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 ProblemEstimated 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.

PERSPECTIVELung/Bronchus Deaths = 159,480Breast, Prostate, Colon/Rectum, and Pancreatic Deaths = 158,630

NSCLC: Scope of the ProblemEstimated 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.

Lung Cancer Stages and Survival

0

20

40

60

2003-2009, All Races, Both Sexes

Stage Distribution (%) 5-Year Relative Survival (%)

Stage

Pe

rce

nt

SEER Data, 2003-2009.

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 innonsmokers

– 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 BiomarkersUnknown

KRAS

EGFR

ALK

RET

MET

PI3K

BRAF

HER2

PDGFR

VEGFR

FGFR1

AKT1

MEK1

ROS1

5%

25%

15%

33%

5%

3% 3% 3%

2%

1%

Hirsch, 2012.

NCCN, 2013; Langer et al, 2010.

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 • 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

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

Molecular Abnormalities in NSCLC With Current Implications

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 monthsPFS = 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%

q3wAUC=6 mg/mL/min D1225 mg/m2/3h D1

CarboplatinPaclitaxel

q3w75 mg/m2 D175 mg/m2 D1

CisplatinDocetaxel

q4w100 mg/m2 D11 g/m2 D1,8,15

CisplatinGemcitabine

q3w75 mg/m2 D2135 mg/m2/24h

CisplatinPaclitaxelR

ANDOMIZE

AUC = area under the curve.Schiller et al, 2002.

Similar efficacy for all doubletsSimilar efficacy for all doublets

Importance of Histology

Overall Survival for Pemetrexed/Cisplatin VersusGemcitabine/Cisplatin in First-Line Adenocarcinoma Patients

CI = confidence interval.Scagliotti et al, 2008; Scagliotti & Novello, 2003.

Median OS (months)(95% CI)

12.6(10.7-13.6)

10.9(10.2-11.9)

Pemetrexed/Cisplatin

(n=436)

Gemcitabine/Cisplatin

(n=411)

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

Median OS with Bevacizumab + PC was 12.3 months vs 10.3 months for PC

alone (P=0.013)

PC = paclitaxel + carboplatin.Sandler et al, 2006; Sandler et al, 2011.

1-year survival: 51% vs 44%

2-year survival:23% vs 15%

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 Maintenance Phase q21d, 4 cycles q21d until PD

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

Pemetrexed+ Carboplatin

+ BevacizumabPemetrexed

+ Bevacizumab

Paclitaxel+ Carboplatin

+ BevacizumabBevacizumab

450 Patients Each

q21d= every 21 days; PD = progressive disease.Patel et al, 2012.

R1:1

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

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)

Bev 15 mg/kg IVq3w until disease

progression or unacceptable

toxicity

Stratified by• Disease stage• Degree of weight

loss• Prior radiotherapy• Measurable disease

Primaryend point

OS

Secondaryend points

Response rate, PFS, toxicity

q3w = every 3 weeks; IV = intravenously. Sandler et al, 2006.

First-line treatment of patients with stage IIIB and

malignant pleural effusion, stage IV,

or recurrent NSCLC (N=878)

Continued until progression or unacceptable 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

Induction Phase Maintenance Phase q21d, 4 cycles q21d until PD

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

Pemetrexed+ Carboplatin

+ BevacizumabPemetrexed

+ Bevacizumab

Paclitaxel+ Carboplatin

+ BevacizumabBevacizumab

450 Patients Each

Patel et al, 2012.

R1:1

SATURN Trial: Erlotinib Maintenance

IHC = immunohistochemistry.Cappuzzo et al, 2010.

PD

PD

Mandatory tumor sampling

4 cycles of first-line

platinum-based doublet

Chemotherapy-naive, advanced NSCLC

N=1,949

Non-PDn=889

Erlotinib150 mg/d

n=438

Placebon=451

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

SATURN Trial: Erlotinib Maintenance

0 3 6 9 12 15 18 21 24 27 30 33 36

12.0 monthsmedian OS

11.0 monthsmedian OS

OS rates in the SATURN ITT population at milestone

19% reduction in risk of death

HR = hazard ratio.Cappuzzo et al, 2010.

Time (months)

Ove

rall

Su

rviv

al P

rob

abil

ity

1.0

0.8

0.6

0.4

0.2

0

Erlotinib (n=438)

Placebo (n=451)

OS in a broad ITT population

HR=0.81 95% CI:0.70-0.95; P=0.0088

Median 12.0 months with erlotinib vs 11.0 months with placebo

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 profiles, how do they differ? Current approved EGFR tyrosine kinase

inhibitors: gefitinib (no longer approved in US), erlotinib, and afatinib

EURTAC TrialFirst-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

Pro

gre

ssio

n-F

ree

Su

rviv

al (

pro

bab

ilit

y)1.0

0.8

0.6

0.4

0.2

0.0

Number at riskAfatinib 230 180 151 120 77 50 31 10 3 0Cis/Pem 115 72 41 21 11 7 3 2 0 0

Progression-Free Survival (months)

0 3 6 9 12 15 18 21 24 27

Afatinib

n=230

Cis/pem n=115

PFS event, n (%) 152 (66) 69 (60)

Median PFS (months) 11.1 6.9

HR(95% CI)

0.58 (0.43–0.78)P=0.0004

47%

22%

Yang, Schuler et al, 2012; Yang, Shih et al, 2012.

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 panitumumab-containing 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 andTreatment 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 weeklynab-paclitaxel/carboplatin versus paclitaxel/carboplatin every 3 weeks

Quoix et al, 2011.

0.75

Pro

bab

ilit

y o

f S

urv

ival

0.50

0.00

30

95% Cl:0.388-0.875HR=0.583

10.4 months

19.9 months

P=0.009

96 15 18 21 2412

0.25

1.00 nab-PC (n=74)

sb-PC (n=82)

Kaplan-Meier Curve of Overall Survival in Patients ≥70 Years

• 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

nab-Paclitaxel in Elderly Patients

sb-PC = subcutaneous paclitaxel.Socinski et al, 2013.

Months

Populations That Benefited Most

• North America

• Elderly (age ≥70)

• Squamous histology

Socinski et al, 2013.

nab-PC sb-PC

Series1

0

1

2

3

4

5

6

1.86

4.99

C2BL

FA

CT

Su

bs

co

re:

Me

an

Ba

se

lin

e S

co

re o

r M

ea

n

Ch

an

ge

Fro

m B

as

eli

ne

C3 C4 C5 C6 C7 C8 Final

Peripheral Neuropathy

Series1

0

0.5

1

1.5

2

2.5

0.70

2.19

C2BL C3 C4 C5 C6 C7 C8 Final

Pain in Hands/Feet

FA

CT

Su

bs

co

re:

Me

an

Ba

se

lin

e S

co

re o

r M

ea

n

Ch

an

ge

fro

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as

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ne

FACT-Taxane Results in Patients ≥70 Years

Socinski et al, 2013.

Neuropathy in Elderly Patients in nab-Paclitaxel Study

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 managementNeuss 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-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol, 13(10):1011-1019.

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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.

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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 non-small 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 non-squamous 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,

open-label, 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

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