handout bw updated 2.21 bw updated 2.21.17.pdf · cec 2017 2 nsclc: an overview 85% of lung cancer...

CEC 20171

Learning Objectives

1. Outline the molecular targets of lung cancer tumor cells and how these mutations can help direct personalized treatments.2. Examine the types of novel targeted therapies used in advanced non‐small cell lung cancer (NSCLC). 3. Evaluate safety and adherence issues involved in delivering targeted therapies.4. Using an evidence‐based approach, describe how the oncology nurse can improve care using targeted therapies.

Disclaimer

This slide deck in its original and unaltered format is for educational purposes and is current as of the date of presentation. The content and views presented in this educational activity are those of the authors/presenters and do not necessarily reflect those of Creative Educational Concepts, Inc. or the supporter.

These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off‐label uses of approved products. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or employing any therapies or strategies described in this educational activity.

CEC 20172

NSCLC: AN OVERVIEW

85% of lung cancer cases

Associated with smoking ornon‐smoking history

Moderate sensitivity to radiation

Low sensitivity to conventional chemotherapy

50% of patients present in the metastatic setting Median overall survival <1

year

Cough

Most common presenting symptom

Dyspnea

Chest pain

Hoarseness

Hemoptysis

Weight loss

Epidemiology Signs and Symptoms

Beckles MA, et al. Chest. 2003;Molina RJ, et al. Mayo Clin Proc. 2008; Cetin K, et al. Clin Epidemiol. 2011.

NSCLC Overview

CEC 20173

NSCLC Overview

Adenocarcinoma

Most common histology

40% of all lung cancer diagnoses

Indolent growth

Squamous Cell Carcinoma


Usually linked to history of smoking

Indolent growth

Large Cell Carcinoma


Rapid growth

Wahbah M, et al. Ann Diagn Pathol. 2007; http://www.cancer.gov/types/lung/hp/non‐small‐cell‐lung‐treatment‐pdq#section/_359.

Adenocarcinoma40%

NSCLC MutationsAdenocarcinoma Histology

Adapted from Chia PL, et al. Clin Epidemiol. 2014.

CEC 20174

EGFR MUTANT NSCLC

HER Family of Receptors

Gespach C, et al. Clin Cancer Res. 2012. Reprinted with permission ©2012 Copyright Clearance Center. All rights reserved.

CEC 20175

HER Family of Receptors

Gespach C, et al. Clin Cancer Res. 2012. Reprinted with permission ©2012 Copyright Clearance Center. All rights reserved.

EGFR Downstream Effects

Harari P, et al. Endocr Relat Cancer. 2004. Reprinted with permission ©2004 Copyright Clearance Center. All rights reserved.

CEC 20176

Mutations in EGFR in NSCLC

Exon 19 deletion

Exon 21 L858R substitution

Exon 18 deletion

Exon 20 insertion

Adapted from Riely GJ, et al. Clin Cancer Res. 2006.

G719A/S

LREAdeletion

L861XL858R

Exon 18 Exon 19 Exon 20 Exon 21P α‐C A

Mechanism of EGFR Resistance

T790M substitution

Induces steric hindrance

EGFR TKI binding efficacy compromised

Cataldo VD, et al. N Engl J Med. 2011. Reprinted with permission ©2011 Massachusetts Medical Society. All rights reserved.

CEC 20177

Mechanism of EGFR Resistance

Yu H, et al. Clin Cancer Res. 2013.

Molecular Testing in NSCLC

National Comprehensive Cancer Network1

“The NCCN NSCLC Guidelines Panel strongly advises broader molecular profiling with the goal of identifying rare driver mutations for which effective drugs may already be available, or to appropriately counsel patients regarding the availability of clinical trials. Broad molecular profiling is a key component of the improvement of care of patients with NSCLC.”

CAP/IASLC/AMP2

Guidelines recommend EGFR and ALK mutation testing before treatment with EGFR TKIs or ALK inhibitors in all patients with lung adenocarcinoma or mixed lung cancer at the time of diagnosis or recurrence, regardless of the clinical characteristics of the patient.

1https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf; 2Leighl NB, et al. J Clin Oncol. 2014.

CEC 20178

Detecting T790M with cfDNA

Cells release small fragments of cell‐free plasma DNA (cfDNA) into circulation by multiple mechanisms

Cell‐free DNA (cfDNA) includes normal and circulating tumor DNA (ctDNA)

Size: Average 180‐200 base pairs

Half‐life: ~2 hours

Diaz LA Jr, et al. J Clin Oncol. 2014. Reprinted with permission ©2014 American Society of Clinical Oncology. All rights reserved.

Siravegna G, Bardelli A. Genome Biology. 2014.

Leon et al reported increased concentrations of cfDNA in cancer patients; Cancer Res 1977

cfDNA discovery by Mandel and Metais in 1948

RAS mutations were detected in the plasma of pancreatic cancer and leukemia patients. Sorenson et al CEBP 1994; Vasioukhin et al BJH 1994

Stroun et al (Univ. Geneva) described possible mechanisms of cfDNA release. Liquid biopsy suggested.

Microsatellite instability was described in cfDNA of cancer patients. Nowrouz et al & Chen X et al Nat Med 1996

Multiple ctDNA associated alterations in oncogenes were detected in many different tumor types.

Monitoring tumor by serial ctDNA descried in mCRC harboring an APC mutation. Diehl et al Nat Med 2008

Detection of acquired resistance using ctDNA described through detection of EGFR T790M mutation in NSCLC receiving anti‐EGFRKuang et al Clin Cancer Res 2009

Tumor evolution to acquire resistance described in serial ctDNA monitoring of CRC. Diaz et al Nature 2012

ctDNAwhole genome sequencing used to describe acquired resistance and evolution of resistant subclones in breast cancer. Murtaza et al Nature 2013

1948

1977

1994

1997‐2007

2009

2013

1989

1996

2008

2012

CEC 20179


EGFR T790M resistance mutation typically found by tissue biopsy, however, tissue biopsy:

May present risks

May delay therapy

May not be feasible

Non‐invasive blood test may be preferred for detecting T790M mutation in cfDNA


Retrospective review by Oxnard GR, et al. 2016:

70% sensitive in the detection of T790M

Similar ORR and PFS with tumor biopsy‐proven T790M

30% false negative rate Verify with tumor biopsy in cfDNAnegative patients

ENSURE Phase III trial by Wu YL, et al. 2015:

Lead to the first FDA approved liquid biopsy test, a companion diagnostic test for erlotinib. 214 patients who had plasma molecular testing:

Specificity: 76.7%

Sensitivity: 98.2%

In September of 2016, the liquid biopsy test was also approved for osimertinib.

Oxnard GR, et al. J Clin Oncol. 2016; Wu YL, et al. Ann Oncol. 2015; http://www.accessdata.fda.gov/cdrh_docs/pdf12/P120019S007c.pdf;

http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm504540.htm.

CEC 201710

Liquid Biopsy

Pros

Non‐invasive

Results back in ~2 weeks

Specificity is high

Addresses heterogeneity of tumor and metastatic sites

Helpful when there isn’t sufficient tissue or when tissue biopsy cannot be performed

Cons

Cost

Must collect and send to liquid biopsy company

Sensitivity not as high as with tissue

Not as accurate in early disease

Certain chronic conditions may also increase cfDNAlevels

Sholl LM, et al. Arch Pathol Lab Med. 2016; Jiang T, et al. Lung Cancer. 2015; Newman AM, et al. Nat Med. 2014.

TARGETED THERAPIES FOR EGFR MUTANT ADVANCED NSCLC

CEC 201711

The EGFR Mutant Patient

10% Western culture/50% Asian

Never smoker

Women

Adenocarcinoma

Non‐mucinous

http://www.nccn.org/professionals/physician_gls/pdf/lung_screening.pdf.

Timeline of Discovery

Adapted from Strebhardt K, Ullrich A. Nat Rev Cancer. 2008; http://www.centerwatch.com/drug‐information/fda‐approved‐drugs/therapeutic‐area/12/oncology.

1897

Magic Bullet Concept

1946

Nitrogen Mustard

1948Folic Acid Antagonists

Anti‐metabolitesAnalogues of DNA

1984

EGFR

1987

Erbb2 gene amplification

1997

Rituximab

1998

Trastuzumab

2001

AlemtuzumabImatinib

2003

Gefitinib

2004BevacizumabErlotinibCetuximab

2005

Sorafenib

2006SunitinibDasatinib

Panitumumab

2007

Lapatinib

2009

Ofatumumab

2011CrizotinibIpilimumabVandetanib

2012RegorafenibCabozantinibBosutinib

2013

Afatinib

2016

Osimertinib

CEC 201712

Trial Treatment Mutations PFS ORR (%)

NEJ002N=114

Gefitinibvs Carbo/Pac

EGFRm (absence of T790M)

10.8 months vs 5.4 months P<.001

74 vs 31P<.001

WJTOG3405N=51

Gefitinibvs Cis/Doc

Del19 & L858R8.4 months vs 5.3

months P<.0001

62 vs 32P<.0001

IPASSN=132

Gefitinibvs Carbo/Pac

No EGFR status required

9.5 months vs 6.3 months P<.001

71 vs 47P<.001

EURTACN=86

Erlotinibvs standard chemo*

Del19 or L858R9.7 months vs 5.2

months P<.0001

58 vs 15P value not reported

OPTIMALN=82

Erlotinibvs standard chemo**

Del19 or L858R13.1 months vs 4.6

monthsP<.0001

83 vs 36P<.0001

First‐line EGFR TKIs vs Chemotherapy

Sebastian M, et al. Eur Respir Rev. 2014.

N=Patients treated with TKI*Cis/Doc, Cis/Gem, Carbo/Doc, Carbo/Gem**Carbo/Gem

First‐line EGFR TKIs vs Chemotherapy

Trial Treatment Mutations PFS ORR (%)

ENSUREN=110

Erlotinib vs Cis/Gem Del19 or L858R

11 months vs 5.6 months†P<.0001

63 vs 34†P=.0001

11 months vs 5.5 monthsP<.0001

LUX‐LUNG 3N=230

Afatinib vs Cis/PemEGFR mutation

positive

11.1 months vs 6.9 months†P=.001

56 vs 23†P=.001

11.1 months vs 6.7 monthsP=.001

69 vs 44P=.001

LUX‐LUNG 6N=242

Afatinib vs Cis/GemEGFR mutation

positive

11 months vs 5.6 months†P<.0001

67 vs 23†P<.0001

13.7 months vs 5.6 monthsP<.0001

74 vs 31P value not reported

Sebastian M, et al. Eur Respir Rev. 2014.

†Independently assessedN=Patients treated with TKI

CEC 201713

EGFR mutation discovered duringfirst‐line chemotherapy

Complete planned chemo‐therapy, including maintenance therapy, or interrupt, followed by erlotinib or afatinib or gefitinib

Erlotinib(category 1)orAfatinib(category 1)orGefitinib(category 1)

EGFR mutation discovered prior to first‐line chemotherapy

Decision to Treat with EGFR TherapyNCCN Guidelines Version 4.2017

Adapted from: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf.

ProgressionBrain

• Consider local therapy• Osimertinib (if T790M+)(category 1)

OR • Continue erlotinib orafatinib or gefitinib

Osimertinib (category 1), if not previously given

Sensitizing EGFR mutation positive

T790M testing if progression*

Asymptomatic

Symptomatic

Systemic

Isolatedlesion

Multiplelesions

SUBSEQUENT THERAPY FIRST‐LINE THERAPY

*If tissue biopsy is not feasible, plasma biopsy should be considered. Consider reflex to tissue‐based testing, if plasma test is negative for the T790M mutation.NOTE: All recommendations are category 2A unless otherwise indicated

T790M+

T790M‐See first‐line therapy options for adenocarcinoma and squamous cell carcinoma or PD‐L1expression positive (>50%), see first‐line therapy

• Consider local therapy• Osimertinib (if T790M+)(category 1)

OR • Continue erlotinib orafatinib or gefitinib

• Consider local therapy• Continue erlotinib orafatinib or gefitinib

OR

EGFR Tyrosine Kinase Inhibitors

Gefitinib (1st Generation) Erlotinib (1st Generation) Afatinib (2nd Generation)

MOA Reversible inhibition of EGFRHighly selective irreversible blocker of

EGFR, HER2, and HER4

Indications/Dosage

Metastatic NSCLC with EGFR exon 19 deletion or exon 21 L858R substitution mutations (first‐line): 250 mg PO once daily



Dose Adjustments

• Renal: No recommendation; minimal renal excretion

• Hepatic:Withhold in worsening liver dysfunction; discontinue in severe hepatic impairment

• Strong CYP3A4 inducers: Increase to 500 mg PO daily

• Renal: Hold treatment for grade3/4 renal toxicity or consider discontinuation

• Hepatic: Hold or discontinue for bilirubin >3x ULN and/or transaminases >5x ULN

• Concomitant CYP3A4/CYP1A2 inhibitors or 3A4 inducers

• Concomitant smoking induces metabolism

• Renal o CrCl 15‐29 mL/min 30 mg PO

once dailyo CrCl <15 mL/min Not studied;

avoid use in CrCl <15 mL/min • Hepatic:Withhold for > grade 3

hepatic dysfunction and reduce by 10 mg upon improvement to < grade 1

FDA Prescribing Information.

CEC 201714

EGFR Tyrosine Kinase Inhibitors

Gefitinib (1st Generation) Erlotinib (1st Generation) Afatinib (2nd Generation)

Adverse Effects

• Common: Acneiform rash, diarrhea, fatigue, anorexia, paronychia

• Serious: GI perforation, bleeding events, cardiac events, severe skin reactions, hepatotoxicity, pulmonary toxicity

• Emetic Potential: Minimal (<10%)

• Common: Acneiform rash, diarrhea, fatigue, anorexia, cough, dyspnea, paronychia

• Serious: GI perforation, bleeding events, cardiac events, severe skin reactions, hepatotoxicity, pulmonary toxicity


• Common: Acneiform rash, paronychia, pruritus, diarrhea, decreased appetite, stomatitis

• Serious: Cardiovascular toxicity (decreased LVEF), cutaneous reactions, diarrhea/stomatitis, hepatotoxicity, keratitis, pulmonary toxicity


Drug/Food Interactions

• Substrate of BCRP, CYP2D6, CYP3A4

• Inhibits BCRP, CYP2C19, CYP2D6

• Administer with or without food

• Substrate of CYP1A2 (minor) and CYP3A4 (major)

• Administer 1 hour before or 2 hours after a meal (emptystomach)

• Substrate & inhibitor of BCRP and P‐gp

• Administer 1 hour before or 2‐3 hours after a meal (emptystomach)

MonitoringEGFR mutation status; LFTs and renal function, electrolytes, other signs of toxicity

EGFR mutation status; LFTs and renal function, electrolytes, other signs of toxicity

EGFR mutation status; LFTs and renal function, skin toxicity, diarrhea

FDA Prescribing Information; https://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf.

Efficacy Among First‐line EGFR TKIs

CTONG0901

Erlotinib vs gefitinib in EGFR TKI naïve and EGFR TKI progressive patients with exon 19 or 21 EGFR mutations

No statistically significant difference in PFS or OS

Similar toxicity profiles

Erlotinib and gefitinib were both superior in exon 19 mutation patients in terms of ORR (62.2% vs 43.5%; P=.003) and OS (22.9 months vs 17.8 months; P=.022)

WJOG5108L

Erlotinib vs gefitinib in EGFR TKI naïve patients with EGFR mutations

No statistical difference in PFS, ORR, or OS between the two groups

Toxicities were similar among both groups

Yang J, et al. Br J Cancer. 2017; Urata Y, et al. J Clin Oncol. 2016.

CEC 201715

Efficacy Among First‐line EGFR TKIs

Paz‐Arez, L et al. Ann Oncol. 2017.

LUX‐LUNG 7

Afatinib vs gefitinib

EGFR TKI naïve patients with EGFR sensitizing mutations

Gefitinib Afatinib

Median PFS10.9 months 11 months

P=.017

TTF11.5 months 13.7 months

P=.0073

Median OS24.5 months 27.9 months

P=.258

However, there were significantly more toxicities with afatinib when compared to gefitinib

Resistance to EGFR Therapy Eventually Happens

Median PFS ‐ 10.8 vs 5.4 months

Maemondo M, et al. N Engl J Med. 2010. Reprinted with permission ©2010 Massachusetts Medical Society. All rights reserved.

CEC 201716

Third Generation EGFR Inhibitor

Osimertinib

Selective for resistant/mutant forms of EGFR over wild‐type (~200 times greater potency)

Also inhibits HER2, HER3, HER4

FDA accelerated approval in 2015

Treatment of metastatic EGFR T790M mutation‐positive NSCLC

After progression on or after EGFR TKI therapy

Dose: 80 mg once daily

Cross D, et al. Cancer Discov. 2014;FDA Prescribing Information.

Osimertinib (AZD9291) Progression‐Free Survival by T790M

Jänne PA, et al. N Engl J Med. 2015. Reprinted with permission ©2015 Massachusetts Medical Society. All rights reserved.

CEC 201717

Osimertinib vs Chemotherapy in T790M

Mok T, et al. N Engl J Med. 2017.

Intent‐to‐Treat Population Patients with CNS Metastases

No. of Patients Median PFSmo (95% CI)

Osimertinib 279 10.1 (8.3‐12.3)

Platinum‐pemetrexed

140 4.4 (4.2‐5.6)

No. of Patients

Median PFSmo (95% CI)

Osimertinib 93 8.5 (6.8‐12.3)

Platinum‐pemetrexed

51 4.2 (4.1‐5.4)

Mok T, et al – Recent phase 3 study comparing osimertinib to platinum‐pemetrexed in T790M patients who progressed while on first‐line EGFR TKI therapy.

EGFR TKI TOXICITIES

CEC 201718

96

NR

29

71

90

31

21

58

NR0

10

20

30

40

50

60

70

80

90

100

Toxicities of EGFR TKI TherapyAll Grade Adverse Events

Afatinib Erlotinib

Percentage of Patients Experiencing (%

)

54

33

23

52

17

75

12 13

3.9

52

41

Compiled from FDA Prescribing Information; current as of September 2016.

NR=Not Reported

42

17 1612

41

31

14

25

14

Toxicities of EGFR TKI TherapyAll Grade Adverse Events

Gefitinib Osimertinib

29

1417

7

47

NR NR5

NR0

10

20

30

40

50

60

70

80

90

100


)


NR=Not Reported

CEC 201719

15

NR

4

9

16

0 0

11

NR0

5

10

15

20

25

30

Toxicities of EGFR TKI Therapy>Grade 3 Adverse Events

Afatinib Erlotinib


)

6

32

9

<1

8

0 <1 <1

18

28


NR=Not Reported

31.2

2.3

0.32

NR NR 0.1 NR0

5

10

15

20

25

30

Toxicities of EGFR TKI Therapy>Grade 3 Adverse Events

Gefitinib Osimertinib


)

1 0.5 0.7 0 0.5 0 0 0 0.5


NR=Not Reported

CEC 201720

ROLE OF THE ONCOLOGY NURSE

NCI‐CTCAE Grading Guideline

http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010‐06‐14_QuickReference_5x7.pdf.

Grade 1 Grade 2 Grade 3 Grade 4 Grade 5

Mild Moderate

Severe or medically significant but not immediately life‐

threatening

Life‐threatening consequences

Death

Asymptomaticor mild symptoms;

Clinical or diagnostic observations only;

Intervention not indicated

Minimal, local or noninvasiveintervention indicated;

Limiting age‐appropriate instrumental ADL

Hospitalization or prolongation of hospitalization indicated;

Disabling; Limiting self‐

care ADL

Urgent intervention indicated

Death related to AE

Instrumental ADL – preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. Self Care ADL – bathing, dressing and undressing, feeding self, using the toilet, taking medications and not bedridden.

CEC 201721

EGFR Inhibitor Rash

EGFRs are present in follicular epithelium, sebaceous glands, and dermal capillaries, explaining the skin toxicities seen with EGFR TKIs.

Generally presents on face, scalp, chest and back

Can range from mild to severe

Hirsh V. Curr Oncol. 2011.

Grading Tools for EGFR Rash

The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI‐CTCAE) is typically used for clinical trial grading of adverse events.

The Multinational Association of Supportive Care in Cancer (MASCC) has published the EGFR Inhibitor Toxicity Tool (MESTT), “as an event‐specific grading system that can be used to standardize assessment, optimize the use of EGFR inhibitors and enable researchers to conduct more informative, controlled studies.”

http://www.mascc.org/MESTT.

CEC 201722

Grade 1 Grade 2 Grade 3 Grade 4 Grade 5

Rash acneiform*

*A disorder characterized by an eruption of papules and

pustules, typically

appearing on face, scalp, upper chest,and back

Papules and/or pustules

covering <10% BSA, which may or may not be associated with symptoms of pruritus or tenderness

Papules and/or pustules

covering 10–30% BSA,

which may or may not be associated

with symptoms of pruritus or tenderness; associated

with psychosocial

impact; limiting to

instrumental ADL

Papules and/or pustules covering >30% BSA, which may or may not be associated with symptoms of pruritus or tenderness;

limiting self‐care ADL; associated

with local superinfection,

with oral antibiotics indicated

Papules and/or pustules covering any % BSA, which may or may not be associated

with symptoms of pruritus or tenderness;

associated with extensive

superinfection, with IV antibiotics indicated; lead to life‐threatening consequences

Death


NCI‐CTCAE Rash Grading Scale

MASCC Rash Grading Scale

Lacouture ME, et al. Support Care Cancer. 2010.

Grade 1 Grade 2 Grade 3

Papulopustulareruption

(Grading individually for face, scalp, chest, or back)

1A: Papules or pustules <5 OR 1

area of erythema or edema <1 cm in size

1B: Papules or pustules <5 OR 1

area of erythema or edema <1 cm in size AND pain or pruritus

2A: Papules orpustules 6‐20 OR 2–5 areas of

erythema or edema <1 cm in size

2B: Papules or pustules 6‐20 OR 2–5 areas of

erythema or edema <1 cm in size AND pain, pruritus or

effect on emotions or functioning

3A: Papules or pustules >20 OR >5 areas of erythema or

edema <1 cm in size

3B: Papules or pustules >20 OR >5 areas of erythema or edema <1 cm in sizeAND pain or pruritus

or effect on emotions or functioning

CEC 201723

EGFR Inhibitor Rash

Can present as early as 2 weeks into treatment. Patient should be evaluated for rash weekly during the first six weeks of treatment.

An assessment of oral adherence should occur regularly throughout the entire course of treatment.

Patients should be counseled on the prevalence of rash and its link to drug efficacy.

Rash can be debilitating for patients and potentially lead to adherence issues. Therefore, prevention strategies must be discussed.


MASCC Rash Prevention andTreatment Guidelines

Recommended Not RecommendedLevel of Evidence

Recommendation Grades

Comments

Preventive

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 daily Doxycyline 100 mg BID

Tetracycline 550 mg BID IIa A

Doxycycline is preferred in patients with renal impairment. Minocycline is less photosensitizing.

Treatment

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 studyMASCC = Multinational Association of Supportive Care in Cancer

CEC 201724

Paronychia With EGFR Inhibitors

Wear comfortable shoes

Trim nails without aggressive manicuring in order to avoid micro abrasions that may lead to infection

Wear gloves while cleaning

Inflammation – topical corticosteroids or tetracycline

Excessive tissue granulation – electrocautery, silver nitrate and nail avulsion

If infection occurs, tissue must be cultured in order to guide antibiotic therapy


Schirmer Test for Dry Eye

https://medlineplus.gov/ency/imagepages/9888.htm.

Used to determine whether the eye produces enough tears to keep it moist. The test is performed by placing filter paper inside the lower lid of the eye. After a few minutes, the paper is removed and the length of the paper that has become wet is measured.

CEC 201725

Diarrhea

Most likely to occur within 4 weeks of therapy initiation.

Patient should be evaluated weekly during this time.

Important to rule out other causes (other medications, diet, etc.)

May lead to reduced adherence, nutritional deficiencies, and decreased quality of life.


NCI‐CTCAE Diarrhea Grading Scale


Grade 1 Grade 2 Grade 3 Grade 4

Diarrhea

Increase of <4 stools per day over

baseline

Increase of 4‐6 stools per day over

baseline

Increase of >7 stools per day over baseline

Incontinence Hospitalizatio

n indicated Limits self‐

care activities of daily living

Life‐threatening consequences

Urgent interventionneeded

CEC 201726

Non‐Pharmacological Strategies for Diarrhea

Diet

BRAT diet (bananas, rice, apple sauce, toast)

Remove greasy, spicy and fried foods

Fluid

3‐4 L/day to prevent dehydration

Potentially probiotics


Management of DiarrheaExample Protocol from Memorial Sloan Kettering Cancer Center

Severity (CTCAE v.4) Intervention

Grade 1in absence of nausea, vomiting, fever,

neutropenia or dehydration

Continue drug at current dose and monitor for change in severity

Initiate loperamide (4 mg x 1, then 2 mg q 4‐6 hrs)Discontinue lactose‐containing products, alcohol, supplements, caffeineDrink 8‐10 glasses of fluidEat small, frequent, light mealsConsider treatment protocol recommendations

Reassess after 12‐24 hours; if diarrhea worsen or do not improve proceed to next step

When diarrhea resolves, continue drug at same doseDiscontinue loperamide after 12 hours diarrhea‐free interval

Grade 2 in absence of nausea, vomiting, fever,

neutropenia or dehydration

If intolerable, hold drug until diarrhea resolves and monitor for change in severity

Continue loperamide 2 mg every 4‐6 hrsAdd diphenoxylate/atropine 2.5 mg every 6 hours, consider Tincture of Opium 6 mg QID

Reassess after 12‐24 hours; if reactions worsen or do not improve proceed to next step;Refer to clinic or UCC When diarrhea resolves, restart study drug at same dose and continue dietary modification

Grade 3‐4 or Grade 1‐2 with one of the following symptoms:

nausea, vomiting, fever, neutropenia or dehydration

Hold drug and monitor for change in severity

Continue loperamide 2 mg every 6 hrs and dietary/hydration recommendationsAdd diphenoxylate/atropine 2.5 mg every 6 hours, consider Tincture of Opium 6 mg QID Refer to clinic or ER for IV hydration and evaluation

If diarrhea worsens or do not improve admit to hospital for managementWhen diarrhea resolves, restart study drug at reduced dose, consider prophylactic antidiarrheal use and continue dietary modifications

CEC 201727

“Drugs don’t work

if people don’t take them.”

C. Everett Koop, Former US Surgeon General

Definitions

Adherence/Compliance

“Adherence” is preferred but both terms are imperfect, and, unfortunately, can stigmatize patients

Definitions of adherence

World Health Organization

“the extent to which a patient’s behavior corresponds with agreed recommendations from a health care provider”

International Society for Pharmacoeconomics and Outcomes Research

“the degree or extent of conformity to the recommendation about day‐to‐day treatment by the provider with respect to the timing, dosage, frequency and duration of time from the initiation to discontinuation of therapy.”

Adherence is often defined to be “taking 80% or more of a medication as prescribed”

This is an arbitrary number

Adherence is impacted by multiple factorsCramer JA, et al. Value Health. 2008;

http://www.who.int/chp/knowledge/publications/adherence_Section1.pdf.

CEC 201728

Shift to Oral Cancer Treatments

Advantages

Patient convenience

No need for IV access

Can achieve sustained drug levels

Minimal disruption in daily life

Patient preference

Disadvantages

Distances patient from provider

Changes the way patients are monitored

Safeguards for prescription or administration may be lacking

Patients have more responsibility for their own care

Adherence to Oral Chemotherapy

Reminder Triggers

Pill boxes (traditional/electronic), diaries

Event reminders (eg, take medications together, take with meals)

Cell phones/alarms

Symptom Management

Provider Support and Surveillance

Weekly phone calls

Refill reminder postcard

Notify caregiver of patient concerns

Referral to counselor

Support group

Patient assistance program

Schneider SM, et al. Semin Oncol Nurs. 2011.

CEC 201729

Role of the Oncology Nurse in Palliative Care

Oncology nurses have the responsibility to encourage planning and informed choices based on the needs and values of patients.

Oncology nurses are in a unique position to advocate for patients regarding access to and delivery of quality palliative care.

Studies have shown that cancer patients benefit from early palliative care

Temel JS, et al ‐ 151 patients with metastatic NSCLC. Those with early palliative care had a better quality of life, less depression and a longer median survival than those in the control “standard care” group.

Temel JS, et al. N Engl J Med. 2010; https://www.ons.org/advocacy‐policy/positions/practice/palliative‐care.

Future Generation EGFR Inhibitors

EGF816

NCT02108964, NCT02323126, NCT02335944, NCT02900664

ASP8273

NCT02500927, NCT02192697, NCT02674555, NCT02113813, NCT02588261

AC0010

NCT02274337, NCT02330367, NCT02448251, NCT03001609

CEC 201730

Abbreviations

AE = Adverse Event

ALK = Anaplastic lymphoma kinase

APC = Adenomatous polyposis coli gene

BID = Twice daily

BP = Base pairs

BRCP = Breast cancer resistance protein

cfDNA = Cell‐free DNA

CRC = Colorectal cancer

CrCl = Creatinine clearance

CT = Computed tomography

CTCAE v.4 = Common Terminology Criteria for Adverse Events version 4.0

ctDNA = Circulating tumor DNA

CYP = Cytochrome P450

D = Day

EGFR = Epidermal growth factor receptor

ER = Emergency room

FDA = Food and Drug Administration

GI = Gastrointestinal

HER = Human epidermal growth factor receptor

IHC = ImmunoHistoChemistry

IV = Intravenous

KRAS = Kristen Rat Sarcoma

LFTs = Liver function tests

LLL = Left lower lobe

LN = Lymph node

LVEF = Left ventricular ejection fraction

Abbreviations

mAb = Monoclonal antibody

MASCC = Multinational Association of Supportive Care in Cancer

mCRC = Metastatic colorectal cancer

Mets = Metastasis

Mg = Milligram

mL/min = Milliliters per minute

MRI = Magnetic Resonance Imaging

NCCN = National Comprehensive Cancer Network

NR = Not reached

NSAID = Non‐steroidal anti‐inflammatory drug

NSCLC = Non‐small cell lung cancer

ORR = Objective response rate

PET = Positron emission tomography

PFS = Progression‐free survival

PgP = P‐glycoprotein

PO = By mouth

Q = Every

QID = Four times daily

RAS = Renin angiotensin system gene

RT = Radiation therapy

SUV = Standardized uptake value

TKI = Tyrosine kinase inhibitor

TTF = Time to Treatment Failure

TTF‐1 = Thyroid transcription factor 1

UCC = Urgent care center

ULN = Upper limit of normal

handout bw updated 2.21 bw updated 2.21.17.pdf · cec 2017 2 nsclc: an overview 85% of lung cancer...

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