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
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
Slide credit: clinicaloptions.com
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
Slide credit: clinicaloptions.com
Tumor Immunology: Overview
Dendritic cell
TUMOR
Cytokines
Activated T cell
T-cell clonal
expansion
Resting T cell
LYMPH NODE
Tumor antigen
1
2
3
Slide credit: clinicaloptions.com
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
Slide credit: clinicaloptions.comReck M, et al. N Engl J Med. 2016;375:1823-1833.
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
Slide credit: clinicaloptions.comReck M, et al. N Engl J Med. 2016;375:1823-1833.
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.
Slide credit: clinicaloptions.com
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
Slide credit: clinicaloptions.com
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
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)
Slide credit: clinicaloptions.com
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
– Dosed at 200 mg IV Q3W over 30 min
Atezolizumab: third drug approved; any histology, regardless of PD-L1 expression; improved OS vs second-line docetaxel
– Dosed at 1200 mg IV Q3W over 60 min
Slide credit: clinicaloptions.com
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
Slide credit: clinicaloptions.com
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
Slide credit: clinicaloptions.com
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
Slide credit: clinicaloptions.com
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
Oncology Emergencies in Lung Cancer
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.
Oncology Emergencies in Lung Cancer
Pericardia Effusion/ Pericardial Tamponade
Oncology Emergencies in Lung Cancer
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?