakers’ bureau)
Learning Objectives

Explain the role of tumor histology and molecular biomarkers in treatment
planning for advanced NSCLC

Distinguish novel NSCLC therapies available for first-line therapy,
maintenance therapy, and the treatment of elderly patients

Apply NSCLC supportive care plans based on shared goal setting,
patient health status, periodic clinical assessment, and symptom
management
NSCLC = non-small cell lung cancer.
NSCLC: Scope of the Problem
Estimated New Cancer Cases in 2015
1. Prostate: 220,800 (26%)
2. Lung/Bronchus: 115,610 (13%)
3. Colon/Rectum: 69,090 (8%)
1. Breast: 231,840 (29%)
2. Lung/Bronchus: 105,590 (13%)
3. Colon/Rectum: 63,610 (8%)
ACS, 2015.
NSCLC: Scope of the Problem
Estimated New Cancer Deaths in 2015
1. Prostate: 27,540 (9%)
2. Lung/Bronchus: 86,380 (28%)
3. Colon/Rectum: 26,100 (8%)
1. Breast: 40,290 (15%)
2. Lung/Bronchus: 71,660 (26%)
3. Colon/Rectum: 23,600 (9%)
PERSPECTIVE (Deaths)
Lung/Bronchus = 158,040 (27%)
Breast + Prostate + Colon/Rectum = 117,970 (20%)
ACS, 2015.
Lung Cancer Stages and Survival
NCI, 2015.
NSCLC: Breakdown by Subtype

Adenocarcinoma (44%)
- Most common type of
NSCLC
- Most common type in
nonsmokers

Large cell carcinoma (3%)

Other (23%)

Squamous (26%)
– Usually more centralized
– More frequently associated with
significant cough and hemoptysis
Houston et al, 2014.
NSCLC: Molecular Biomarkers

Most commonly found in adenocarcinoma, rare
in squamous cell carcinoma
 Consider testing in squamous cell for never
smokers or in mixed adenocarcinoma and
squamous
 Three most common mutations in NSCLC:
– KRAS mutation
– EGFR mutation
– EML4-ALK gene translocation

EGFR and EML4-ALK most common in patients
with never/minimal smoking history
Hirsch, 2012; NCCN, 2015b.
Molecular Abnormalities in NSCLC
With Current Implications
EGFR




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 almost never coexists with EGFR, HER2, or KRAS mutations,
indicating it is a distinct disease subtype
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 or afatinib
 Mutations: highest incidence in never smokers, adenocarcinoma, women, and
patients with Asian ethnicity
25% of North American population
Associated with smoking and resistance to tyrosine kinase inhibitors (TKIs)
There are different types of KRAS mutations
Therapy with drugs other than erlotinib should be considered first
NCCN, 2015b; Langer et al, 2010.
Molecular Abnormalities of Interest
ROS 1 rearrangement




T790M
 EGFR resistance mutation
 >60% of patients develop it after treatment
 Drugs in clinical trials: CO-1686, AZD9291
BRAF
 4% NSCLC
 Most common is V600E
 Decreased PFS from platinum-based
chemotherapy
 Drugs in clinical trials: dabrafenib
RET
 1-2% NSCLC
 Highly associated with young, never smokers
 Drugs in clinical trials: vandetanib, cabozantinib
1-2% of NSCLC
Detected via FISH test
Sensitive to crizotinib
Usually in younger, never smokers
FISH = fluorescence in situ hybridization; PFS = progression-free survival.
Bergethon et al, 2012; Cardarella et al, 2013; Tsuta et al, 2014.
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
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 issues (eg, hair loss)
– Advanced directives
 Demographics
 Social
support
– Involve social worker
– Counseling services
– Nutrition services
 Financial
issues
Supportive Care Paradigms

Both ASCO and NCCN recommend
integration of palliative care into oncology
practice

Early palliative care leads to increase in
overall survival (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
ASCO = American Society of Clinical Oncology; NCCN = National Comprehensive Cancer Network.
Temel et al, 2011; Temel et al, 2010; Smith et al, 2012; NCCN, 2015b.
Case Study 1:
First-Line Treatment
Mrs. JF: History

68-year-old woman, presented 1 month ago with pain in
her lower back

Initial management with nonsteroidal antiinflamatory drugs
somewhat helpful; however, the pain persisted and an xray 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 positron emission
tomography/computed tomography (PET/CT) revealed a
right lung mass, mediastinal lymphadenopathy, bone
metastases in the lumbar spine, and liver metastases
– X-rays are often negative
Mrs. JF: Diagnostic Evaluation

Treating physician referred the patient to a pulmonologist
for a bronchoscopy with biopsy
– Mediastinal lymph node was positive for NSCLC,
adenocarcinoma histology

Magnetic resonance imaging (MRI) scan of the brain
negative for metastatic disease

Baseline labs within normal limits

Baseline PS 1

What factors important in treatment planning?
Mrs. JF: Treatment Considerations

Molecular analysis: Do you have enough tissue?
What to test for? Which are actionable?

Smoking history?

Comorbidities?

Weight loss, hemoptysis?

Goals of care, palliative care, incurable illness:
Talk to your patient about these important, yet
sensitive topics!
Mrs. JF: Treatment Considerations

Bronchoscopy yielded core biopsy. Tissue was sent for full
molecular analysis. Negative for EGFR, ALK, and ROS1
Patient has a 45-pack-year smoking history, currently trying to
quit
 Patient has hypertension (controlled with medication),
hypercholesterolemia, 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, 2015b.
Mrs. JF: Treatment Selection
 Cisplatin
vs. carboplatin? In US, carboplatin
is often used in frontline therapy
 Which
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
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
q3w
Importance of Histology
Overall Survival Improved With Pemetrexed/Cisplatin vs.
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)
E4599 Trial: Bevacizumab + PC vs. PC Alone in
First-Line Nonsquamous NSCLC
1-year survival:
51% vs. 44%
2-year survival:
23% vs. 15%
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
Induction Phase
q21d, 4 cycles
Inclusion:
− No prior systemic therapy
for lung cancer
− PS 0/1
− Stage IIIB-IV
nonsquamous NSCLC
− Stable treated brain
metastasized
Pemetrexed
+ Carboplatin
+ Bevacizumab
R
1:1
Exclusion:
− Peripheral neuropathy
≥grade 1
− Uncontrolled pleural
effusions
PD = progressive disease.
Patel et al, 2012.
Maintenance Phase
q21d until PD
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?
Platinum-Based Chemotherapy: CINV



Cisplatin is highly emetogenic; carboplatin is moderately
emetogenic
Following guidelines may be important in future for
reimbursement
Additional risk factors beyond the drug that contribute to
CINV:
–
–
–
–
–
–
–
Female
Younger age (<50 years)
H/O low alcohol intake, <1.5 oz/d
H/O motion sickness
H/O morning sickness with pregnancy
H/O prior CINV
Anxiety
CINV = chemotherapy-induced nausea and vomiting; H/O = history of.
Navari, 2003; Schwartzberg, 2007; Aapro et al, 2012.
Prophylaxis for High Emetic Risk
Netupitant-Based
Regimen
Aprepitant-Based Regimen
Day 1



Days 2,3,4


NCCN, 2015a.
Either:
- Aprepitant 125 mg PO
once
- Fosaprepitant 150 mg IV
once
5-HT3 antagonist
Dexamethasone 12 mg PO/IV
once

If aprepitant given Day 1:
– Aprepitant 80 mg PO daily
Days 2,3
– Dexamethasone 8 mg
PO/IV daily Days 2,3,4
If fosaprepitant IV given Day 1:
– No further aprepitant
needed Days 2,3
– Dexamethasone 8 mg
PO/IV once Day 2 then
8 mg PO/IV BID Days 3,4


Olanzapine-Based
Regimen
Netupitant 300
mg/palonesetron 0.5
mg PO once
Dexamethasone
12 mg PO/IV once

Dexamethasone
8 mg PO/IV daily



Olanzapine
10 mg PO
Palonosetron
0.25 IV once
Dexamethasone
20 mg IV once
Olanzapine 10 mg
PO daily
Prophylaxis for Moderate Emetic Risk
Serotonin (5-HT3) AntagonistBased Regimen
Day 1



Days 2,3
aAprepitant

Netupitant-Based
Regimen
5-HT3 antagonist (palonosetron
0.25 mg IV once preferred)
Dexamethasone 12 mg PO/IV
once
± Aprepitant 125 mg PO once or
fosaprepitant 150 mg IV oncea

Either:
– 5-HT3 antagonist
– Dexamethasone
8 mg PO/IV
– If aprepitant Day 1:
aprepitanta 80 mg PO daily
± dexamethasone 8 mg
PO/IV
– If fosaprepitant Day 1: ±
Dexamethasone 8 mg
PO/IV daily


Olanzapine-Based
Regimen
Netupitant 300
mg/palonosetron
0.5 mg PO
Dexamethasone
12 mg PO/IV

± Dexamethasone
8 mg PO/IV daily

should be added for select patients receiving moderate emetogenic chemotherapy with
additional risk factors or who have failed prior 5-HT3 and steroids.
NCCN, 2015a.


Olanzapine 10 mg
PO once
Palonosetron
0.25 mg IV once
Dexamethasone
20 mg IV once
Olanzapine 10 mg
PO daily
Case Study 1 Continued:
Maintenance Therapy
Mrs. JF: Post-Induction

After treatment with six cycles of
pemetrexed/carboplatin/bevacizumab, her tumor is
stable

Experienced a 20% reduction in tumor volume after two
cycles, and disease has not worsened since

Overall she has tolerated the regimen with minimal
toxicity

Her options are now:
– Stop chemotherapy, best supportive care, re-scan in 2 months
– Continue with maintenance chemotherapy
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 four to six cycles does not
improve survival, just increases toxicity

However, several drugs have shown
improvement in PFS in the maintenance setting
NCCN, 2015b.
Maintenance Pemetrexed
Both studies showed improvement in OS when either switching to or continuing
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)
 Co-primary 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
Cappuzzo et al, 2010.
3
6
9
12
15
18
21
Time (months)
24
27
30
33
36
Incidence and Severity of Rash
Drug
All Rash Incidence
Cetuximab
89%
(70% in FLEX trial)
Grade 3/4
Incidence
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)
Recommended
Not Recommended
Level of
Evidence
Recommendation
Grades
Comments
Doxycycline is
preferred in patients
with renal
impairment.
Minocycline is less
photosensitizing.
Topical
• Hydrocortisone 1%
cream with moisturizer
and sunscreen BID
• Pimecrolimus 1%
cream
• Tazarotene 0.05%
cream
• Sunscreen as single
agent
IIa
C
Systemic
• Minocycline 100 mg/d
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/d
• 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. 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®
Maintenance Treatment Conclusions

Again, there are options, just like in first-line
chemotherapy

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 2:
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 revealed 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 clinic 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
Median age at diagnosis: 70
Langer et al, 2010; SEER data, 2008-2012.
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, 2015b.
IFCT-0501: Weekly PC Doublet Superior to
Single-Agent Chemotherapy
Overall survival (ITT)
MST = median survival time.
Quoix et al, 2011.
nab-Paclitaxel in Elderly Patients
 In elderly patients, a non-significant 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 = solvent-based.
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? Deep tendon reflexes?
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
CIPN = chemotherapy-induced peripheral neuropathy.
Eaby-Sandy, 2013.
Newest Class of Agents in NSCLC: PD1 Inhibitors

Well tolerated, could be used in elderly given favorable
safety profile
 Nivolumab is only approved agent, second line after
failure of chemotherapy
 Tumors evade immune attack by having the PD-1 ligand
bind to T-cells and inactivate them against the tumor
 PD-1 inhibitors stop this process, thus leaving the tumor
vulnerable to attack
 Other drugs under investigation: pembrolizumab,
MPDL3280A (PD-L1), MEDI4736 (PD-L1), ipilumumab
(CTLA-4), tremelumumab (CTLA-4)
Cancer Research Institute, 2014.
Nivolumab vs. Docetaxel:
Overall Survival
100
Nivolumab
n=135
Docetaxel
n=137
mOS mo,
(95% CI)
9.2
(7.3, 13.3)
6.0
(5.1, 7.3)
# events
86
113
90
80
70
60
OS (%)
1-yr OS rate = 42%
HR=0.59 (95% CI: 0.44, 0.79), P=0.00025
50
40
Nivolumab
30
20
Docetaxel
10
1-yr OS rate = 24%
0
0
3
6
9
12
15
18
21
24
Time (months)
Number of Patients at Risk
Nivolumab
135
113
86
69
52
31
15
7
0
Docetaxel
137
103
68
45
30
14
7
2
0
Symbols represent censored observations.
Spigel et al, 2015.
Treatment-Related Select AEs
Nivolumab
n=131
Any Grade
Grade 3/4
Any Grade
Grade 3/4
Endocrine, %
Hypothyroidism
4
4
0
0
0
0
0
0
Gastrointestinal, %
Diarrhea
Colitis
8
8
1
1
0
1
20
20
0
2
2
0
Hepatic,a %
ALT increased
AST increased
2
2
2
0
0
0
2
1
1
1
1
1
Pulmonary, %
Pneumonitis
Lung infiltration
Interstitial lung disease
5
5
1
0
1
1
0
0
1b
0
0
1b
0
0
0
0
Renal,c %
Blood creatinine increased
Tubulointerstitial nephritis
3
3
1
1
0
1
2
2
0
0
0
0
Skin,d %
9
0
9
2
Hypersensitivity/Infusion reaction, %
Hypersensitivity
Infusion-related reaction
1
0
1
0
0
0
2
2
1
1
1
0
 Select
aNo
Docetaxel
n=129
AEs: AEs with potential immunologic etiology that require frequent monitoring/intervention
cases of increased bilirubin occurred in the nivolumab arm. bGrade 5 event. cNo cases of renal failure were reported in the
nivolumab arm. dIncludes rash, pruritus, erythema, maculopapular rash, skin exfoliation, urticaria, and hand-foot syndrome. Spigel et al,
2015.
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
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