Update on the Nursing Management of Cancer Therapy-Related Dermatologic Toxicities

Update on Nursing Management of Cancer Therapy-Related Dermatologic Toxicities

Victoria Sherry, DNP, CRNP, AOCNP®

Oncology Nurse PractitionerAbramson Cancer Center

Hospital of the University of Pennsylvania

Disclosures

Dr. Sherry has no relevant financial relationships to disclose.

Learning Objectives

Distinguish current clinical applications for novel targeted therapies and immunotherapies in cancer

Describe appropriate grading of dermatologic toxicities associated with novel targeted therapies and immunotherapies

Apply evidence-based treatment strategies for dermatologic toxicities associated with novel targeted therapies and immunotherapies

Targeted Therapies and Immunotherapies

Cancer treatment is moving away from traditional chemotherapy

Treatment is increasingly tailored to individual patients Age, performance status, comorbidities Tumor biology and genetics

Patients are now living longer with incurable malignancies

What is targeted therapy?

A drug with a focused mechanism that specifically acts on a well-defined target or biologic pathway, which when inactivated causes regression or destruction of the malignant process

Administered as a single agent or in combination with chemotherapy, radiation, or immunotherapy

Approved for multiple tumor types

How does targeted therapy work?

YY

LigandReceptor

Cell Signaling

Cancer Cell Cancer Cell

Cell SignalingPrevented

Antibody

X

Signal Transduction Molecular Pathways

Maione et al, 2006.

RasRaf1

MEKERK

PI3K

Akt

mTOR

• Cell cycle• CDK and

gene transcription

• Cell Cycle• Cell growth

mRNA translati

on

P

P

P

P

Tyrosine Kinase

Activation

ErbB familyEGFR, HER2/neu

PDGFR, c-KIT

IGFR, cytokines, etc

Phospholipids

Extracellular Signals

Cell Membrane

Intracellular Signals

Turnover/degradation by ubiquitin-proteasome pathway (molecular chaperone: HSP-90)

What is immunotherapy?

The immune system plays a critical role in identifying and destroying cancer cells in the body but has trouble recognizing them due to tumor-induced immune suppression

Tumors use numerous strategies to avoid recognition of the immune system enabling them to grow and spread unrestrained: Conditioning the immune system through induced

immunosuppression Adaptation to immune recognition by altering expression of surface

markers

Swann & Smyth, 2007; Stewart & Smyth, 2011.

What is immunotherapy? (cont.)

Immunotherapy is the clinical application of pharmacological agents that directly induce or substitute for host antitumor immunity

Therapies designed to enhance the immune system identify and destroy tumor cells include: cytokines, monoclonal antibodies, cancer vaccines and coinhibitory receptor blockade (immune checkpoint inhibitors)

Swann & Smyth, 2007; Stewart & Smyth, 2011.

How does the immune system work?

Dunn et al, 2007.

How does immunotherapy work?

TCR = T-cell receptor; MHC = major histocompatibility complex; APC = antigen-presenting cell; Ag = antigen.Pardoll, 2014.

Types of Targeted Therapy

VEGF = vascular endothelial growth factor; BCR-ABL = breakpoint cluster Abelson; HNSCC = head and neck squamous cell carcinoma; HCC = hepatocellular carcinoma; RCC: renal cell carcinoma; GIST = gastrointestinal stromal tumor; CML = chronic myelogenous leukemia; ALL = acute lymphoblastic leukemia; MDS = myelodysplastic syndromes.

Therapy Agent Indication

EGFR inhibitors

Erlotinib GefitinibAfatinibCetuximabLapatinibPanitumumab NecitumumabOsimertinib

Lung, pancreaticLungLungHNSCCBreastColonLungLung

VEGF inhibitors

SorafenibSunitinibVandetinibPazopanibAxitinib

HCC, RCC, thyroidGIST, pancreatic, RCCThyroidRCCRCC

c-MET inhibitors Cabozantinib RCC

Types of Targeted Therapy (cont.)Therapy Agent Indication

BCR-ABL inhibitors

ImatinibDasatinibNilotinib

CML, ALL, MDS, GISTCML, ALLCML

BRAF inhibitors VemurafenibDabrafenib

MelanomaMelanoma

mTOR inhibitorsTemsirolimusEverolimus

RCCBreast, RCC, brain, neuroendocrine, carcinoid

MEK inhibitors TrametinibCobimetinib

MelanomaMelanoma

Types of Immunotherapy

Therapy Agent Indication

PD-1 inhibitorsPembrolizuma

bNivolumab

Melanoma, lung, SCCHN, Merkel cell carcinoma

PD-L1 inhibitors Atezolizumab Melanoma, lung, Hodgkin lymphoma, RCC, SCCHN

CTLA-4 inhibitors Ipilimumab Lung, urothelial cancer,melanoma

Dermatologic Toxicities

Targeted therapies: Approximately 50% to 90% of patients will experience

dermatologic toxicities that affect the skin, hair, and nails Immunotherapies:

CTLA-4 inhibitors: 50% of patients will develop dermatologic toxicity any grade; 2.4% grade 3/4

PD-1 inhibitors: 25.4 % of patients will develop dermatologic toxicity; 40.3% of those who receive an anti-CTLA-4 and anti-PD-L1 combination

Petrou, 2015; Larkin et al, 2015; Minkis et al, 2013; Yervoy® prescribing information, 2015.

How Do Dermatologic Toxicities Affect Patient Outcomes?

Dose reductions Treatment delays

Decreased overall survival Hospitalizations Death

QOL = quality of life; ADL = activities of daily living.Lacouture et al, 2008.

Decreased QOL Impaired ADL and social

functioning

Grading Adverse Events: NCI-CTCAE

Instrumental ADL: preparing meals, shopping for groceries or clothes, using the telephone, managing money

Self-care ADL: bathing, dressing and undressing, feeding, using the toilet, taking medications

NCI, 2010.

Grade 1 Grade 2 Grade 3 Grade 4 Grade 5

Mild ModerateSevere or Medically Significant but not

Immediately Life-Threatening

Life-Threatening

ConsequencesDeath

• Asymptomatic or mild symptoms• Clinical or

diagnostic observations only• Intervention not

indicated

• Minimal, local, or noninvasive intervention indicated

• Limiting age-appropriate instrumental ADL

• Hospitalization or prolongation of hospitalization indicated

• Disabling• Limiting self-care ADL

• Urgent intervention indicated

• Death related to adverse event

NCI-CTCAE Grading Scales for IndividualSkin and Subcutaneous Tissue Disorders

Alopecia Body odor Bullous dermatitis Dry skin Erythema multiforme Fat atrophy Hirsutism Hyperhidrosis Hypertrichosis Hypohidrosis Lipohypertrophy

Nail discoloration Nail loss Nail ridging Pain of skin Palmar-plantar

erythrodysesthesia syndrome Periorbital edema

NCI, 2010.

NCI-CTCAE Grading Scales for IndividualSkin and Subcutaneous Tissue Disorders (cont.)

Photosensitivity Pruritus Purpura Rash acneiform Rash maculopapular Scalp pain Skin atrophy Skin hyperpigmentation Skin hypopigmentation Skin induration Skin ulceration

Stevens-Johnson syndrome Telangiectasia Toxic epidermal necrolysis Urticaria Skin and subcutaneous tissue

disorders - other

NCI, 2010.

Grade 1 Grade 2 Grade 3 Grade 4 Grade 5

Rash acneiformaPapules 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 and are associated with extensive superinfection with IV antibiotics indicated; life-threatening consequences

Death

NCI-CTCAE: Rash

aA disorder characterized by an eruption of papules and pustules, typically appearing on face, scalp, upper chest, and back.BSA = body surface area; IV = intravenous.NCI, 2010.

Dermatologic Toxicities: VEGF Inhibitors

Nexavar® prescribing information, 2013; Sutent® prescribing information, 2015; Votrient® prescribing information, 2015; Inlyta® prescribing information, 2014; Caprelsa® prescribing information, 2016; Schmidinger, 2013; Massey et al, 2015; Balagula & Lacouture, 2011.

Sorafenib Sunitinib Pazopanib Axitinib Vandetanib

Rash 19-40%(Gr 3/4: <1-5%)

14-29%(Gr 3/4: 0-2%)

8-18%(Gr 3/4: <1%)

13% (Gr 3/4: <1%)

53% (Gr 3/4: 5%)

Pruritus 14-20%(Gr 3/4: 0.5-1%)

12%(Gr 3/4: <1%)

7% (Gr 3/4: 0%)

11% (Gr 3/4: 1%)

HFSR 51% (Gr 3/4: 16%)

50% (Gr 3/4: 4-8%)

6-11%(Gr 3/4: 1-2%)

27% (Gr 3/4: 5%)

Xerosis 10-13%(Gr 3/4: 0-0.5%)

15-23%(Gr 3/4: <1%)

10% (Gr 3/4: 0%)

15% (Gr 3/4: 0%)

Hair color changes 20-29%(Gr 3/4: 0-1%)b

38-39%(Gr 3/4: <1%)

Alopecia 14-67% (Gr 3/4: <1%)

8-12%(Gr 3/4: 0%)

4% (Gr 3/4: 0%)

8% (Gr 3/4: 0%)

Skin hypopigmentation

11%(Gr 3/4: 0%)

Dermatologic Toxicities: EGFR Inhibitors

Tafinlar® prescribing information, 2016; Zelboraf® prescribing information, 2016; Larkin et al, 2014; Mekinist® prescribing information, 2015; Balagula et al, 2010; Lynch et al, 2007; Miller et al, 2012.

Gefitinib Erlotinib Cetuximab Panitumumab Lapatinib

Necitumumab (+

Gem/Cisp)Osimertinib Afatinib

Papulopustular rash

47%(Gr 3/4: 2%)

76%(Gr 3/4: 9%)

90%(Gr 3/4: 10%)

57%(Gr 3/4: 7%)

47%(Gr 3/4: 3%)

15%(Gr 3/4: 1%)

41%(Gr 3/4: 0.5%)

78% (Gr 3/4: 14%)

Trichomegaly 11%(Gr 3/4: 6%)

12%(Gr 3/4: 5%)

6%(Gr 3/4: N/A) <1%

Paronychia 10-15% 14%(Gr 3/4: N/A)

14% (Gr 3/4: 0.3%)

25% (Gr 3/4: 2%)

<1%(Gr 3/4: <1%)

7%(Gr 3/4: 0.4%)

25%(Gr 3/4: 0%)

58%(Gr 3/4: 11%)

Mucosal involvement

19%(Gr 3/4: <1%)

11%(Gr 3/4: <1%)

6%(Gr 3/4: <1%)

44%(Gr 3/4: <0%)

11%(Gr 3/4: 1%)

12%(Gr 3/4: 0%)

Pruritus8%(Gr 3/4: <1%)

13%(Gr 3/4: <1%)

11%(Gr 3/4: 1%)

57%(Gr 3/4: 2%)

3%(Gr 3/4: N/A)

7%(Gr 3/4: 0.2%)

41%(Gr 3/4: 0%)

Dermatologic Toxicities: BRAF + MEK Inhibitors

SCC = squamous cell carcinoma.Tafinlar® prescribing information, 2016; Zelboraf® prescribing information, 2016; Larkin et al, 2014; Mekinist® prescribing information, 2015; Peuvrel & Dreno, 2014.

Dabrafenib Vemurafenib Dabrafenib + Trametinib

Vemurafenib + Cobimetinib Trametinib

Rash 27% (Gr 3/4: 1.4%)

37% (Gr 3/4: 8%)

32% (Gr 3/4: 1.1%)

33% (Gr 3/4: 6%)

57%(Gr 3/4: 8%)

Alopecia 45% (Gr 3/4: <1%)

Hyperkeratosis 37% (Gr 3/4: 1%)

24% (Gr 3/4: 1%)

10%(Gr 3/4: 0%)

Pruritus 23% (Gr 3/4: 1%)

10%(Gr 3/4: 2%)

Xerosis 16% (Gr 3/4: 0%)

19% (Gr 3/4: 0%)

10%(Gr 3/4: 0%)

11%(Gr 3/4: 0%)

Photosensitivity

33% (Gr 3/4: 3%)

46% (Gr 3/4: 4%)

Cutaneous SCC 7%(Gr 3/4: 4%)

24% (Gr 3/4: 22%)

6% (Gr 3/4: 6%)

Dermatologic Toxicities: c-MET Inhibitors

Cabometyx® prescribing information, 2016.

Cabozantinib

Palmar-plantar erythrodysesthesia syndrome 42% (Gr 3/4: 8%)

Rash 23% (Gr 3/4: <1%)

Xerosis 11% (Gr 3/4: 0%)

Dermatologic Toxicities: mTOR Inhibitors

Afinitor® prescribing information, 2016; Torisel® prescribing information, 2016; Peuvrel & Dreno, 2014.

Everolimus Temsirolimus

Rash29-59% (Gr 3/4: 0.5-1%)

47% (Gr 3/4: 5%)

Pruritus 13-21% (Gr 3/4: 0-1%)

19% (Gr 3/4: 1%)

Xerosis 13% (Gr 3/4: <1%)

11% (Gr 3/4: 1%)

Nail disorder 14% (Gr 3/4: 0%)

Dermatologic Toxicities: BCR-ABL Inhibitors

Gleevec® prescribing information, 2016. Sprycel® prescribing information, 2016; Pretel-Irazabal et al, 2014; Tasigna® prescribing information, 2016.

Imatinib Dasatinib Nilotinib

Rash 19% (Gr 3/4: 2%)

18% (Gr 3/4: 2%)

38% (Gr 3/4: <1%)

Hypopigmentation 41%

Pruritus 7% (Gr 3/4: 0%)

12% (Gr 3/4: 2%)

21% (Gr 3/4: <1%)

Xerosis 6% (Gr 3/4: 0%)

12% (Gr 3/4: 0%)

Alopecia 7% (Gr 3/4: 0%)

13% (Gr 3/4: 0%)

Dermatologic Toxicities: Immunotherapies

Opdivo® prescribing information, 2016; Keytruda® prescribing information, 2016; Yervoy® prescribing information, 2015; Tecentriq® prescribing information, 2016; Larkin et al, 2015; Bristol Myers-Squibb, 2016.

Nivolumab Pembrolizumab Ipilimumab Atezolizuma

b

Pruritus

23% (Gr 3/4: 0.5%)

28% (Gr 3/4: 0%)

31-45% (Gr 3/4: 0-2.3%)

13% (Gr 3/4: 0.3%)

Rash 28% (Gr 3/4: 1.5%)

24% (Gr 3/4: 0.2%)

29-50% (Gr 3/4: 2%)

13% (Gr 3/4: 0.3%)

Vitiligo 11% (Gr 3/4: 0%)

13% (Gr 3/4: 0%)Combination Therapy Nivolumab + Ipilimumab

Rash 53% (Gr 3/4: 4.8%)

Is there a correlation between dermatologic toxicities and clinical benefit of

targeted therapies and immunotherapies?

Dermatologic Toxicities and Response to Therapy

EGFR: Liu and colleagues (2013) reviewed 33 studies on EGFR TKIs and demonstrated a correlation between rash and clinical benefit Rash was a significant predictor of clinical benefit for NSCLC

patients receiving EGFR inhibitor therapy Rash predicted overall response rate, longer PFS, and longer OS

BRAF: No literature MEK: No literature mTOR: No literature BCR-ABL: No literature

TKIs = tyrosine kinase inhibitors; PFS = progression-free survival; OS = overall survival. Liu et al, 2013; Strumberg et al, 2006; Zheng et al, 2015; Rini et al, 2013; Sanlorenzo et al, 2015.

Dermatologic Toxicities and Response to Therapy (cont.)

VEGF: Patients who experienced skin toxicity while receiving sorafenib

gained significantly more benefit than those without toxicity. Rash and diarrhea are independent protective factors of both PFS and OS

PD-1/CTLA-4: The development of cutaneous adverse events, especially of

vitiligo, in patients affected by melanoma has been shown to be indicative of better treatment response– Skin reactions during pembrolizumab therapy associated with longer PFS– Patients with skin reactions received more treatment cycles

Liu et al, 2013; Strumberg et al, 2006; Zheng et al, 2015; Rini et al, 2013; Hua et al, 2016;Sanlorenzo et al, 2015.

Management of Dermatologic Toxicities

Papulopustular Rash

Photos courtesy of Victoria Sherry, DNP, CRNP, AOCNP®.Lacouture et al, 2011.

Papulopustular Rash Management

National Comprehensive Cancer Network Guidelines Created by task force of experts including oncologists,

dermatologists, an ophthalmologist, and nurse practitioners Few recommendations are evidence-based; most are anecdotal

Multinational Association of Supportive Care in Cancer Guidelines International, interdisciplinary group of experts in dermatology,

medical and supportive oncology, health-related QOL, and pharmacovigilance

Based on nononcology dermatologic trial data as well as oncology trials

Rash: NCCN Recommendations for Prophylactic/Mitigating Treatments

Prophylactic/mitigating treatments (ie, to decrease the severity of rash) Tetracycline antibiotics: minocycline, doxycycline, tetracycline

Not recommended (based on anecdotal or nonrandomized studies) Retinoids: isotretinoin (problem with paronychia), acitretin

Reactive treatment for infection Bacterial culture essential, especially around nose, abscesses, and

pustules on body Antistaphylococcal antibiotics: cephalexin, dicloxacillin Antimethicillin-resistant Staphylococcus aureus antibiotics:

sulfamethoxazole/trimethoprim, linezolid

Burtness et al, 2009.

Rash: MASCC Recommendations for Prevention

Lacouture et al, 2011.

Schedule for Weeks 1–6, 8 of EGFR Inhibitor Initiation

Recommended Not Recommended Comments

TopicalHydrocortisone 1% cream with moisturizer and sunscreen twice daily

Pimecrolimus 1% creamTazarotene 0.05% creamSunscreen as a single agent

38% (Gr 3/4: <1%)

Systemic

Minocycline 100 mg dailyDoxycycline 100 mg twice daily

Tetracycline 500 mg twice daily

Doxycycline is preferred in patients with renal impairment; minocycline is less photosensitizing

Rash: MASCC Recommendations for Treatment



TopicalAlclometasone 0.05% creamFluocinonide 0.05% twice dailyClindamycin 1%

Vitamin K1 cream

Systemic

Doxycycline 100 mg twice dailyMinocycline 100 mg dailyIsotretinoin at low doses 20-30 mg/d

Acitretin Photosensitizing agents

Maculopapular Rash

Photo courtesy of Victoria Sherry, DNP, CRNP, AOCNP®.Lacouture, 2012.

Treatment: Topical corticosteroids Antihistamines

– Grade 1: topical– Grade 2/3: oral

Maculopapular Rash

Photos courtesy of Victoria Sherry, DNP, CRNP, AOCNP®.

Nail Changes Paronychia, slow growth, onycholysis, and fragile

and brittle nails

Photo courtesy of Victoria Sherry, DNP, CRNP, AOCNP®.

Paronychia Management


Treatment Recommended Not

Recommended Comments

Topical

Other

Diluted bleach soaks

Not cutting the nails flushAvoiding skin trauma associated with manual work or wearing tight shoesWearing gloves when handling skin irritants

Recommend final concentration of approximately 0.005% (approximately 1/4-1/8 cup of 6% bleach for 3-5 gal water)

Topical Corticosteroids

Calcineurin inhibitors

Antifungals

Antibiotics

Recommend usage of ultrapotent topical steroids as first-line therapy given cost and availability of these agents

Paronychia Management (cont.)Treatment Recommended Not Recommended Comments

Systemic• Tetracyclines• Antimicrobials:

reserved for culture proven infection

• Biotin for brittle nails

• Empiric antibiotics-employed without culturing lesional skin

• Antifungals

Other

• Silver nitrate chemical cauterization weekly

• Electrodessication• Nail avulsion

Reserved for pyogenic granulomata

Topical • Corticosteroids• Calcineurin inhibitors

• Antifungals• Antibiotics

Recommend usage of ultra potent topical steroids as first-line therapy given cost and availability of these agents


Recommended Not Recommended

Hair loss

Nonscarring:• Minoxidil 2%, 5%

bidScarring:• Class 1 steroid

lotion, shampoo, or foam

• Antibiotic lotionFacial hypertrichosis (hirsutism)

• Eflornithine• Lasers

Waxing, chemical depilatories

Eyelash trichomegaly

• Eyelash trimmings regularly


Management of Hair Changes

Pruritus Management

Lacouture et al, 2011; Santini et al, 2012.


Preventative

Topical Gentle skin care instructions

Systemic • SteroidsTreatment

Topical• Menthol 0.5%• Pramoxine 1%• Doxepin

• Antihistamines• Lidocaine

Nonsedating antihistamine first; some may need adjustment for renal impairment

Systemic• Antihistamines• Gabapentin/pregabalin• Doxepin• Aprepitant

Recommended as second-line treatment only if antihistamines fail

Xerosis Management

No evidence-based guidelines; recommendations from experts

Photo credit: Rash Resource.Lacouture et al, 2011; Bensadoun et al, 2013.

Xerosis Management (cont.)Recommended Not Recommended Comments

Preventive

Topical Bathing techniques using bath oils or mild moisturizing soaps and bathing in tepid water

Regular moisturizing creams

None

Other Avoid extreme temperatures and direct sunlight

TreatmentTopical (mild/moderate)

Emollient creams that are packaged in a jar/tub that lack fragrances or potential irritants

None

Topical (severe)Lacouture et al, 2011.

Xerosis Management (cont.)Treatme

nt Recommended Not Recommended Comments

Topical (mild/moderate)

• Emollient creams that are packaged in a jar/tub that lack fragrances or potential irritants

• Occlusive emollients containing urea, colloidal oatmeal, and petroleum-based creams

• For scaly areas, use exfoliants: ammonium lactate 12% or lactic acid cream 12%

• Urea creams (10-40%)• Salicylic acid 6%• Zinc oxide (13-40%)

• Alcohol-containing lotions

• Retinoids or benzoyl peroxide

More greasy creams for use on the limbs, but caution use of greasy creams on the face and chest

Exfoliants may sting or burn when applied to eroded or erythematous skin—apply only on intact skin

Topical (severe)

Medium-to-high-potency steroid creams (triamcinolone acetonide 0.025%; desonide 0.05%; fluticasone proprionate 0.05%; alclometasone 0.05%)


Hand-Foot Skin Reaction

ESMO, 2014; Weitzman & Cabanillas, 2015.

HFSR Prophylaxis

Pedicure before treatment to remove hyperkeratosis Reduce the exposure of their hands and feet to hot water Emollients (topical exfoliating products: urea-based and

salicylic acid-based) Protection of pressure-sensitive areas (eg, shoes with soft

insoles)

HFSR = hand-foot skin reaction.Lacouture et al, 2008; Schmidinger, 2013.

HFSR Prophylaxis (cont.)

Avoid excessive friction on the skin when applying lotion, during massages, or in the process of everyday tasks, such as typing

Vigorous exercise or activities that place undue stress on the hands and feet should also be avoided, especially during the first month

Thick cotton gloves or socks can be worn to prevent injury and keep palms and soles dry

Lacouture et al, 2008; Schmidinger, 2013.

No HFSR Maintain frequent contact with physician/advanced practice provider to ensure early diagnosis of HFSR

Therapy initiationFull-body skin exam, pedicure, evaluation by orthotist; wear thick cotton gloves and/or socks; avoid hot water,

constrictive footwear, and excessive friction

If symptoms develop at 2-week clinical evaluation or within first month, proceed to next step

HFSR Severity Intervention

MKI = multikinase inhibitor.Lacouture et al, 2008.

Management of MKI-Associated HFSR

Grade 1 Maintain current dose of MKI; monitor for change in severity

• Numbness• Tingling• Dysesthesia• Paresthesia• Painless swelling• Erythema• Discomfort of hand or feet• No interference in ADL

Avoid hot water; use moisturizing creams for relief; wear thick cotton gloves and/or socks; 30%-40% urea

If symptoms worsen after clinical evaluation at 2 weeks, proceed to next step


Management of MKI-Associated HFSR (cont.)


Grade 2 Dose reduction to 50% of dose for 7-28 days

• Painful erythemas• Swelling of hands

and/or feet• Interferes with

patient’s ADL

Treat as with grade 1 toxicity, with the following additions: clobetasol 0.05% ointment, 2% lidocaine, codeine,

pregabalin for pain

If symptoms worsen after clinical evaluation at 2 weeks, proceed to next step




Grade 3 Interrupt treatment for 7 days and until improvement to grade 0-1

• Moist desquamation• Ulceration• Blistering• Severe pain of hands

and/or feet• Patient unable to

perform ADL

Treat as with grades 1 or 2




Photosensitivity Management

No evidence-based guidelines; recommendations from experts

Prophylaxis: Strict photoprotection, including behind windows Clothing and sunscreen with both anti-UVB and UVA filters Sunscreen SPF >30 (UVB) plus 5 (UVA) rating

Treatment: Emollients

Peuvrel & Dreno, 2014; Welsh & Corrie, 2015.

Hyperkeratosis Management

Includes papillomas, cysts, keratoacanthomas (KA), and cutaneous SCC

Treatment: KA and cutaneous SCC should

be removed for histological analysis

When the lesions are too numerous, KA may be destroyed by liquid nitrogen application

Photo credit: Medical Treasure.Peuvrel & Dreno, 2014; Welsh & Corrie, 2015.

Case Study 1: Targeted Therapy

52-year-old Asian man presented with RUQ pain and unexplained weight loss. On physical examination found to be jaundiced

Diagnosed with HCC Deemed inoperable due to extrahepatic disease Treatment plan: sorafenib 400 mg twice daily without

food

RUQ = right upper quadrant.

Case Study 1: Targeted Therapy (cont.)

Prior to beginning therapy, which prophylactic measures would you discuss with this patient? Pedicure before treatment to remove hyperkeratosis Using tepid versus hot water when washing Using emollients Wearing shoes with soft insoles Avoiding excessive friction on the hands and feet Wearing thick cotton gloves or socks to prevent injury and keep

palms and soles dry


Patient begins therapy; when he arrives for his 2-week toxicity evaluation, he presents with grade 2 HFSR


NCI-CTCAE: HFSR

NCI, 2010.

Adverse Event Grade 1 Grade 2 Grade 3 Grade 4

Grade 5

HFSR

Minimal skin changes or dermatitis (eg, erythema, edema, or hyperkeratosis) without pain

Skin changes (eg, peeling, blisters, bleeding, edema, or hyperkeratosis) with pain; limiting instrumental ADL

Severe skin changes (eg, peeling, blisters, bleeding, edema, or hyperkeratosis) with pain; limiting self care ADL

– –

HFSR definition: A disorder characterized by redness, marked discomfort, swelling, and tingling in the palms of the hands or the soles of the feet


Patient is started on clobetasol 0.05% ointment, 2% lidocaine, and pregabalin for pain. Treatment remains at 400 mg twice daily

Patient is re-evaluated in clinic 1 week later and his HFSR is worse (grade 3) despite interventions

Cuesta et al, 2011; Lacouture et al, 2008.


What is the next step? Treatment is held until HFSR resolves to a grade 0/1 2 weeks later, patient is able to restart sorafenib at 400

mg daily. Remains on this dose with a good response for several months with no recurrence of HFSR


Case Study 2: Immunotherapy

68-year-old woman with newly diagnosed metastatic melanoma is started on nivolumab + ipilimumab

No prophylactic treatment is recommended for dermatologic side effects; however, timely recognition is vital for successful management

Case Study 2: Immunotherapy (cont.)

After 6 weeks of therapy, patient calls the clinic with complaints of a pruritic rash

Physical examination reveals a reticular, maculopapular, faintly erythematous rash on the trunk and extremities

NCI-CTCAE: grade 2


Case Study 2: Immunotherapy (cont.)

The patient was prescribed topical corticosteroid cream (betamethasone 0.1% cream) and an oral antipruritic (eg, hydroxyzine, diphenhydramine)

1 week later, there is no improvement. The rash/pruritus now covers 30% of her body and is affecting her ADL (she is unable to sleep at night, embarrassed to go to social events)

Prednisone (0.5-1 mg/kg/day) is added and nivolumab + ipilimumab is held until her symptoms are mild to resolved

Villadolid & Amin, 2015.

Case Study 3: Sequential Targeted Therapy

51-year-old never-smoking woman presents with persistent cough and pain in her lower back

Chest x-ray and computed tomography scan of chest reveal a large right-upper-lobe lung mass with hilar adenopathy

Magnetic resonance imaging scan of the lumbar spine reveals L2–L3 metastases

Biopsy from bronchoscopy reveals adenocarcinoma of the lung, and molecular testing is positive for exon 21 (L858R) EGFR mutation

Case Study 3: Sequential Targeted Therapy (cont.)

Treatment plan is to start her on erlotinib 150 mg/d on an empty stomach

Dermatologic adverse events: 89% any grade rash, 16% grade 3/4 rash

Initiate prophylactic treatment with hydrocortisone 1% cream + moisturizer and sunscreen twice daily

Janjigian et al, 2011.


2 weeks into treatment, patient presents with a grade 3 papulopustular rash on her face, chest, and back

Recommendation is to withhold erlotinib and treat rash with topical clindamycin 1% gel and oral minocycline 100 mg twice daily

Patient education: Avoid hot water; wear sunscreen and protective clothing when in the sun; keep skin moisturized with emollient



4 months into therapy the patient develops hair thinning and trichomegaly

Treatment recommendations: Minoxidil twice daily and

oral biotin 5 mg daily Trim eyelashes carefully!

Photo courtesy of Barbara Burtness, MD.

Future Directions in the Management of Cancer Therapy-Related Dermatologic

Toxicities Conducting well-controlled clinical trials to evaluate agents used to treat dermatological toxicities is essential to create evidence-based guidelines

Establishing whether a rash can improve the efficacy of these agents (ie, BRAF, MEK, mTOR) as this could be a potent tool to ensure that patients have maximum benefit

Taking a multidisciplinary approach when treating dermatologic toxicities by integrating dermatologists into the care of cancer patients

Key Takeaways

Novel targeted therapies and immunotherapies have changed the landscape of cancer treatment; however, they are associated with distinctive dermatologic toxicities that can impair QOL and patient outcomes

Early identification and prompt treatment is essential to maximize benefit and maintain a favorable QOL

Dermatologic toxicity can be a predictor of clinical benefit with some targeted agents and immunotherapies

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Education

Update on the Nursing Management of Cancer Therapy-Related Dermatologic Toxicities