3.3 Lung Cancer - Comeau

what causes 90% of all lung cancer cases?

cigs

what are some environmental exposures that can cause lung cancer?

asbestos

2nd hand smoke

what is the number 1 method to prevent lung cancer?

DONT SMOKE

most common stage of lung cancer at diagnosis

IV distant/ metastatic

overall survival of stage IV (distant/ metastatic lung cancer)

9.7% of ppl

what is the gold standard screening procedure for lung cancer?

low dose helical CT

what are the requirements to be screened for LC?

must be 50-80 yrs old

must have >/= 20 pack year

must have smoked or is currently smoking

(MUST HAVE ALL)

if a pt meets all requirements for LC screening, how often should they be screened?

every year big dog

how to determine pack year?

number of packs a day x number of years smoked

what are the two types of LC?

small cell

non-small cell

what are the types NSCLC?

adenocarcinoma

squamous cell carcinoma

large cell carcinoma

describe the metastasis pathway for LC

lungs —> lymph nodes —> brain —> bone —> liver —> adrenal glands

non metastatic LC can be treated with…

local methods (radiation and surgery)

metastatic LC can be treated with…

systemic tx (can add local methods too)

60-70% of all LC’s are extensive small cell LC,

1. what is the cure rate

2. what is the median survival after diagnosis

3. what percent of pts make it to 5 years post diagnosis?

1. 0%

2. 8-13 months

3. 1-2%

limited small cell LC treatment goal

cure

extensive SCLC treatment goal

palliative

limited stage small cell LC:

what is the treatment sequence?

concurrent chemoradiation then immunotherapy if stable or better

What is the purpose of adding chemotherapy to radiation in limited-stage disease LC?

increases survival odds

small cell LC:

What is the preferred chemotherapy regimen with CRT?

cisplatin + etoposide

what does platinum doublet mean??

platinum + other drug

SCLC:

if cisplatin is CI or not tolerated, what can we give instead?

carboplatin

What supportive care is important with platinum therapy?

fluids

small cell LC:

what class of immunotherapy agents are used?

immune checkpoint inhibitors

what are the two classes of immune checkpoint inhibitors

PDL1 and PD1 inhibitors

Cisplatin and Carboplatin ADE/Tox

CINV

renal and electrolyte abnormalities

ototoxicity

which platinum causes more myelosuppression?

carboplatin

What is the risk of giving G-CSF with concurrent chemoradiation (CRT)?

increased risk of death (yikes)

how do immunotherapy agents work for LC?

they inhibit T cell deactivation and increase T cell activation so the T cells can attack the cancer cells

similarities between the immunotherapy options for LC

same ADEs

same MOA

all given IV

what are the PD1 inhibitors?

Nivolumab

Pembrolizumab

Cemiplimab

what are the PDL1 inhibitors?

Atezolizumab

Durvalumab

Why must patients be evaluated for autoimmune disease before immunotherapy?

Immunotherapy can worsen autoimmune diseases

what is the drug and dose to treat moderate to severe immunotherapy ADE?

prednisone 1 mg /kg / day

What may need to happen to PD-1/PD-L1 therapy in moderate–severe irAEs?

Hold or discontinue therapy

How long should steroids be tapered in severe irAEs?

long taper

When should PJP/pneumonia prophylaxis be started in irAE treatment?

if pt is on steroid (prednisone) for 4 weeks or more

pts with severe IRAE on steroids for 4 weeks or more should be started on ______ for PJP prophylaxis

bactrim

What is the most common endocrine irAE?

hypothyroidism

How often should TSH and fT4 be monitored during immunotherapy?

every 4-6 weeks

What defines overt hypothyroidism?

High TSH + low fT4

if a pt has overt hypothyroidism (High TSH + low fT4) they should be treated with…

levothyroxine

How is irAE dermatitis managed?

topical agents

if itchy give po antihistamine (diphenhydramine)

What non-pharma care is used for irAE colitis?

BRAT diet and hydration

What medication can be used for short-term symptom control in colitis?

loperamide

What is the most common cause of death from irAEs?

Pneumonitis

What must be ruled out in suspected pneumonitis from immunotherapy?

infections (CAP)

What antibiotics cover atypicals in pneumonitis?

Levofloxacin, azithromycin, doxycycline

What is the first-line treatment for extensive-stage small cell LC?

platinum + etoposide + immunotherapy then do immunotherapy till progression

which immunotherapy medications are used for extensive small cell LC?

atezolizumab or durvalumab

brain radiation is obviously toxic af, what drug should be added to help prevent neurocognitive impairment?

memantine

non-small cell LC treatment goals:

1. respectable /local

2. inoperable

3. metastatic

1. cure

2. control dx

3. palliative

what is the driver mutation for non small cell LC?

EGFR sensitizing

what is the most common driver mutation target in non small cell LC?

EGFR

pts with a ____ % of tumor cells with PDL1 respond better to immunotherapy

a. lower

b. higher

b

non small cell LC:

treatment for nonresectable, locally advanced stage IIIB-C

platinum doublet with concurrent radiation

Why is chemotherapy added to radiation for non small cell LC?

increases efficacy of radiation therapy

adenocarcinoma treatment options

platinum with either pemetrexed, etoposide, OR paclitaxel

What regimens are used for adenocarcinoma (only)?

platinum + pemetrexed

squamous non small cell LC treatment option

platinum with either etoposide or paclitaxel

which chemo agent is CI in squamous non small cell LC?

pemetrexed

What is the initial treatment for unresectable Stage IIIB–C NSCLC?

Concurrent chemoradiation (CRT)

What is given after CRT if disease is stable or improved?

immunotherapy (durvalumab)

What is used after CRT in patients with EGFR-mutated NSCLC?

Osimertinib

What is the first step in treating Stage IV metastatic NSCLC?

check for targetable mutations

Patient has adenocarcinoma with a targetable mutation—what is first-line treatment?

targeted therapy for that mutation

if a pt has stage IV metastatic NSCLC (adenocarcinoma or squamous cell carcinoma, WITH NO mutations, what determines treatment?

PDL1 expression

How is Stage IV NSCLC treated if PD-L1 ≥ 50%?

single agent immunotherapy (pembrolizumab) or pembrolizumab + platinum doublet

How is Stage IV NSCLC treated if PD-L1 < 50%?

pembrolizumab + platinum doublet

What are the two most common EGFR mutations in NSCLC?

• Exon 19 deletion

• L858R exon 21 mutation

What is the preferred first-line treatment for EGFR-mutated NSCLC?

Osimertinib

What combination can be used with osimertinib in EGFR-mutated NSCLC?

Osimertinib + platinum + pemetrexed

What is another targeted combination for EGFR-mutated NSCLC?

Lazertinib + amivantamab

What is the are the common adverse effect of osimertinib?

rash and diarrhea

describe the rash that osimertinib causes in over half of the pts on it

dry skin with acne like rash

non pharmacological measures to treat osimertinib induced rash

avoid sun, use sunscreen, and moisturize

how is a mild EGFR inhibitor (osimertinib) rash managed?

topical agents (hydrocortisone and clindamycin)

how is moderate EGFR inhibitor (osimertinib) induced rash treated?

try different topical steroids AND doxycycline or minocycline

how to treat osimertinib induced diarrhea?

give loperamide

what is a common ADE seen with EGFR-targeted therapies (lazertinib + amivantamab)?

Rash/skin toxicities (~40%)

How are EGFR-related skin toxicities managed prophylactically?

doxycycline or minocycline

clindamycin topical

moisturizer

What receptors does amivantamab target?

EGFR

MET

What are common ADE of amivantamab?

Peripheral edema

Infusion-related reactions

What is a major systemic risk with the lazertinib + amivantamab regimen?

VTE

how to prevent VTE due to lazertinib + amivantamab?

prophylactic anticoagulation

When is single-agent immunotherapy indicated up-front in Stage IV NSCLC?

PD-L1 ≥ 50% on tumor cells

What medication is most used for single-agent immunotherapy for nsclc?

pembrolizumab

Can chemotherapy + immunotherapy be used regardless of PD-L1 expression?

yes (any pt)

When is chemo + immunotherapy strongly recommended based on PD-L1?

PDL1 < 50%

What is the chemo + immunotherapy regimen for adenocarcinoma?

carboplatin + pemetrexed + pembrolizumab

What is the chemo + immunotherapy regimen for squamous cell carcinoma?

carboplatin + paclitaxel or nab-paclitaxel + pembrolizumab

What supportive care is used to prevent myelosuppression and mucositis due to pemetrexed ( in a pt with non-squamous adenocarcinoma)?

folic acid and vitamin B12

What is used to prevent dermatologic toxicities with pemetrexed? (in a pt with non-squamous adenocarcinoma)

dexamethasone

Which irAE is more common with platinum/pemetrexed/pembrolizumab regimens?

Nephritis

most common ADE of pembrolizumab

AKI (nephritis)

What is a key adverse effect of paclitaxel?

Infusion-related reactions (due to inactive ingredient)

What premedications are required for paclitaxel to prevent infusion reactions?

H1 inhibitor + H2 inhibitor + dexamethasone

Are premedications required for nab-paclitaxel to prevent infusion related reactions?

nah fam

What causes SVC syndrome?

Compression of the superior vena cava → obstruction of blood flow

How is SVC syndrome treated in small cell lung cancer (SCLC)?

Chemotherapy ± radiation