Lung Cancer · 2018-11-13 · • Lung cancer is the leading cause of cancer deaths worldwide in men, and second most common in women. Worldwide, lung cancer occurred in approximately

Lung Cancer

Maria V Garcia Pallas. MDHematology-Medical oncology

Assistant Professor UPR School of Medicine.11-17-18

PRE TEST (T or f)1. Smoking: responsible for approximately 90 % of cases

of LUNG CANCER2. LUNG CA is the most frequent cause of death due to

cancer in PR.3. Most of the patients are diagnosed in STAGE IV 4. Smoking cessation is the most important intervention

to prevent NSCLC.5. Chemoprevention has proved to be highly effective.6. The USPSTF recommends annual screening for lung

cancer with low-dose CT in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years.

EPIDEMIOLOGY

• The majority of data comes from the developed world, where cigarette smoking is the predominant risk factor.

• In the developing world additional risk factors, such as smoke and air pollution, may be particularly important.

• Lung cancer is the leading cause of cancer deaths worldwide in men, and second most common in women. Worldwide, lung cancer occurred in approximately 1.8 million patients in 2012 and caused an estimated 1.6 million deaths.

• In the United States, lung cancer will occur in about 225,000 patients and cause over 160,000 deaths annually.

Smoking Facts

• Tobacco use is the leading cause of lung cancer

• 87% of lung cancers are related to smoking

• Risk related to:– age of smoking onset

– amount smoked

– product smoked

– depth of inhalation

RISK FACTORS of Lung Cancer Second hand smoke - live with smokers have a 24% increase in developing lung

cancer than those who do not.

Occupational exposure – Additional occupational exposures that increase risk include rubber manufacturing, paving, roofing, painting, and chimney sweeping.

-Asbestos - workers who do not smoke have a 5X risk of developing lung cancer than non-smokers, and workers who smoke have a risk 50- 90 X greater than non-smokers

-Nickel/chromate/coal/ mustard gas/ arsenic/ berylium/iron/gold/ haloether and newspaper industry workers (9-15%)

Radon/Radioactive dust

Air Pollution

Genetic susceptibility - plays a contributing role in the development of lung cancer, especially in those who develop the disease at a young age.

Hormonal factors - new findings that hormones effect risks for lung cancer (i.e. estrogen)

Infectious factors -TB or other recurrent infections of the lungs Lung diseases – COPD is associated with 4-6X the risk of nonsmoker

Jemal, CA Cancer J Clin

2008; 58: 71

Cancer Incidence Deaths

Colon 108,070 49,960

Breast 184,450 40,930

Prostate 186,320 28,660

Total 478,840 119,550

NSCLC

Epidemiology

Lung 215,020 161,840

Statistics for 2008

Incidence in Puerto Rico

Chemoprevention of Lung Cancer

• None of the phase 3 trials with the agents β-carotene, retinol, 13-cis-retinoic acid, α-tocopherol, N-acetylcysteine, acetylsalicylic acid, or selenium has demonstrated beneficial and reproducible results.

Lung cancer screening

Lung Cancer Screening Programs

• Screening means testing for a disease when there are no symptoms or history of that disease.

• Doctors recommend a screening test to find a disease early, when treatment may work better.

• The only recommended screening test for lung cancer is low-dose computed tomography (also called a low-dose CT scan, or LDCT).

Risks of Screening

• False-positive result. can lead to follow-up tests and surgeries that are not needed and may have more risks.

• Overdiagnosis. (cases of cancer that may never have caused a problem for the patient) can lead to treatment that is not needed.

• Radiation from repeated LDCT tests can cause cancer in otherwise healthy people.

Who Should Be Screened?

• Have a history of heavy smoking (30 pack years or more), and

• Smoke now or have quit within the past 15 years, and

• Are between 55 and 80 years old.

When Should Screening Stop?

• Turns 81 years old, or

• Has not smoked in 15 years, or

• Develops a health problem that makes him or her unwilling or unable to have surgery if lung cancer is found.

Signs and Symptoms

Trouble breathing

Frequent colds or other respiratory infections

Angina or chest

pain

Bloody sputum

bronchitispneumonia

stridor SOB

wheezing

.Many times there are no symptoms and tumors are found incidentally in pre-op testing for other surgery or emergency situation after an accident. Many times by the time there are symptoms, the disease has become metastatic

NONE

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Diagnostic Tests

• CXR

• PET CT and CT Scans

• MRI

• Sputum cytology

• Fibreoptic bronchoscopy

• Transthoracic fine needle aspiration

Laboratory Tests

Blood Tests

*CBC-to check red/white blood cell & platelets

-to check bone marrow and organ function

*Blood Chemistry Test-to assess how organs

are functioning such as liver and kidney

Biopsy

-to determine if the tumor is cancer or not

-to determine the type of cancer

-to evaluate tumor markers and molecular markers.

Biopsy

Endoscopy

• Bronchoscopy• Mediastinoscopy• VATS (video assisted thoracoscopic surgery)

Bronchoscopy

Mediastinoscopy

VATS (video assisted thoracoscopicsurgery)

Nursing Management for post endoscopic procedures

Bronchoscopy Mediastinoscopy VATS

Monitor V/S; NPO status maintained until return of gag reflex.

Fever up to 101F can be expected afterwards

Monitor VS; potential for bleeding, infection and dyspnea; NPO status until return of gag reflex

Monitor V/S; potential for bleeding, infection and dyspnea; NPO status until return of gag reflex

Post-op complications for those with lung cancer

• Airway obstruction, dyspnea, hypoxemia, respiratory failure

• Anesthesia side effects (N/V)

• Bleeding (hypotension, cardiogenic shock)

• Cardiac dysthymias, CHF, fluid overload

• Fever, sepsis

• Pneumonia

• Pneumothorax

• Pulmonary embolus

• Wound dehiscence

• Prolonged hospitalization

• Death

Nursing pulmonary post-op considerations/interventions

• Positioning in bed, Monitor V/S

• Prevention of respiratory complications– Early ambulation, DB&C, incentive spirometer, managing dyspnea

Prevention of deep vein thrombosis

– Early ambulation

• Pain management

• Infection control

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Two main Types of Lung Cancer:

Small Cell Lung Cancer (20-25% of all lung cancers)

Non Small Cell Lung Cancer (most common ~80%)

Cancer Staging Systems

• The staging system for lung cancer is the TNM System.

• Guides best course of treatment

• Estimates prognosis

• It is also useful when surgery is considered.

TMN Staging system for Lung Cancer

T= Tumors : tumor size, (local invasion)

N= Node : node involvement (size and type)

M= Metastasis : general involvement in organs and tissues

Lung Cancer Staging

• T: Tx, T0, Tis, T1-T4 (T3-tumors greater than 7cm)

• N: N0, N1, N2, N3

• M: M0, M1a, M1b

• Stage 0 - the cancer is in situ• Stage I - the cancer is small and has not spread

to the lymph nodes• Stage II - the cancer has spread to some lymph

nodes near the original tumor• Stage III - the cancer has spread to nearby

tissue or to far away lymph nodes• Stage IV - the cancer has spread to other

organs of the body, such as the other lung, brain, or liver

NSCLC: Stage at Diagnosis

Stage IV 40%

Stage I 10%

Stage II 20%

Stage IIIA 15%Stage IIIB 15%

Ettinger et al. Oncology. 1996;10:81-111.

stage I 60%; stage II 30% to 50%; stage IIIA 10% to 30%; stage IIIB 5%; stage IV 2%.

The 5-year survival

Management

The three main cancer treatments are:

*Surgery (lung resections)

*Radiation therapy

*Systemic therapy : – Chemotherapy

– Targeted therapy

– IO (Check point inhibitors)

Patient Characteristics to Consider in Treatment Decisions

Age

Co-morbidities

PS 0, 1 vs. PS 2

Non-squamous vs. squamous histology

Mutation positive vs. mutation wild type

Non-smoker vs. smoker

Non-Asian vs. Asian

Surgical Candidate Assessment

Size and Tumor location (clinically stage I, II, some IIIa)

Pulmonary function status

Assess Fev1 and DLCO

May need exercise study

May need perfusion scan

Assess cardiac function

Lung resections

• Lobectomy: a single lobe of lung is removed

• Bilobectomy: 2 lobes of the lung are removed (only on R side)

• Sleeve resection: cancerous lobe is removed and segment of the main bronchus is resected

• Pneumonectomy: removal of entire lung

• Segmentectomy: a segment of the lung is removed

• Wedge resection: removal of a small, pie-shaped area of the segment

• Chest wall resection : for cancers that have invaded the chest wall

Radiotherapy in Stage I /II NSCLC

While surgery is the most beneficial therapy radiation alone has been used in patients that can not tolerate surgery.

Smaller tumors have better survival outcomes.

In larger tumors cure is rare but local control may be obtained.

Co-morbidities also influence survival rates

Has been used to preoperatively but with little increase in survival benefit

Cyberknife radiation can be done – must have fiducials placed via bronchoscopy

Radiotherapy in Stage III NSCLC Traditional Dosing 1.8 – 2.0 Gy/ day in 2 dimensions to a total dose of

60 Gy standard of care until late 1990s

Clinical trials have been ongoing looking at dosing up to 90 Gy

Trials have looked at sequential vs concurrent chemo/rads with results showing that concurrent has better outcomes (sequential –happens one after the other. Concurrent – at same time. Can be more toxic)

Trials have also looked at hyperfractionation which also seem to have better outcomes (dose is given twice a day rather than once)

Conformal 3D radiotherapy is considered the new standard of care (tighter fields / less toxicity)

Radiotherapy In Stage IV NSCLC Radiotherapy is used to treat brain metastasis and painful

bone metastasis

Prophylactic with small cell lung cancer – to brain

Stage IV radiotherapy is always palliative

Radiation Patient and Nursing Care

Assess patient and family’s knowledge regarding treatment process

Teach family about treatment plan and appropriate side effects

Assess for skin changes during radiation - be sure patients are aware to monitor skin changes and prevent breakdown

Assess for esophagitis in patients undergoing mediastinal radiotherapy

Assess for pain management

Assess for dietary interventions– be sure patient is able maintain intake of fluids and nutritional intake

Strategies to improve treatment effectiveness

• Better Patient Selection:

– What criteria?

• Better Predictive Markers:

– Which ones?

• Better Treatments:

– Less toxic

– More specific

Histology and Mutations in NSCLC

Targeted therapy for non-small cell lung cancer: current standards and the promise of the futureBryan A. Chan1,2, Brett G.M. Hughes1,2,3

In 1990, there were NO knownMutations.

Changes in the therapeutic landscaping of Lung Cancer.

Non-small Cell Lung Cancer Guideline

Principles of Immunotherapy

Personalized Therapy in Advanced-

Stage NSCLC: Current Therapeutic

Landscape

ChemotherapyCheckpoint Inhibitors†

Targeted TKI Therapy

EGFR

ALK

ROS1

BRAF

V600E

Histologic

subtypeAnti–PD-1

Anti–PD-L1

1970s - today 2000s - today 2015 - today

*± EGFR/VEGF mAbs from 2000s - today.†± PD-1 mAb from May 2017.

Slide credit: clinicaloptions.com

http://www.clinicaloptions.com/

Immune System Function and

Immune Response

Immune surveillance:

Involves both innate and adaptive immune mechanisms

– Tumor-associated antigens can be identified by the immune system and destroyed

Goal of immunotherapy for cancer: to “educate and liberate” underlying anticancer immune responses

Innate Immunity Adaptive Immunity

Identify and destroy foreign or abnormal cells in the body

Nonspecific

First line of defense

WBCs (natural killer cells, neutrophils)

Activation of adaptive response

Specific

Adapts specifically to diverse stimuli

B-cell antibody production

T-cell stimulation

Memory functions


Janeway CA Jr, et al. Immunobiology: the immune system in health and

†

Dendritic cellMast cell

Macrophage

Natural

killer cell

Natural

killer T-cell

B-cell

T-cell

CD4+

T-cellCD8+

T-cell

Antibodie

s

λδ T-cell

Complement

protein

Neutrophil

Eosinophil

Basophil

Granulocytes


T-Cell Response: Accelerate or

Brake?

CD28

OX40

GITR

CD137

CD27

HVEM

CTLA-4

PD-1

TIM-3

BTLA

VISTA

LAG-3

Activating Signals Inhibitory Signals

T-Cell Stimulation T-Cell Inhibition

T cell

Slide credit: clinicaloptions.comMellman I, et al. Nature. 2011;480:480-489.


Immune Checkpoint Pathway

Blockade

Target cell-surface molecules known as immune checkpoint proteins

– Receptor/ligand systems on immune cells

– Modulate the immune response, preventing autoimmunity and minimizing damage to healthy tissue during an immune response

– Interfering with these receptor/ligand systems restores antitumor immunity

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)

Programmed death 1/programmed death ligand 1



Tumor Immunology: Overview

Dendritic cell

TUMOR

Cytokines

Activated T cell

T-cell clonal

expansion

Resting T cell

LYMPH NODE

Tumor antigen

1

2

3



PD-1 as a Target in Cancer Therapy

McDermott DF, Atkins MB. Cancer Med. 2013;2:662-673.

Nivolumab

Pembrolizumab

Pidilizumab

MPDL3280A

MEDI4736

MSB0010718C

PD-L1PD1

Tumor or APC

CD80CD86CD28

Activated T cell

Initial immune response

CytokinesProliferationActivation

Exhausted T cell

Persistent antigen

stimulation

CD80CD86

CD28

Tumor or APC

Communicating With Pts

How do we explain this complicated process to patients and their caregivers?

– Gas and brake pedal analogy

– Pressing the gas pedal = restoring T-cell activity and starting immune response against tumor

– Brake pedal = immune checkpoint

– Lifting the foot off the brake = enabling T cell–mediated immune response to continue

Ledezma B, et al. Cancer Manag Res. 2013;6:5-14. Slide credit: clinicaloptions.com


First-line Immunotherapy

for Advanced Stage NSCLC

Open-label phase III trial

Primary endpoint: PFS (RECIST v1.1, blinded independent central review)

Secondary and exploratory endpoints: ORR, OS, DoR, and safety

Pembrolizumab vs CT as First-line

Therapy for Advanced NSCLC

(KEYNOTE-024)

Pts with stage IV NSCLC

and ECOG PS 0/1, no

previous systemic therapy,

no actionable EGFR/ALK

mutations, no untreated

brain metastases, no

autoimmune disease

requiring therapy, and PD-

L1 TPS ≥ 50% (22C3 assay)

(N = 305)

Pembrolizumab 200 mg IV Q3W

for up to 35 cycles

(n = 154)

Platinum Doublet

Chemotherapy (histology

based) for 4 to 6 cycles

(n = 151)

Stratified by ECOG PS (0 vs 1), histology (squamous vs

nonsquamous), and enrollment region

Until PD (crossover to pembrolizumab

allowed) or unacceptable toxicity

Until PD or unacceptable

toxicity

Slide credit: clinicaloptions.comReck M, et al. N Engl J Med. 2016;375:1823-1833.


KEYNOTE-024: PFS


10

4

8

9

4

4

2

2

315

4

1

15

1

9

9

7

0

1

8

9 1

Pts at Risk,

n 0

10

090

80

70

60

50

40

30

20

10

0

PF

S (

%)

0 3 6 9 12 15 18

62

%

50

%

48

%

15

%

Mos

Pemb

(n =

154)

CT

(n =

151)

Median

PFS, mos

10.3 6.0

HR (95%

CI)

0.50 (0.37-0.68;

P < .001)

Pembrolizumab

Chemotherapy


KEYNOTE-024: OS


13

6

12

1

8

2

3

9

1

1

15

4

0

15

1

12

3

10

6

6

4

3

47

Pts at Risk,

n 0

10

090

80

70

60

50

40

30

20

10

0

OS

(%

)

0 3 6 9 12 15 21

80

%

72

%

70

%

54

%

Mos

Pembro

(n =

154)

CT

(n =

151)

Median

OS, mos

NR NR

HR (95%

CI)

0.60 (0.41-0.89;

P = .005)

Pembrolizumab

Chemotherapy

2

1

18


Randomized phase II cohort G of open-label multicohort trial

Primary endpoint: ORR (RECIST v1.1)

Secondary endpoints: PFS, OS, DoR, activity by PD-L1 TPS, safety

Chemo ± Pembrolizumab as First-line

Therapy for Adv Nonsquamous NSCLC

(KEYNOTE-021)

Pts with stage IIIB/IV

nonsquamous NSCLC

and ECOG PS 0/1, no

previous systemic

therapy, no actionable

EGFR/ALK mutations,

no untreated brain

metastases, no need

for steroids

(N = 123)

Pembrolizumab +

Carboplatin/Pemetrexed Q3W x 4

(n = 60)

Carboplatin/Pemetrexed Q3W x 4*

(n = 63)

Stratified by PD-L1 TPS (< 1% vs

≥ 1%)

*Followed by optional pemetrexed maintenance.

IV dosing: pembrolizumab 200 mg, carboplatin AUC 5 mg/mL/min,

pemetrexed 500 mg/m2.


Langer CJ, et al. Lancet Oncol. 2016;17:1497-1508.

PD Crossover to

pembrolizumab

monotherapy allowed

Pembrolizumab

monotherapy

for up to 2 yrs*


Response

Parameter

Pembro +

CT

Responder

s

(n = 33)

CT Alone

Respond

ers

(n = 18)

Median TTR,

mos1.5 2.7

Median DoR,

mosNR NR

Ongoing

response, %88 78

KEYNOTE-021 Cohort G: ORR by

Independent Central Review

Pembro +

CT

CT

Alone

OR

R, %

(95%

Cl)

10

0

20

30

40

50

60

70

80

90

100

55%

29%

P = .0016

∆26%

Slide credit: clinicaloptions.comLanger CJ, et al. Lancet Oncol. 2016;17:1497-1508.


Summary: First-line Immunotherapy

for NSCLC

Significantly improved median PFS with single-agent pembrolizumab vs chemotherapy for any histology when PD-L1 ≥ 50%

– 10.3 vs 6.0 mos, respectively

No PFS advantage, similar OS for single-agent nivolumab vs chemotherapy

Significantly improved ORR with pembrolizumab + carboplatin/pemetrexed vs chemotherapy in nonsquamous pts (ie, mostly adenocarcinoma)

– 55% vs 29%, respectively

Second-line Immunotherapy

for Advanced Stage NSCLC

Immune Checkpoint Inhibitors in

Pretreated Adv NSCLC: Randomized

Late-Stage Trials


CheckMate 017 CheckMate 057

KEYNOTE-010 OAK

Nonsquamo

us SIIIB/IV

(N = 582)

Nivolumab

Docetaxel

Squamous

SIIIB/IV

(N = 272)

Nivolumab

Docetaxel

Adv NSCLC

with

≥ 1% PD-L1+

tumor cells

(N = 1034)

Pembrolizumab(2 mg/kg)

Docetaxel

Pembrolizumab

(10 mg/kg)

Adv NSCLC

(2L/3L)

(N = 850)

Atezolizumab

Docetaxel

http://www.clinicaloptions.com/oncology

CheckMate-017: Nivolumab vs Docetaxel in Previously Treated Squamous NSCLC

• Open-label, randomized phase III trial

• Primary endpoint: OS

• Secondary endpoint: ORR, PFS, associations with PD-L1 expression, QoL

Stage IIIB/IV

squamous

NSCLC; after

failure of

1 previous

platinum-based tx;

ECOG PS 0-1

(N = 272)

Nivolumab

3 mg/kg IV q2w

(n = 135)

Docetaxel75 mg/m2 IV q3w

(n = 137)

Brahmer J, et al. N Engl J Med. 2015 May 31.]

10

0

80

60

40

20

0

CheckMate-017: Nivolumab vs Docetaxel Efficacy

Brahmer J, et al. N Engl J Med. 2015 May 31. [Epub ahead of print]

0 3 6 9 12 15 18 21 24

Mos

Pro

ba

bil

ity o

f S

urv

iva

l

(% o

f P

ts)

Median

OS,

Mos (95%

CI)

9.2 (7.3-

13.3)

6.0 (5.1-

7.3)

NivolumabDocetaxel

HR: 0.59 (95% CI: 0.44-0.79);

P < .001

1-Yr OS,

Mos (95%

CI)

42 (34-50)

24 (17-31)

Nivolumab vs Docetaxel in Previously

Treated Nonsquamous NSCLC

(CheckMate 057)

Primary endpoint: OS

Secondary endpoints: ORR, PFS, efficacy by PD-L1 expression, safety, QoL

Pretreatment (archival or recent) tumor samples required for measurement of PD-L1 expression by validated, automated IHC assay

Pts with stage IIIB/IV

nonsquamous NSCLC

and ECOG PS 0/1 who

failed

1 prior platinum doublet

chemotherapy ± TKI

therapy

(N = 582)

Nivolumab 3 mg/kg IV Q2W

(n = 292)

Docetaxel 75 mg/m2 IV Q3W

(n = 290)

Until disease progression

or unacceptable

toxicity

Stratified by previous maintenance therapy (yes vs no) and line of therapy (second vs third line)


Borghaei H, et al. N Engl J Med. 2015;373:1627-1639.


Interim Analysis* Extended Follow-up

Nivo (n = 292)

Doc (n = 290)

Nivo (n = 292)

Doc (n = 290)

mOS, mos 12.2 9.4 12.2 9.4

12-mo OS rate, %

51 39 – –

18-mo OS rate, %

– – 39 23

Min follow-up, mos

13.2 17.2

Events/pts, n/N

190/292 223/290 206/292 236/290

HR: 0.73 (96% CI: 0.59-0.89; P =

.002)

HR: 0.72 (95% CI: 0.60-0.88; P <

.001)

CheckMate 057: OS in the ITT

Population

Nivolumab

Docetaxel

100

90

80

70

60

50

40

30

10

0

20

27181596 211230 24 30

Mos

OS

(%

)

Slide credit: clinicaloptions.comBorghaei H, et al. N Engl J Med. 2015;373:1627-1639.

*Formal primary endpoint testing (solid lines in graph).


Atezolizumab vs Docetaxel for Advanced

NSCLC After Platinum Chemotherapy Failure

(OAK)

Primary endpoint: OS in ITT population (first 850 enrolled pts)

Secondary endpoints: PFS, ORR, DoR, safety

Gandara DR, et al. ASCO 2017. Abstract 9001. Rittmeyer A, et al. Lancet. 2017;389:255-265.

Atezolizumab

1200 mg IV Q3W

(n = 425)

Docetaxel

75 mg/m2 IV Q3W

(n = 425)

Metastatic or

locally advanced

NSCLC (2L/3L),

PD on prior

platinum-based

treatment

(N = 850)

Stratified by PD-L1

expression, histology, prior

chemotherapy regimensPD or loss

of clinical

benefit

PD

NPT/Survival

Follow-up*

(n = 332)

NPT/Survival

Follow-up*

(n = 290)

*Pts in atezolizumab arm allowed to continue treatment beyond progression if they were

deriving clinical benefit.

Crossover into the atezolizumab arm not permitted for pts assigned to docetaxel.

Summary: Approved Second-line

Immunotherapy for NSCLC Nivolumab: first drug approved; any histology,

regardless of PD-L1 expression; improved OS vs second-line docetaxel

– Dosed at 240 mg IV Q2W over 60 min

Pembrolizumab: second drug approved; any histology, PD-L1 TPS ≥ 1%; improved OS vs second-line docetaxel


Atezolizumab: third drug approved; any histology, regardless of PD-L1 expression; improved OS vs second-line docetaxel




Immunotherapy

Adverse Event Management

Case Studies

If not vigilant, may result in

more serious immune-

related AEs

Pulmonary

Pneumonitis (< 5%

incidence)

Neurologic

Neuropathy

Guillain-Barre

Myasthenia gravis–like

syndrome

Hepatic

Hepatitis,

autoimmune

Gastrointestinal

Colitis

Endocrine

Hypo- or

hyperthyroidism

Adrenal insufficiency

Hypophysitis

Eye

Uveitis

Iritis

Renal

Nephritis

Skin

Dermatitis

exfoliative

Vitiligo

Alopecia

Immunotherapy Toxicities By

System

Cardiac

Myocarditis



General Guidelines for Management

of Immune-Related AEs Grade 1: asymptomatic to mild

symptoms

– Observation

– Intervention not needed

Grade 2: moderate symptoms

– Local or noninvasive intervention indicated

– Withhold drug, consider re-dose if toxicity resolves to grade ≤ 1

– Low-dose corticosteroids likely needed

– May be able to continue treatment

Grade 3: medically significant but not immediately life-threatening

– Stop immunotherapy immediately

– Hospitalization indicated

– High-dose steroids indicated

– Slow steroid taper over ≥ 1 mo once toxicity resolves to grade ≤ 1

Grade 4: life-threatening consequences

– Urgent intervention

– Permanently discontinue treatment


CTCAE v4.03. June 2010. Atezolizumab adverse reaction management

brochure. Nivolumab adverse reaction management guide.

Pembrolizumab adverse reaction management guide.


Case: Mrs. Smith, revisited

60-yr-old female with history of advanced NSCLC, with adenocarcinoma histology

– ECOG 1

– No EGFR or ALK mutations

– Tumor biopsy positive for PD-L1 (TPS 20%)

PD 6 mos after starting carboplatin/gemcitabine

Started pembrolizumab 15 wks ago

– Well tolerated; no reported side effects

– Radiologic disease stability at 12 wks

Mrs. Smith: Wk 15

Presents with acute onset dyspnea, increased dry cough, no fever or hemoptysis

Examination:

– Moderate work of breathing with some distress

– Diffuse right-sided crackles

– O2 saturation 75% RA sitting, HR 140, BP 85/80

CT of lungs

Mrs. Smith: Discussion

Pt has grade 3/4 pneumonitis

– Life-threatening clinical condition requiring urgent management with high-dose steroids

Admitted to hospital, started on methylprednisolone 60 mg IV BID + O2 support

Symptoms improve, O2 discontinued, discharged home on 6-wk steroid taper

Case 1: Management of Grade 3/4

Pneumonitis

Slide credit: clinicaloptions.comAvailable at: clinicaloptions.com/immuneAETool


Case: Mrs. Jones

76-yr-old woman with metastatic squamous NSCLC, ECOG 1

On anti–PD-1 therapy for 14 wks with partial response

Presents with maculo-papular rash covering all extremities

– Pruritic

Exam is otherwise unnoteworthy

Mrs. Jones: Follow Up

Given topical steroids with worsening of rash after 10 days

Held drug for 4 wks, gave 1 wk of low-dose prednisone with symptom resolution; treatment restarted without issue



Case: Mr. Jackson

69-yr-old male with stage IV NSCLC

Started single-agent pembrolizumab ~10 wks ago

Educated about possible side effects including GI symptoms

Presents to office for sick visit with following report:

– Abdominal cramping, nausea, no emesis

– Anorexia, diarrhea (6-7 episodes/day for 24-36 hrs), weight loss of 5 pounds in past week

– Recent contact with wife who had gastroenteritis

– Afebrile, BP 80/40, HR 150

Mr. Jackson: Management of Grade 3

Colitis

Slide credit: clinicaloptions.comAvailable at: clinicaloptions.com/immuneAETool


Immune-Related Colitis

Focal Active Colitis

Alterations in Crypt Epithelium

Ulceration in Descending Colon

Slide credit: clinicaloptions.comMaker AV, et al. Ann Surg Oncol. 2005;12:1005-1016.


The State of Immunotherapy in Non-

Small-Cell Lung Cancer Immune checkpoint inhibitors are the newest weapon in our

arsenal in the war against lung cancer

– Antibodies against PD-1/PD-L1 and CTLA-4 interfere with immune response modulation, allowing immune system to attack the tumor

3 agents are currently FDA approved to treat NSCLC: nivolumab(PD-1), pembrolizumab (PD-1), and atezolizumab (PD-L1)

– Other agents in late phases of clinical trials with positive randomized phase III data for durvalumab in stage III NSCLC

Careful monitoring for immune-related adverse events with prompt recognition and management critical

– Educate patients about when to report symptoms

Nursing Interventions

• Management of N/V, weakness, fatigue, wt loss, appetite loss, altered taste

• Pain management, education to avoid concern about addiction, pharmacological and non-pharmacological

• Elevate the head of the bed

• Splinting to aid in coughing

• Teach breathing exercises to ↑ diaphragmatic excursion and ↓ work of breathing.

• Provide a vaporizer

• Relaxation techniques to ↓ anxiety r/t SOB

• Encourage energy conservation

• Encourage small amounts of high-calorie and high-protein foods freq.

Nursing Care for Lung Cancer

Patients

To optimize their quality of life, patients need to be aware of ways to control

their symptoms and side effects of their treatments through...

Proper nutrition – Educate patients the need of good diet and adequate hydration. Small frequent meals. High calorie foods to prevent weight loss. Monitor for weight loss and look for early interventions. Educate the patient early in the needs and ways to prevent alterations in taste and weight loss.

Adequate rest – monitor for sleeplessness due to medication interactions, depression, anxiety..etc. When patients come in to clinic, assess sleep patterns. To prevent fatigue, some studies show low impact exercise prevents fatigue. Instruct patients to not take more than 1 nap a day and no more than 30 minutes at a time.

Managing pain and side effects – When starting on pain medications, make sure patients understand side effects and monitor control of pain with medications. Keep pain log to see if changes are needed.

Controlling anemia – monitor labs closely and question patient on visit to see if having signs/symptoms – i.e., Shortness of breath, fatigue, weakness, etc..

Obtaining physical therapy if needed – question patient on visits about his daily activity and any changes in ambulating and transfers, or falls.

Emotional/social support and meeting spiritual needs– monitor for symptoms for depression, family interactions, family attending with patient on visits, offer information on support groups and other community activities with patients of similar needs. Identify depression or depressive symptoms and address as needed.

Educate patients and family about treatment related side effects. Making them aware of the side effects that may occur or ways to prevent/treat them, makes them more accountable for their own health and needs. This can hopefully prevent unnecessary ER visits or hospital admissions.

Nursing Care for Lung Cancer

Patients

SUPERIOR VENA CAVA SYNDROME- SVCS

Oncology Emergencies in Lung Cancer

develops in approximately 3% to 15% of patients with lung cancer.

four times more likely to occur in patients with right- versus left-sided lesions

Presents with: facial edema or erythema, dyspnea, cough, orthopnea, or arm and neck

edema. Also may include hoarseness, dysphagia, headaches, dizziness, syncope,

lethargy, and chest pain.

symptoms may be worsened by positional changes, particularly bending forward,

stooping, or lying down.

Common findings : edema of the face, neck, or arms; dilatation of the veins of the

upper body; and plethora or cyanosis of the face. Periorbital edema may be prominent.

Also may have laryngeal or glossal edema, mental status changes, and pleural

effusion (more commonly on the right side).

Treatment includes: radiotherapy, chemotherapy, thrombolytic therapy and anti-

coagulation, expandable wire stents, balloon angioplasty, and surgical bypass.

Most patients derive relief from obstructive symptoms which may be radiation or

chemotherapy and also when treated with diuretics and steroids


Paraneoplastic Syndrome

Anorexia, weight loss (cachexia): - most common presenting symptoms of ANY cancer. Loss of greater than 10% of

baseline weight. No appetite or desire to eat. (Hormonal supplement, steroids or herbal treatments).

Hormonal

-SIADH (low sodium - nausea, vomiting, headache, weakness, muscle cramping,

decreased appetite, confusion, N/V, diarrhea, decreased output and increase thirst).

Common in small cell lung cancer. Require supplements, fluid restriction,

chemotherapy and other medications (Demeclocycline- tetracycline derivative.)

Hypercalcemia

- high calcium – confusion, abdominal pain, renal stones, bradycardia, anorexia,

N/V, dehydration, pruritus. present in advanced disease with bone mets

- Tx: Hydration, bisphosphonates

Deep venous thrombosis or Pulmonary embolism

Anemia - common in advanced disease or related to treatment.

WBC elevation -can be elevated as a direct response to the cancer (like an

inflammatory response) in some patients. May see the WBC level drop as patient

responds to treatments.

Abnormally large accumulation of fluid within the pericardial sac.

Amounts range from 200 cc – 1800 cc (normal fluid amount is 15-50cc

Can be caused by disease, radiation effects on heart or chemotherapy.

Tamponade results when the heart is compromised from increase amount of fluid and heart can no longer function properly.

Signs/symptoms depend on rate of the accumulation: fatigue, mild dyspnea, orthopnea, and cough. Asymptomatic if accumulates slow, or may decompensate and critically ill if onset is rapid. Vague retrosternal chest pain that may be severe in supine position with palpitations.

More fluid = more pronounced symptoms. May include worsening dyspnea, cough, peripheral edema, and possibly low grade fever.

Severe tamponade =increase in anxiety, restless and confusion.

Treatment –drain the fluid and restore cardiac function; prevention of reaccumulation of fluid; treat the cancer that is the underlying cause. Pericardial catheter may be placed and monitor the re-accumulation of the fluid. Pericardiocentesis may be the definitive treatment. Surgical intervention includes pericardial window or pericardiectomy.


Pericardia Effusion/ Pericardial Tamponade


Pleural Effusion Excess accumulation of pleural fluid within the pleural space and a

common complication of cancer

Malignant pleural effusion is common – fluid may appear to be exudate

Symptoms depend on the amount of fluid present and rate of reaccumulation: shortness of breath, dry cough, pleuritic chest pain, orthopnea, ipsilateral shoulder pain or discomfort

Can become emergent when large amounts of fluid are present and a mediastinal shift may exist that can lead to hemodynamic compromise. If mediastinal shift occurs, trachea may deviate to the opposite side. Decreased, absent breath sounds, or rub may be heard.

Diagnosed with CXR or CT scan

Treatment – thoracentesis to drain off fluid, placement of pleurex catheter, or pleurodesis (sclerosing of the pleura with talc) or pleurectomy

Oncology Emergencies in Lung CancerMalignant Spinal Cord Compression

True neurologic emergency. Without prompt intervention and treatment, may result in paralysis or loss of bowel/bladder control

Symptoms depend on site of met and amount of tumor invasion. Back pain is usually presenting symptom. Pain is localized (at or near site of tumor), or radicular (from irritation of nerve root from compression); shooting pain or burning pain worse with cough or movement. Thoracic vertebrae will cause bilateral pain where cervical or lumbar may be unilateral.

Compression pain is worse with lying flat - arthritic pain is relieved with lying flat.

Palpation of the spine reveal tenderness at the level of tumor involvement.

Diagnosed with plain x-ray of spine, bone scan, CT or MRI (best images are obtained via MRI)

Treatment – Surgery is for lesions with spinal instability, compression from bonefragments and radioresistent areas, or significant pain. Medical management includes – corticosteroids, pain control, radiation therapy and possibly kyphoplasty.

Cancer is so limited...It cannot cripple love.

It cannot shatter hope.It cannot corrode faith.

It cannot eat away peace.It cannot destroy confidence.

It cannot kill friendship.It cannot shut out memories.

It cannot silence courage.It cannot reduce eternal life.

It cannot quench the spirit.

Author unknown

What Cancer Cannot Do

QUESTIONS?

Documents

Lung Cancer · 2018-11-13 · • Lung cancer is the leading cause of cancer deaths worldwide in men, and second most common in women. Worldwide, lung cancer occurred in approximately