Lung Cancer + Basic Sciences Flashcards
Risk factors for lung cancer
• Smoking
○ Increases risk of lung ca by a factor of 10
○ Weaker association with lung adenocarcinoma
• Other factors
○ asbestos - increases risk of lung ca by a factor of 5
§ Smoking and asbestos are synergistic, i.e. a smoker with asbestos exposure has a 10 * 5 = 50 times increased risk
○ arsenic
○ Radon - 2nd leading cause of lung cancer
○ nickel
○ chromate
○ aromatic hydrocarbon
○ cryptogenic fibrosing alveolitis
• Factors that are NOT related
○ coal dust
• Family history (genetic predisposition)
• Other RF: pulmonary scarring, previous radiation, pulmonary fibrosis, chronic infections (eg: TB, HIV)
What is the most potent carcinogen in cigarette smoke?
Polycyclic aromatic hydrocarbons
Types of lung cancers
Lung cancer is divided into 2 types:
(1) Small Cell Lung Cancer 13%: central location, rapid tumour growth, early metastases and associated with numerous paraneoplastic syndromes
(2) Non-Small Cell Lung Cancer
- Adenocarcinoma (peripheral) - most common 40% and more common in women + non smokers
- Squamous cell carcinoma (central) 20%
- Large cell carcinoma 7%
Features of adenocarcinoma
- Location
- Characteristics
- Peripheral
- Most common form of lung cancer
- More common in women and non-smokers
- Associated with mutations in EGFR/ALK/KRAS gene
- Risks with pulmonary fibrosis
- Prognosis usually better than other lung cancer
- Gynaecomastia due to production of HCG (increased risk with large cell carcinoma + poorly differentiated adenocarcinoma)
- Increased risk with adenocarcinoma: thrombophlebitis migrans, nonbacterial verrucous endocarditis
Features of squamous cell carcinoma
- Location
- Characteristics
- Location: central “sentrally located”
- Strong associations with smoking
- Cavitations
- Cavitary lesions arising from hilar bronchus
- PThrP: hypercalcemia
- Histology: Intercellular bridges (desmosomes)
Keratin pearls
C; central location, hypercalcemia, cavitations
Features of large cell carcinoma
- Location
- Characteristics
- Location: peripheral
- Poor response to chemotherapy
- Early mets
- Poor prognosis
Features of small cell lung cancer
- Location
- Features
- Location: central
- Strong association with SMOKING-almost all cases are in smokers
- Very CHEMOTHERAPY SENSITIVE
- Associated with several PARANEOPLASTIC syndromes
• Cushing syndrome
• SIADH
• Lambert Eaton Syndrome: ab against voltage gated calcium channels - Undifferentiated and very aggressive with early metastases
- Associated mutations: L-myc oncogene
- Classically bulky lymphadenopathy
- Chemo+ radiosensitive
- Doesn’t cause clubbing
- CNS METS FREQUENT - MRI BRAIN
Staging of SCLC
Only 2 stages: limited and extensive
Limited: disease in one haemothorax and ipsilateral mediastinal nodes, encompassable by a single radiation field
Extensive: anything that’s not limited
Treatment for SCLC
LIMITED
- Curable (20-30%) with concurrent chemoradiation (CISPLATIN + ETOPOSIDE) and PCI (prophylactic cranial irradiation) in responders as brain is a brain sanctuary site for micromets
EXTENSIVE
- Generally incurable
- BUT expect excellent response with chemo/RT even in very unwell patients
- Median survival 12 months with chemoimmunotherapy
Chemotherapy (CARBOPLATIN + ETOPOSIDE) + ATEZOLIZUMAB (PDL1 inhibitor) improved PFS + OS
Features of mesothelioma
- Asbestos and tobacco related 10-20x risk of mesothelioma Asbestos risk of NSCLC - especially squamous cell carcinoma - Long latency (30-40 years) - Usually pleural or peritoneal
Epitheloid more common but sarcomatoid has worse survival
Tx:
- Generally incurable, role of surgery + radio is limited
- Radical Tx: extrapleural pneumonectomy
- Palliative chemo improves survival: cisplatin + pemetrexed
Nivolumab + ipilimumab in unresectable malignant pleural mesothelioma
Pancoast tumour
• Apical lung carcinoma
• Superior sulcus tumour
• Predominantly NSCLC
• May lead to the development of Pancoast Syndrome: constellation of symptoms secondary to the mass effect of the tumour on surrounding structures
○ Cervical sympathetic ganglion (stellate ganglion): Horner syndrome (ipsilateral miosis - small pupil), ptosis, anhidrosis)
○ Brachial Plexus: localised pain in the axilla and shoulder (plexus neuralgia)
- Upper limb motor and sensory deficits (eg: hand muscle weakness and atrophy) - wasting hand muscles (T1)
○ Recurrent laryngeal nerve: hoarseness
○ Brachiocephalic vein
- Unilateral oedema of the arm
- Facial swelling
○ Phrenic Nerve: paralysis of the hemidiaphragm (visible as elevated hemidiaphragm on CX
NOTE:
The right and left recurrent laryngeal nerves are not symmetrical, with the left nerve looping under the aortic arch, and the right nerve looping under the right subclavian artery then traveling upwards.
What are the common sites of metastsis for lung cancer?
Lung cancer loves to BLAB
- Brain
- Liver
- Adrenals
- Bone
Paraneoplastic syndromes of lung cancer
Shared paraneoplastic features
- Cachexia
- Thrombocytosis + DIC
- Hypercoagulability
- Dermatomyositis
- Acanthosis negricans
NSCLC
- Hypercalcaemia of malignancy - increased risk with squamous cell
- Gynaecomastia due to production of HCG (increased risk with large cell carcinoma + poorly differentiated adenocarcinoma)
- Hypertrophic osteoarthropathy
- Increased risk with adenocarinoma: thrombophlebitis migrans, nonbacterial verrucous endocarditis
SCLC
- Cushing syndrome
- SIADH
- Lambert eaton syndrome
- Paraneoplastic cerebellar degeneration
- Peripheral neuropathy
Clinical features of lung cancer
• Pulmonary Symptoms:
- Cough, haemoptysis
- Progressive dyspnoea
- Wheezing
- Chest pain
• Extrapulmonary Symptoms
- Constitutional symptoms - weight loss, fever, weakness
- Signs and symptoms of tumour infiltration and/or compression of neighbouring structures
SVC syndrome: impairs venous backflow to the right atrium, resulting in venous congestion in the head, neck and upper extremities
Treat with steroids
Common in SCLC
Hoarseness: paralysis of the recurrent laryngeal nerve
Dyspnoea and diaphragmatic elevation: paralysis of the phrenic nerve
Dullness on percussion + reduced breath sounds: malignant pleural effusion on the affected side
Dysphagia: oesophageal compression
What should you be concerned about if a patient >40yo has recurrent respiratory infections (eg: pneumonia ) in the same pulmonary region?
Lung cancer
Investigation for lung nodule
- <5mm: no follow up if malignancy risk is low
If high to consider serial CT scans - 5-7mm: Serial CT scans
- > 8mm: PET or biopsy
If suspicious for malignancy - resection!
Diagnosis for lung cancer
- Central endobronchial lesions: bronchoscopy
- Peripheral lung lesions: radiology guided core biopsies
- Central nodes: EBUS (endobronchial US)
Diagnosis: morphology + immunohistochemistry/molecular testing
- TTF-1 and Napsin A +ve for adenocarcinoma (TANA)
- Non squamous NSCLC (adenocarcinoma/large cell): EGFR, ALK, ROS1
- PDL1 expression for all NSCLC (squamous, adeno, large cell)
Imaging for lung cancer
- If CXR raises suspicion –> CT scan
- PET to stage mediastinum and identify metastatic disease if curative intent is planned for NSCLC
- Isolated PET positive findings require histological confirmation
- PET not sensitive for brain - requires ideally MRI Brain
Staging for NSCLC and basic treatment
Stage 1: No nodal involvement
- Surgical resection if medically fit - lobectomy vs pneumonectomy
Lobectomy with mediastinal LN dissection is recommended for tumours >2cm
- Stereotactic radiation if non surgical candidate
Stage 2 A+B: Ipsilateral peribronchial and/or hilar LN and intrapulmonary nodes
- Surgical resection + adjuvant chemo
Stage 3A: ipsilateral mediastinal and/or subcarinal LN
Stage 3B: contralateral mediastinal, hilar, supraclavicular LN
- Resectable: neoadjuvant chemo + surgical resection
- Unresectable: concurrent chemoradiation and DURVALUMAB (PDL1) for 12 months
Stage 4: metastatic disease including malignant pleural effusion + contralateral lung nodules
- Palliative systemic therapy - chemotherapy, targeted therapy and immunotherapy
+ palliative RT
Adjuvant Chemo
- Consider for all fit stage II-III patients post resection
- No conclusive benefit for stage IV
- Generally 4 months of cisplastin + venorelbine
What are the driver mutations in non squamous cell carcinoma (adenocarcinoma, large cell)?
Who should be tested?
Driver Mutations in NSCLC - EGFR - ALK - ROS (EAR)
Who should be tested?
- All lung ADENOCARCINOMAS
- All carcinomas with a component of adenocarcinoma, eg: adenosquamous carcinoma
- Large cell carcinoma
- Never smokers with squamous cell carcinoma
Driver mutations are absent or extremely rare in
- Pure squamous cell carcinoma
- Classic small cell lung cancer
- Large neuroendocrine carcinoma
Stage IV targeted therapies for lung cancer
Factors to Consider
- Presence of driver mutations: EGFR, ALK rearrangements, ROS 1
- Presence of PDL-1
- Squamous vs Non squamous (squamous more aggressive and no therapy available)
- ECOG
- RT for palliation + brain mets
EGFR TKIs
- Erlotinib
- Gefitinib
- Afatinib
- Osimertinib for T790M +ve
ALK TKIs
- Crizotinib
- Alectinib
ROS 1 TKI
- Crizotinib,
- Entrectinib
EGFR mutations
Osimertinib - 1st line - For T790M +ve patients - 3rd gen - Wouldn't give if non exon 19/L85*R Gefitinib, Erlotinib - 1st gen Afatinib - 2nd gen
- Most common EGFR activating mutations
Exon 19 deletion
Exon 21 point mutation L858R
More common in :
- Non smokers
- Females
- Asian ethnicity
- Adenocarcinoma
For patients with EGFR mutation, more effective than chemo
Side effects of EGFR inhibitors
Osimertinib, Gefitinib, Afatinib
- Acneform rash - presence of rash is correlated with response to therapy. Treat with topical or oral abx (tetracyclines), topical steroids, skin care, sun protection - Diarrhoea - Macular oedema - Alopecia - Nail changes - Pulmonary toxicity Don't cause cytopenia
EGFR inhibitor resistance
- Progression due to resistance common after 6-24 months
- 60% due to T790M resistance mutation
- Osimertinib (3rd gen EGFR TKI) highly active
Osimertinib
- MOA
- Indication
- SE
MOA: EGFR inhibitor
- 3rd gen irreversible EGFR-TKI
- Selectively inhibits both EGFR TKI and EGFR T790M resistance mutations
- Excellent CNS penetration
SE
- Skin toxicity (less skin toxicity than others)
- DIarrhoea
- pneumonitis
- Cardiac impairment - more prolonged QT
ALK Mutations - anaplastic lymphoma kinase translocation
ALECTINIB is 1st line
- Fusion oncogene EML4-ALK
- Inversion in Chromosome 2P that fuses EML4 gene with ALK gene
Occurs in:
- Adrenocarcinoma
- Non smokers
- Younger patients
- Crizotinib: 1st gen
- Alectinib: 3rd gen, improved 1st line DFS and better CNS penetration than crizotinib
- Lorlatinib: 2nd gen TKI failure
Following progression with an ALK inhibitor other than crizotinib
ALECTINIB is 1st line - less toxic, better CNS respones
SE:
- Hypercholesterolemia
- Hypertriglyceridemia
- Cognitive and mood effects
- Visual changes
- Neutropenia
- Fluid retention
- Prolonged QT
ROS1 Rearrangement
- Occur in adenocarcinoma, non squamous NSCLC
Tends to occur in:
- Younger patients
- Non smokers
Respond to crizotinib (1st line), lorlatinib, entrectinib
KRAS G12C mutation
KRAS mutation NSCLC
- Occurs in 15-30% of lung adenocarcinomas
Common in
- Smokers
Western background
Sotorasib for KRAS
If there is no driver mutation - treatment
Stage 3B NSCLC: consolidation DURVALUMAB
Stage 4 Wildtype NSCLC
- Check PDL1 levels
- PDL 1> 50%: prembolizumab single agent
- PDL1 < 50% - prebolizumab + platinum + pemetrexed
Stage IV non small cell lung cancer with PDL1:
Platinum Doublet + PD1 or PDL1 inhibitors
<50
- Pembrolizumab + Chemo
- Atezolizumab + bevacizumab + chemo for non squamous cell cancer only
- Nivolumab + Ipilimumab with chemo for squamous cell cancer only
> 50
- Pembrolizumab as single agent (preferred)
- Pembrolizumab with chemo
- Atezoliumab + bevaciziumab + chemo for non squamous cell cancer
- Platinum Doublet: cisplatin + etoposide or cisplatin + vinorelbine)
- Note: pemetrexed (non squamous NSCLC)
PD1 Inhibitors: Nivolumab, Prembolizumab
PDL1 Inhibitors: Atezolizumab, Durvalumab
General treatment for NSCLC
Stage 3: Consolidation durvalumab
Stage 4:
- PD1/PDL1 antibody for everyone is first line if wildtype with no contraindications
- Monotherapy or in combination with chemo depends on PDL1
- Generally doses work well in EGFR/ALK mutated patients
Systemic therapy for locally advanced and metastatic non small cell lung cancer.
- EGFR mutations: Osimertinib
- ALK rearrangements: Alectinib or Brigatinib
- ROS1 rearrangements: Crizotinib
- BRAF V600E mutations: Dabrafenib + trametinib
- NTRK alterations: Larotrectinib
PDL 1 score
- > 50%: Pembrolizumab as single agent
- <50% Prebolizumab + platinum + pemetrexed
Mechanism of action of EGFR inhibitors with respect to cell cycle
Epidermal growth factor inhibitors (EGFRi) such as erlotinib (used in nonsmall cell lung cancer) and cetuximab (used in colorectal cancer and head/neck cancer) block the progression of a cell from the G1 phase to the S phase.
Features of the cell cycle
The cell cycle can be divided into two phases: interphase and mitosis.
Interphase is further divided into the G1 (gap 1), S (synthesis), and G2 (gap 2) phases, which prepare the cell for division.
- G1 Phase: proteins and cell organelles are synthesized. - S Phase: DNA is replicated in the S phase.
- G2 Phase: DNA replication errors are repaired.
- Mitosis (M) or cell division.
- There are various checkpoints within the cell cycle that ensure the cell is ready to enter the next phase (G1, G2, and M checkpoints).
- Only proliferating cells pass through the cell cycle.
- Most mature tissue cells are in a resting phase, the G0 phase.
- These cells are differentiated, with each performing a specific function.
- Mature differentiated cells do not divide
Predictive vs prognostic biomarker
PREDICTIVE: provides information on OUTCOME with regards to SPECIFIC THERAPY
PROGNOSTIC: provides information on OUTCOME, INDEPENDENT OF THE THERAPY that is used
PREDICTIVE BIOMARKER: identify subgroups most likely to respond
- provides information on the probability of obtaining a response to treatment
- Allows for therapeutic decisions
- EG:
HER2/EGFR –> predicts will respond to treatment
KRAS mutated –> predicts resistance to treatment
PDL1 >50% –> predicts better response to immunotherapy
BRAF in melanoma is PREDICTIVE not prognostic of response to BRAF inhibitors
PROGNOSTIC BIOMARKER: provides information on course of disease
- informs about a likely cancer outcome (eg, disease recurrence, disease progression, death) independent of treatment received.
- reflects the underlying biology and natural history
- treatment benefit similar for biomarker-positive and biomarker negative patient, but the biomarker will still be associated with a differential outcome depending on whether it is present or absent
- the biomarker positive patients have a better survival than biomarker negative patients, independent of treatment group
EG: EGFR IN LUNG CANCER
Hallmarks of Cancer
- Evading growth suppressors
- Cyclin dependent kinase inhibitors, eg: CK 4/6 inhibitors in breast cancer - Avoid immune destruction
- AntiCTLA-4 mAB - Enabling replicative immortality
- Telomerase inhibitors - Tumour promoting inflammation
- Selective anti-inflammatory drugs - Activating invasion and metastasis
- Inhibitors of HGF-c-Met - Inducing angiogenesis
- Inhibitors of VEGF signalling - Genome instability and mutation
- PARP inhibitors - Resisting cell death
- Proapoptotic BH3 mimetics - Deregulating cellular energetics/ epigeneitcs
- Aerobic glycolysis inhibitors - Sustaining proliferative signalling
EGFR inhibitors
Side effects of immunotherapies
- Related to autoimmunity - immune checkpoint blockade enhances T cell responses throughout the body
- Can occur anywhere in the body
- Thyroid dysfunction: hypothyroid> hyperthyroid
- Pneumonitis - steroids, if worsening hypoxia will require infliximab or mycophenolate
- Colitis - more common in CTLA4 >PD1
- Renal dysfunction
- Hepatotoxicity
- PD1: Thyroid, lung, autoimmune diabetes
- CTLA4: Colitis, rash, hypophysitis
- SE occur normally within 4-12 weeks
- Endocrinopathies can occur anytime
- Can also occur after medications are ceased
What is pseudoprogression/hyperprogression
Immunotherapy - the following are exclusive to immunotherapy
- Pseudoprogression: immune storm, tumour site increases in size - Hyperprogression: tumour growth increases significantly
How do you treat colitis which has occurred secondary to immunotherapy?
CTLA4 > PD1
G1: <4 stools more than baseline - LOPERAMIDE
G2: 4-6 stools more than baseline
WH immunotherapy
Add IV methpred and then taper with oral or can start with oral
G3: >7 stools more than baseline
WH immunotherapy
IV pred
If refractory over 3-4 days - add infliximab
G4: perforation
Permanently discontinue immunotherapy
Add IV methylpred
Infliximab and surgical review
Mutations associated with
- Colorectal cancer
- Lung cancer
- Melanoma
- Breast cancer
- Colorectal Cancer: EGFR overexpressed in ~80% –> KRAS wild type/not mutated
- Lung Cancer:
EGFR 10-30%
KRAS pG12C mutations - Melanoma
BRAF in 50% - Breast Cancer
HER2
Which group of individuals are EGFR mutations more likely to be found?
Non smoker
Female
Asian
Adenocarcinoma
How do you manage diarrhoea in
- chemotherapy
- targeted therapy
- immunotherapy
Chemotherapy
- Infection screen + IVF
- Loperamide
- Codeine
- Octreotide infusion
- Neutropenic colitis ?abx
- C difficle
Targeted Therapy
- Infection screen + IVF
- WH medication + Loperamide
Immunotherapy - Infection screen + IVF - Grade 1-2 : oral steroids - Grade 3: IV steroids - Colonoscopy - Infliximab Think colitis for immunotherapy
Side effects of the following chemotherapy
- Taxanes: paclitaxel (breast), oxaliplatin (bowel), docetaxel (prostate)
- 5FU/Capecitabine
- Anthracyclines: doxorubicin (breast), epirubicin
- Alkylating agents: temozolamide, ifosfamide
- Vinca alkaloids: vincristine
Topoisomerase I inhibitors: Irinotecan (bowel)
- Taxanes: paclitaxel (breast), oxaliplatin (bowel), docetaxel (prostate)
Peripheral neuropathy
Paclitaxel: hypersensitivity infusion reactions - 5FU/Capecitabine
Diarrhoea
Hand/foot syndrome - Anthracyclines: doxorubicin (breast), epirubicin
Cardiotoxicity
Chemo induced N+V - Alkylating agents: temozolamide, ifosfamide, cyclophosphamide
Ovarian insufficiency
Nausea
Thrombocytopenia
IFOS - encephalopathy - treat with methylene blue
Mesna always given with ifosfamide to protect bladder and prevent irritation and bleeding. - Vinca alkaloids: vincristine
Peripheral neuropathy
Topoisomerase I inhibitors: Irinotecan (bowel)
Diarrhoea
Metastatic testicular cancer chemo treatment and side effect
BEP
- Bleomycin: pneumonitis, ILD
- Etoposide
- Cisplastin: peripheral neuropathy, tinnitus, N+V, renal impairment/electrolyte derangement
Pathophysiology of chemotherapy induced N+V involves activation of neurotransmitters in the brain. What is the receptor for substance? A. H-hydroxytryptamine-3 B. Dopamine 2 C. Gamma aminobutyric acid A D. HIstamine 1 E. Neurokinin 1
E. Neurokinin 1
MOA of the following anti-emetics
- Metoclopramide
- Ondansetron/Palonestron
- Aprepitant
- Targin
- Cyclizine
- Metoclopramide: D2 antagonist
- Ondansetron/Palonestron: 5HT3
- Aprepitant: Neurokinin 1
- Targin: reduces opioid associated constipation without reducing opioid effiaccy
- Cyclizine: H1 antagonist, anticholinergic action
What is chromogranin A a marker of ?
Neuroendocrine tumours
What is the most common SE for immunotherapy?
Most common toxicities: skin toxicities
Most common significant or serious toxicities: GI toxicity
Endocrinopathies associated with immunotherapy
Pituitary Gland
- Hypophysitis
- ACTH decrease
- Secondary adrenal insufficiency
Thyroid Gland
- Hyperthyroidism
- Hypothyroidism
- TSH increase or decrease
- Thyroiditis
- Free thyroxine increase or decrease
- Autoimmune thyroiditis
Adrenal glands
- Primary adrenal insufficiency
Pancreas
- Diabetes
What does the following biomarkers predict:
HER2 amplication
KRAS mutation
HER2 amplication predicts response to trastuzumab
KRAS mutation in colorectal cancer predicts lack of response to cetuximab (EGFRI) - only works for wild type KRAS
What cancers are the following VEGF receptor inhibitors used for?
- Sorafenib
- Sunitinib, pazopanib, cabozantinib
- Lenvatinib, vendetanib
- Sorafenib: HCC, thyroid, clear cell RCC
- Sunitinib, pazopanib, cabozantinib: clear cell RCC
- Lenvatinib, vendetanib: radio-iodine refractory differentiated thyroid
EGFR Inhibitors
- EGFR (mab)
- EGFR (TKI)
- EGFR - activity against T790M
EGFR (mab)
- Cetuximab/Panitumumab
- CRC (KRAS WILD TYPE)
- Head and Neck SCC
EGFR (TKI)
- Erlotinib, Gefitinib, Afatinib
- NSCLC EGFR +
EGFR - activity against T790M
- Osimertinib
- NSCLC EGFR T790M +
- SE: more prolonged QT
SE:
EGFR = rash, diarrhoea
HER2 inhibitor
- HER2 (MAB)
- HER2/EGFR (TKI)
- HER2 (ADC)
HER2 (MAB)
- Trastuzumab, Pertuzumab
- Breast cancer HER 2+
- Cardiotoxicity, diarrhoea (Pertuzumab)
HER2/EGFR (TKI)
- Lapatinib
- Breast cancer HER2+
- Rash diarrhoea, cardiotoxicity
HER2 (ADC) - antibody drug conjugate
- T-DM1: trastuzumab emtansine
- Thrombocytopenia, transaminitis
ALK rearrangement inhibitors
- Alectinib, Certinib, Crizotinib
- NSCLC ALK+
SE
- N+V
- Diarrhoea
- Visual disturbance
- Hepatitis
- Pneumonitis
- Bradycardia
- Alectinib - better tolerated than crizotinib and now new standard of care
BRAF inhibitors
- Dabrafenib, Vemurafenib
- BRAF TKI
- Melanoma BRAF V600E+
SE:
- Fever
- Skin: secondary cutaneous malignancies, hyperkeratosis, rash, photosensitivity
- Skin toxicities improved if given with MEK inhibtor
- Hair changes
- Arthralgia
MEK inhibitor
- Trametinib, Cobimetinib
- Melanoma BRAF V600E inhibitor
SE:
- Rash
- Diarrhoea
- Peripheral oedema
- Fever
- Retinopathy
VEGF inhibitor
VEGFR inhibitor and multi-kinase TKI
VEGF inhibitor: bevacizumab for CRC
VEGFR inhibitor: sunitinib, axitinib
Hypertension, hand-foot syndrome, diarrhoea, hypothyroidism, hepatitis, cardiotoxicity
cKIT (TKI)
Imatinib
GIST tumour
SE
- Muscle cramps
- Maculopapular rash
- N+V
- Diarrhoea
- Fatigue
Everolimus
- mTOR
- Breast Cancer ER+PR+
Pancreatic NET
Clear Cell RCC
SE
- Mucositis
- Diarrhoea
- Fatigue
- Hyperglycaemia
- Rash
- Pneumonotis
- Myelosuppression
CDK4/6 inhibitor
Ribociclib
Breast cancer ER+PR+
SE:
- Neutropenia
- Diarrhoea
- Transaminitis
PARP inhibitor
Olaparib
BRCA1/2 germline mutation +
Serous ovarian cancer
SE: N/V Diarrhoea Fatigue Taste/smell changes Myelosuppresion
