Heme/Onc exam 3

what is the leading cause of lung cancer

cigarette smoking

lung cancer risk factors

-cigarette smoking

-radon gas

-asbestos

-chemicals

-first degree relatives with lung cancer

lung cancer prevention

-avoid tobacco

-maintain a healthy diet

-offer screening to high risk individuals

lung cancer screenings

low dose CT scan annually for high risk individuals

definition of high risk for lung cancer

-individuals 50 to 80 years of age

-minimum of 20 pack year smoking history

-still smoking or have quit for less than 15 years

risks of lung cancer screening

-false positives

-risk of radiation exposure from screening

local clinical presentation of lung cancer

-cough, dyspnea

-chest pain or discomfort

-hemotysis

systemic clinical presentation of lung cancer

-anorexia

-weight loss

-fatigue

extra-pulmonary (site of metastases) clinical presentation of lung cancer

-neurologic deficits

-bone pain or fractures

-liver dysfunction

paraneoplastic syndrome (SCLC) clinical presentation

-hypercalcemia

-syndrome of inappropriate secretion of ADH

-hypercoaguable state

lung cancer diagnosis

-patient history and physical exam

-performance status

-visualization of the tumor (CT/ PET scan)

-tissue sampling for pathologic assessment

what are the two types of lung cancer

Small cell and non-small cell

what is the most common type of lung cancer

non-small cell lung cancer

what lung cancer type is more aggressive and rapidly growing

small cell lung cancer

what lung cancer has the liver, bone, adrenal glands, kidneys, and CNS as sites of metastases

non-small cell lung cancer

what lung cancer has the bone and CNS as sites of metastases

small cell lung cancer

what lung cancer is subdivided into squamous and nonsquamous histologies and treatment is guided by stage, histology, and presence of biomarkers and/or targeted mutations

non-small cell lung cancer

what lung cancer has paraneoplastic syndromes, treatment guided by stage, and no current role for evaluation of biomarkers and/or targeted mutations

small cell lung cancer

what lung cancers are non-squamous

adenocarcinoma and large cell

what type of lung cancer has a strong correlation with smoking, molecular targets very rare, and arises from squamous cells that line the inside of the airways

squamous

what type of lung cancer is more common in nonsmokers and women, associated with molecular targets, and arises from bronchial epithelium

adenocarcinoma

what type of lung cancer has large, bulky tumors and tends to grow and spread quickly

large cell

what stage is nodal involvement first seen in non-small lung cancer

IIA

what stage is metastases first seen in non-small lung cancer

IVA

stage I NSCLC

-tumor is

-minimally invasive

-no nodal involvement

Stage II NSCLC

-large tumor

-may have more than one nodule in same lobe

-may involve nearby lymph nodes

stage III NSCLC

-may have tumor in more than one lung lobe on same side, tumor may invade nearby structures

-extensive lymph node involvement in mediastinum or other side of body

Stage IV NSCLC

may have separate tumor in opposite lung or spread of cancer to structures outside the thoracic space

treatment modalities of NSCLC

-surgery

-radiation

-chemo, immunotherapy, targeted therapy

treatment overview of local disease stages I-II NSCLC

-cure

-surgery

-radiation

-systemic treatments

treatment overview of locally advanced disease stage III NSCLC

-prolong survival

-surgery

-radiation

-systemic treatments

treatment overview of metastatic stage IV NSCLC

-prolong survival

-systemic treatments

treatment of non-squamous metastatic NSCLC

-cisplatin + pemetrexed

-carboplatin + pemetrexed

treatment of squamous metastatic NSCLC

-cisplatin + paclitaxel

-carboplatin + paclitaxel

-carboplatin + albumin-bound paclitaxel

drug class of cisplatin and carboplatin

platinum coordination complex

MOA of cisplatin and carboplatin

-platinum binds to nucleophilic sites on DNA and the drug behaves like an alkylating agent

-cross links DNA strands together by forming platinum crosslinks

-DNA replication and transcription halted

-cell apoptosis

how are cisplatin and carboplatin eliminated

renal

dose limiting toxicities of cisplatin

-AKI

-N/V

-myelosuppression

-ototoxicity

-neuropathy

carboplatin dosing equaiton

(CrCl +25) x AUC

dose limiting toxicities of carboplatin

-myelosuppression

-N/V

drug class of pemetrexed

anti-metabolite

MOA of pemetrexed

inhibits dihydrofolate reductase (DHFR) and thymidylate synthase interrupting purine and pyrimidine synthesis

what CrCl is contraindicated for pemetrexed

45

dose limiting toxicities of pemetrexed

-myelosuppression

-mucositis

-skin rash

supportive care of pemetrexed

-folic acid starting 1 week prior to pemetrexed

-vitamin IM every 9 weeks

-dexamethasone BID x 3 days, starting the day before treatment

biomarkers of NSCLC

-EGFR

-ALK

-KRAS

-ROS1

-BRAF

-MET

-RET

-NTRK

-HER2

-PD-L2

treatment of metastatic NSCLC with a targeted genetic mutation

kinase inhibitor targeted to mutation

treatment of metastatic NSCLC with no mutation and PD-L1 positive >50%

-immunotherapy alone

-immunotherapy + chemo

treatment of metastatic NSCLC with no mutation and PD-L1 positive 1-49%

immunotherapy + chemo

treatment of metastatic NSCLC with no mutation and PD-L1 negative

immunotherapy + chemo

what is the most common genomic alteration in NSCLC

EGFR mutations

EGFR mutation types in NSCLC

-EGFR exon 19 deletion

-EGFR exon 21 (L858R) point mutation

first line treatment for metastatic EGFR exon 19 deletion or exon 21 (L858R) point mutation NSCLC

-osimertinib

-osimertinib + (carboplatin or cisplatin) / pemetrexed (nonsquamous)

-lazertinib + amivantamab

first line treatment for metastatic EGFR S768I, L861Q, or G719X NSCLC

afatinib or osimertinib

first line treatment for metastatic EGFR exon 20 (T790M) insertion mutation NSCLC

amivantamab + carboplatin / pemetrexed (nonsquamous)

subsequent treatment after progression for metastatic NSCLC

-retest for additional targetable mutations

-amivantamab or osimertinib, if not used

-chemo with or without immunotherapy

drug class of osimertinib

receptor tyrosine kinase inhibitor, EGFR

MOA of osimertinib

irreversible EGFR TKI, selective for T790M resistance mutation

adverse effects of osimertinib

-nail changes

-skin rash

-elevated LFTs

-QTc prolongation

-interstitial lung disease

-reduced ejection fraction

-severe skin rash syndromes

what cell surface receptor limits T cell activity early in the immune response

CTLA-4

what cell surface receptor reduces T cell activity later in the immune response

PD-L1/PD-1

CTLA-4 inhibitors

Ipilimumab

Tremelimumab

PD-1 inhibitors

Pembrolizumab

Nivolumab

Cemiplimab-RWLC

PD-L1 inhibitors

Atezolizumab

Durvalumab

immune checkpoint inhibitors used for metastatic NSCLC PD-L1 >/=50%

-monotherapy

-atezolizumab

-cemiplimab

-pembrolizumab

treatment of metastatic nonsquamous NSCLC regardless of PD-L1 expression

-pembrolizomab + pemetrexed + cisplatin/carboplatin --> pembrolizumab + pemetrexed

-cemiplimab + pemetrexed + cisplatin/carboplatin --> cemiplimab +/- pemetrexed

treatment of metastatic squamous NSCLC regardless of PD-L1 expression

-pembrolizumab + carboplatin + paclitaxel / albumin-bound paclitaxel --> pembrolizumab

-cemiplimab + cisplatin/carboplatin + paclitaxel --> cemiplimab

other strategies for metastatic NSCLC regardless of PD-L1 expression

-bevacizumab + atezolizumab + chemo

-ICI + ICI

-ICI + ICI + chemo

how long is treatment for metastatic NSCLC limited to

2 years

subsequent treatment after first line targeted therapy of metastatic NSCLC

-retest for additional targetable mutations

-alternative targeted therapy not previously used

-chemo with or without immunotherapy

subsequent treatment after first line immunotherapy of metastatic NSCLC

-retest for additional targetable mutations

-alternative chemo

treatment of stage III resectable NSCLC

treat like stage II

treatment of stage III unresectable NSCLC and a candidate for radiation

-radiation + chemo

-consolidation therapy

treatment of stage III unresectable NSCLC and a not candidate for radiation

treat like stage IV

treatment of stage III NSCLC

-chemo + radiation

THEN

-assess response

THEN

-EGFR - osimertinib until progression

OR

-immunotherapy - durvalumab for 1 year

regimen for non-squamous stage III NSCLC

-cisplatin + pemetrexed

-carboplatin + pemetrexed

regimen options for stage III NSCLC

-carboplatin + paclitaxel

-cisplatin + etoposide

first line treatment of stage II NSCLC

surgery

treatment of stage II NSCLC with negative margins

adjuvant systemic treatment

treatment of stage II NSCLC with positive margins

-rerescetion or radiation

+

-adjuvant systemic treatment

adjuvant systemic treatment with stage II NSCLC with a targetable mutation

-osimertinib (EGFR) +/- chemo

-alectinib (ALK)

-selepercatinib (RET)

true or false: immunotherapy should be administered in the setting of a targetable genetic mutation

false

adjuvant systemic treatment with stage II NSCLC with no mutation

-chemo + immunotherapy

-platinum doublet

-atezolizumab for 1 year

-pembrolizumab for 1 year

chemo options for stage II non-squamous NSCLC

-cisplatin + pemetrexed

-carboplatin + pemetrexed

chemo options for stage II squamous NSCLC

-cisplatin + gemcitabine

-cisplatin + docetaxel

-carboplatin + gemcitabine

first line treatment of stage I NSCLC

surgery

treatment of stage I NSCLC with negative margins

observe

treatment of stage I NSCLC with positive margins

reresection or radiation

what are the two stages of SCLC

limited and extensive

limited stage SCLC

tumor confined to a single hemithorax and can be encompasses by a single radiation field

extensive stage SCLC

tumor extends beyond a single radiation field

treatment overview of limited stage SCLC

-cure

-improve quality of life

-radiation

-surgery

-chemo

-immunotherapy

-PCI

treatment overview of extensive stage SCLC

-prolong survival

-improve quality of life

-chemo

-immunotherapy

-PCI

recommended treatment of LS-SCLC

-chemo + radiation 4-6 cycles

-assess response

-immunotherapy for up to 2 years

PCI

prophylactic cranial irradiation

role of PCI in LS-SCLC

-patients usually have recurrence in the CNS

-reduces incidence of brain metastasis and increases 3 year survival

-recommended in patients who achieve complete response to treatment

chemo and immunotherapy regimens in LS-SCLC

-etoposide/cisplatin (EP)

-etoposide/carboplatin (EC)

followed by

-durvalumab consolidation

drug class of etoposide

topoisomerase inhibitor

MOA of etoposide

inhibits topoisomerase II, result in single and double strand breaks

adverse effects of etoposide

-myelosuppression

-N/V

-hypotension

-hypersensitivity reactions

-secondary AML