Oncology 4 Flashcards
What are the five pillars of cancer care?
radiotherapy
surgery
traditional chemotherapy
precision therapy
immunotherapy
Which pillar of cancer care has a durable response in patients who respond to therapy?
immunotherapy
What is immuno-oncology?
development and delivery of therapies that improve immune response against cancer
-provides immune system with tools to recognize tumours and strengthen tumour attack
What is the goal of immuno-oncology?
restore or enhance anti-tumour immune responses
What are the side effects of immuno-oncology agents related to?
immune-related and can affect any organ
-may include colitis/diarrhea, rash, hepatitis, endocrinopathies, uveitis, nephritis
What are the types of IO therapy?
monoclonal antibodies:
-bind specific targets to cause immune responses to destroy cancer cells
adoptive T-cell transfer:
-isolates and modifies T cells from tumor for enhanced immune response against cancer cell
cytokines:
-role in normal immune response and immune system response to cancer
treatment vaccines:
-enhance immune system response against cancer cells
Bacillus Calmette-Guerin:
-weakened form of TB bacteria, used in bladder cancer to cause immune response against cancer cells
toll-like receptor agonists:
-bind toll-like receptors on immune cells to cause immune response against cancer cells
Describe how IO differs from chemotherapy and targeted therapy.
chemotherapy:
-acts directly on cancer cells that are actively reproducing
-often causes tumour cell death vs simply inhibiting tumour growth
targeted therapy:
-inactivates specific proteins in tumour cells that are involved in growth, progression, and spread of cancer
IO:
-triggers the immune system to destroy cancer cells
-considered a type of targeted therapy
What are some inhibitory receptors found on T cells?
CTLA-4
PD-1
What is an example of a CTLA-4 inhibitor?
ipilimumab
What are examples of PD-1 inhibitors?
pembrolizumab
nivolumab
What are examples of PD-L1 inhibitors?
durvalumab
atezolizumab
avelumab
What is the site of activity of CTLA-4 inhibitors?
lymph node
What is the site of activity of PD-1 inhibitors?
cancer cell
What are the indications for CTLA-4 inhibitors?
melanoma (ipi, ipi + nivo)
kidney cancer (ipi+nivo)
small cell lung cancer (ipi+nivo)
True or false: PD-1 and PD-L1 inhibitors are used for a small range of cancers
false
used for a super broad range of cancer
True or false: the current IOs are monoclonal antibodies
true
How is IO administered?
IV
What is generally done for IO toxicity?
doses are NOT reduced for toxicity, either hold or give full dose
What is the response rate to chemotherapy in metastatic melanoma?
only 1-2% of pts achieve a durable long-term response to chemotherapy, which is no longer considered as valid treatment
What was OS for metastatic melanoma prior to introduction of immunotherapy?
about 6 months
True or false: the response rate to ipilimumab for metastatic melanoma is worse than it was for chemotherapy
false
much better survival rates with ipilimumab
How was NSCLC once considered as a disease?
was once considered a single disease, until distinct subtypes, characteristics identified
-subtype characteristics are clinically relevant for treatment planning from diagnosis
What was found with the CheckMate 003 trial?
people who responded to the checkpoint inhibitor (nivo) had a long-term durable response vs cytotoxic therapy
What was found with the KeyNote-024 trial?
pembrolizumab is superior to CT in patients with TPS > 50%
Why do different forms of cancer therapies lead to different toxicities?
different MOA leads to different toxicities
Which chemotherapy-related and immune-related adverse effects tend to overlap?
NVD
fatigue
symptoms may overlap but mediated through different pathways
What happens with irAEs without appropriate management?
irAEs tend to self-perpetuate without appropriate management
What are the risk factors for irAEs?
personal/family hx of autoimmune diseases
tumor infiltration
concomitant medications and occupational exposures
What are the key factors for prevention of irAEs?
HCP and patient education
-awareness of risks of IO agents
patient reporting
-immediate reporting of signs and sx
call-back program
-regular calls to pt to assess irAEs
Describe proper irAE follow-up before and after treatment.
during IO treatment:
-lab tests before every IO administration
-compare values to baseline
after IO treatment termination:
-lab tests/evaluation on 3 month basis during 1st year and then every 6 months
True or false: irAEs can develop even after discontinuation of IO treatment
true
What are the potential etiologies of adverse effects?
disease-related
incidental event
immune-related adverse event
Which body systems might be impacted during an irAE via IOs?
skin
hepatic
gastrointestinal
renal
eye
endocrine
cardiac
pulmonary
neurologic
When do the irAEs tend to appear?
rash, pruritis: ~ 4 wks
liver: ~6 wks
diarrhea, colitis: ~5 wks
hypophysitis: ~6 wks
Describe the management of irAE according to the severity of symptoms.
grade 1:
-supportive care; +/- withhold drug
grade 2:
-withhold drug, consider restart if toxicity resolves to grade < 1
-initiate low dose steroids (prednisone 0.5 mg/kg/day or ~) if sx do not resolve within 1 week
grade 3/4:
-d/c drug
-high dose steroids (prednisone 1-2 mg/kg/day or ~) taper once grade < 1
severe or steroid-refractory:
-no response to steroids within 48-72h
-additional immune suppressive agents
What do most irAEs resolve with?
temporary or permanent d/c of IO treatment
temporary immunosuppression
How long does it take for irAEs to resolve?
depends on nature of toxicity
-immunosuppression can rapidly improve GI, hepatic, and renal toxicities
-skin and endocrine toxicities require more time for resolution
What is the impact of immunosuppression on IO efficacy?
no negative impact on treatment efficacy
What is the optimal steroid dosing regimen for irAEs?
not yet established
-prolonged, high-dose steroid use has been associated with additional risks
-confirmed risk of opportunistic infection from steroid use in irAE management
Describe proper management of steroid-related complications.
monitor for signs and sx of steroid-related AEs
antibiotic prophylaxis may be warranted
gradual steroid tapering is important
-taper over at least 1 month before resuming IO therapy
additional considerations:
-vitamin D and calcium (osteoporosis)
-PPI (gastritis)
What are the toxicities of CAR-T?
B-cell aplasia
cytokine release syndrome
-frequently begins with fever, may develop unstable hypotension and hypoxia
-potentially fatal, may require ICU care
neurotoxicity
-tremor, dysgraphia, impaired attention, speech difficulty, seizures
What is a common complication of both cancer and treatment?
thrombosis
-higher mortality among cancer pts
-2nd leading cause of death in cancer pts
What are the risk factors for cancer-associated thrombosis?
patient related
cancer related
treatment-related
Differentiate when to use LMWH or a DOAC in cancer-associated thrombosis.
LMWH preferred in pts:
-at high risk of bleeding
-with unresected GI or GU cancer
-significant DDI with DOACs
DOACs preferred in pts:
-at low risk of bleeding
-with other cancer types
-without significant DDIs
How long is duration of therapy for cancer-associated thrombosis?
initial 6 months
What is cancer related fatigue?
cancer-related fatigue is a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer tx that is not proportional to recent activity and interferes with usual functioning
What is the most commonly reported side effect of cancer treatment with chemotherapy, RT, or selected biologic response modifiers?
cancer related fatigue
14-96% of pts undergoing cancer tx and in 19-82% of pts post-tx
What generally occurs to cancer fatigue once treatment is complete?
generally improves but some fatigue may persist for months or years following tx
How is cancer related fatigue managed?
manage precipitating factor
-rarely an isolated symptom
energy conservation
exercise with moderate intensity
limit naps
reduce stress
food and water intake
use distractions
