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Melody Mendenhall, RN, MSN, NP-CUCLA Hematology and Oncology

Lung Cancer/Phase I Clinical Trials Team

MANAGEMENT OF LUNG CANCER

OBJECTIVES

Identify the incidence of lung cancer in the US Identify risk factors associated with lung cancer Review Diagnostic Techniques/Staging Distinguish the different histological types of

lung cancer Discuss standard treatment/novel therapy Identify nursing implications in a patient with

lung cancer

ANATOMY OF THE LUNGS

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LYMPH NODES

Lung cancer is the most common cause of cancer death in the US and worldwide

Around 160,000 will die of lung cancer in 2016

1 in 7 smokers will die of lung cancer 1 year survival – <50% overall 5 year survival – 17% overall

BACKGROUND

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RISK FACTORS

• SMOKING• SECOND HAND SMOKE• OCCUPATIONAL EXPOSURE

• ASBESTOS• RADON

• PAST MEDICAL HISTORY• CELL MUTATIONS• CHRONIC LUNG DISEASE

SCREENING

• Based on National Lung Cancer Screening Trial

• 55-74 years old• 30 pack-year smoking

history• Current smoker or quit

within 15 years• Annual low-dose chest

CT scan

CLINICAL PRESENTATION

PRIMARY TUMOR/INTRATHORACIC SPREAD Asymptomatic Cough Shortness of breath Chest DiscomfortHemoptysis Pancoast Tumor/Horner’s Syndrome SVCO/SVCS Laryngeal Nerve Paralysis

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CLINICAL PRESENTATION

EXTRATHORACIC SPREAD Palpable Lymph nodesBone Pain/Fracture Liver Enzyme Abnormalities/Jaundice Focal Neuro deficits/seizures/confusion/headache Spinal Cord Compression**Weight Loss/Fatigue/Fever/Anorexia

ONCOLOGIC EMERGENCY: SVCS

Obstruction of SVC Facial/Neck Swelling,

neck vein distension, *dyspnea, lightheadedness, nausea

CT chest Treatment: Radiation,

chemotherapy, anticoagulation, vascular stent

ONC EMERGENCY: PULMONARY EMBOLISM

Hypercoaguable state in patients with metastatic lung cancer

Presentation: Dyspnea, sudden onset cough, chest pain, tachypnea, tachycardia

CT Angiogram is standard for dx Treatment with thrombolytics (?),

anticoagulation. Anticoagulation for six months.

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ONC EMERGENCY: SPINAL CORD COMPRESSION

Presentation: Back pain, radiating pain, lower extremity weakness, loss of sensation, loss of bowel or bladder control

MRI is standard testing Treat with radiation/surgery

ONCOLOGIC EMERGENCY: HYPERCALCEMIA

Osteolytic metastases, parathyroid hormone related peptide (PTHrP), tumor secretion of 1, 25 dihydroxyvitamin D (lymphomas)

Altered mental status, constipation, abdominal pain, polyuria, polydypsia, fatigue, muscle weakness, nausea, anorexia

Mild: <12mg/dL; Moderate 12-14mg/dL, severe >14mg/dL

Other labs: PTHrP, Ca++, PTH, Vitamin D Treatments: Saline (with or without diuretics),

calcitonin, bisphosphonates, denosumab, dialysis

ONCOLOGIC EMERGENCY: SIADH

ADH increased by tumor production of ADH, pulmonary disease, pain, drugs

Renal tubules more permeable to H20, decreased urine output, increased urine sodium, increased urine osmolality. Results in increased blood volume, dilutional hyponatremia

Confusion, fatigue, lethargy, seizures Treat with fluid restriction, saline, hypertonic

saline, treating underlying condition

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DIAGNOSTICS

CXR, CT Scan, PET/CT Imaging of Brain- MRI Needle Biopsy, Bronchoscopy, Thoracentesis,

VATS, biopsy of metastatic lesion Mediastinoscopy

Lung Cancer Subtypes

Non-Small Cell Lung Cancer

(NSCLC) ~85%

http://www.nci.nih.gov/cancertopics/pdq/treatment/non-small-cell-lung. Accessed 02/05/07.

Small Cell Lung

Cancer(SCLC) ~15%

Large Cell Carcinoma10%-15%

Adenocarcinoma35%-40%

Squamous Cell Carcinoma25%-30%

SMALL CELL LUNG CANCER

One Side of the Lung Ipsilateral Lymph nodes 1/3 Small Cell Cancers Presentation

Cough Shortness of breath Fatigue Weight Loss/Anorexia *SVCS

LIMITED STAGE EXTENSIVE STAGE

Both sides of the lungs Contralateral Lymph nodes Distant Metastasis 2/3 Small Cell Cancers Presentation

Limited stage Symptoms Jaundice Pain *Weight Loss/Anorexia Stridor Pain/Fracture Neurological Symptoms Blood Clot

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SMALL CELL LUNG CANCER TREATMENT

Rare patients are surgical candidates, small tumor size

Cisplatin and Etoposide 2nd line topotecan, irinotecan, nivolumab +/-

ipilumumab (now part of NCCN guidelines) For limited stage disease, combine with

radiation Prophylactic whole brain radiotherapy in limited

stage patients with complete response

NSCLC

Adenocarcinoma 35-40% Driving mutations are most commonly found in

adenocarcinomas Squamous Cell Carcinoma

25-30% Large Cell Carcinoma/NSCL NOS

10-15 Treatments vary widely depending on

staging/histology/molecular testing- constantly evolving

TNM STAGING

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TNM STAGING

TNM STAGING

STAGE I-II NSCLC

Surgery Radiation is an option, for patients who are not

surgical candidates Adjuvant therapy, chemotherapy for stage II and

high-risk IB (large tumor size, vascular invasion, unknown lymph node status)

Radiation for patients with positive surgical margins

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ADJUVANT THERAPY

ADVANCED NSCLC. STAGE III

Mediastinal LN involvement

Supraclavicularor scalene LN

Primary tumor invades local structures (heart, spine,greatvessels, etc)

STAGE III TREATMENT OPTIONS

Surgery if possible, sometimes neo-adjuvant chemotherapy is an option

Chemo/Radiation vs sequential chemotherapy and radiation

Drugs typically given with concurrent radiation are Taxol/Carboplatin (weekly) or Carboplatin/Etoposide.

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ADVANCED NSCLC. STAGE IV

M1a Pleural or pericardial effusion Tumor with pleural nodulesNodule in the contralateral lung

M1b Cancer spread outside of the chest

Chemotherapy vs. Supportive Care

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TREATMENT PARADIGMS AFTER 2004 Determination of histology at diagnosis is mandatory.

There are differences in survival between platinum based doublets.

Three drugs may be better than two, in specific populations.

Maintenance therapy is a novel strategy and an option.

Targeted therapies have become the first line standard of care for driving mutations

Immunotherapy has become a very important treatment option

P=0.03 P=0.05

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Targeted Agents

TARGETED THERAPIES

Targeting Vascular Endothelial Growth Factor(VEGF)Bevacizumab- first line (non-squamous only), Carbo/TaxolRamicirumab- second line (all histologies), docetaxel

Targeting Epidermal Growth Factor Receptor (EGFR) Monoclonal antibody against EGFR Tyrosine kinase inhibitors (erlotinib, afatinib),

osirmertinib for 2nd line (T790m mutation)

Targeting Anaplastic Lymphoma Kinase (ALK) crizotinib

ANGIOGENESIS

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PHASE III TRIAL IN NON-SQUAMOUSNSCLC: ECOG 4599 (N=855)

EligibilityNo previous chemotherapy

Non-squamous cellNo hx of hemoptysisNo CNS metastases

CPPaclitaxel 200 mg/m2

Carboplatin AUC 6(Q3 weeks) x 6 cycles

CPBCP x 6 cycles

+Bevacizumab (15 mg/kg)

Q3 weeks to DP

No crossover tobevacizumab

Stratification Variables:RT vs. no RTStage IIIB or IV vs. recurrentWt loss <5 % vs. > 5%Measurable vs. non-measurable

Sandler, et al. NEJM 355:2542-2550, 2006

Sandler, et al. NEJM 355:2542-2550, 2006

2-year survival 23 vs. 15%

HR=0.80

BEVACIZUMAB

RAMICIRUMAB

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ONCOGENE ADDICTION

Some cancers may be driven by a single mutation, without which the cancer cells dies.

Lung Cancer Mutation Consortium

INCIDENCE OF SINGLE DRIVER MUTATIONS

Chemotherapy

vs. 

Targeted Agent

For 1st Line Therapy 

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IPASS STUDYGefitinib vs. Carbo/Taxol in First Line Therapy in Asian Patients

Mok, ESMO 2008

Advanced NSCLCNo prior therapy

Never or light ex-smokersN+ 1217

Carbo-Taxol IVEvery 3 weeks

Iressa 250 mg/day

RANDOMI

ZATI

ON

Primary EndpointPFS

Secondary:ORROSQOLSafetyDisease-related symptoms

TYROSINE KINASES AND TKI’S

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CLINICAL RESPONSESAND RESISTANCE

ALK INHIBITOR: CRIZOTINIB

~250 kb ~300 kb

t(2;5) ALK genebreakpoint region

2p23 regionTelomere Centromere

3’ 5’

FISH ASSAY FORALK REARRANGEMENT*

Break-apart FISH assay for ALK-fusion genes1

ALK 29.3

EML4 42.3

ALK break-apart FISH assay[Courtesy John Iafrate, Massachusetts General Hospital]

1Shaw AT et al. J Clin Oncol 2009;27:4247–4253

1Shaw AT et al. J Clin Oncol 2009;27:4247–4253

q36.1

q36.3q37.2

q34

q32.1

q32.3

q33.2

q31.3

q24.3

q24.1

q23.2q22.2q22.1

q21.2q14.3

q14.1

q12.3q12.1

p12

p13.2p14

p16.1

p16.3

p22.1

p23.2

p22.3

p24.1

p24.3

p25.2

q36.1

q36.3q37.2

q34

q32.1

q32.3

q33.2

q31.3

q24.3

q24.1

q23.2q22.2q22.1

q21.2q14.3

q14.1

q12.3q12.1

p12

p13.2p14

p16.1

p16.3

p22.1

p23.2

p22.3

p24.1

p24.3

p25.2

Split signalNon-split signal

*Assay is positive if rearrangements can be detected in ≥15% of cellsFISH = fluorescence in situ hybridization

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TARGETS UNDER DEVELOPMENT

KRAS mutation ROS1 fusion: sensitive to crizotinib RET fusion PI3K/mTOR pathway MET: overexpression vs mutation:

Crizotinib, met antibodies

IMMUNOTHERAPY/CHECKPOINT INHIBITORS

IMMUNE CHECKPOINT INHIBITION

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PDL1 STAINING

IMMUNOTHERAPIES IN NSCLC

Opdivo (nivolumab) approved for 2nd line treatment in squamous cell NSCLC March 2015

Keytruda (pembrolizumab) approved for 2nd line treatment in PDL1 positive (any histology) patients Oct 2, 2015

Opdivo (nivolumab) expanded for use in any histology NSCLC Oct 9, 2015

Tencentriq (atezolizumab) PDL1 inhibitor approved for 2nd

line NSCLC in October 2016 Ketyruda (pembrolizumab) approved for 1st line NSCLC in

patients who are PDL1 high (>50%) in October 2016 Many immunotherapy combinations are currently being

studied.

CHECKPOINT INHIBITOR SIDE EFFECTS

Immune-related side effects, very different than chemotherapy

Most common side effects are fatigue, thyroid dysfunction, and rash.

Other side effects include pneumonitis, colitis, pancreatitis, hepatitis, adrenalitis, hypophysitis, type 1 diabetes

Treatment may include withholding treatment and administration of steroids

Side effects can quickly become life threatening

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PNEUMONITIS

STAGE IV TREATMENT SUMMARY: 1ST LINE

- Targeted therapy if applicable (EGFR, ALK, ROS1) Examples: erlotinib, afatinib, crizotinib

- -Chemotherapy - Pembrolizumab for PDL1-high patients

STAGE IV SUMMARY- SECOND LINE AND BEYOND

-Newer generation targeted therapies osimertinib, alectinib

PD1 inhibitors Second-line chemotherapy Clinical trials Targeted therapies (including clinical trials) can

be guided by genomic testing of either tumor specimen or circulating tumor cells

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CHEMOTHERAPY REGIMENS

Alimta (pemetrexed) + Carboplatin or Cistplatin Non-squamous histology

Gemzar (gemcitabine) + platinum Taxotere (docetaxel) + platinum +/-ramicirumab Taxol (paclitaxel) + platinum +/- bevacizumab

(adenocarcinoma only) Etoposide + platinum Gemcitabine + vinorelbine

NURSING IMPLICATIONS

Diagnosis (supportive care, emotional support) Treatment decision making (education) Surgery Radiation Chemotherapy Follow-up

CASE STUDY

64 year-old female, who has never smoked presents to her dermatologist for an enlarging skin nodule on her scalp. A biopsy is taken and consistent with adenocarcinoma- lung primary.

Further imaging shows multiple right lung nodules, enlarged right paratracheal and subcarinal lymph nodes

MRI of the brain is negative Molecular studies: EGFR, ALK, KRAS negative PDL1 testing = 80%

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QUESTIONS

What is her Stage? What is first line therapy for her? What are some nursing considerations for a

patient like this What is an appropriate second line therapy

CASE STUDY

75 year-old male with metastatic squamouscell carcinoma who has been on pembrolizumab for 4 months, with a good response to treatment. His labowork has been normal.

He comes to clinic for treatment and his LFTsare mildly elevated- AST 80, ALT 104, Alk Phos180, normal bilirubin

QUESTIONS

Is this cause for concern? Why or why not? What, if any, actions need to be taken? Should treatment be withheld?

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THANK YOU FOR YOUR ATTENTION!