Download Recent Advances in Systemic Therapy of Lung Cancer

Survey
yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the work of artificial intelligence, which forms the content of this project

Document related concepts
no text concepts found
Transcript
Amin Kay MD FRCPC
Windsor Regional Cancer Center
CME Support from
 Boehringer Ingelheim
 AstraZeneca
 Amgen
Canadian Cancer Statistics 2014
Small Cell
Lung Cancer
Adenocarcinoma
Non-Small Cell
Squamous Cell
Carcinoma
Large Cell
Carcinoma
STAGE 4
Chemotherapy
Targeted Therapies
PD1 – PDL1 Pathway

Anti-PD1 Antibody

Improves survival
Borghaei NEJM 2015
Borgahei NEJM 2015

Overall well-tolerated

Autoimmune inflammation of any organ
◦ Managed with steroids and holding the drug
Ou. Crit Rev Oncol Hematol 2012;83:407-21
ALK
3%
BRAF PIK3CA
Other
3%
3%
3%
EGFR
23%
Undetected
KRAS
40%
25%
Other: MET amplifications 2%; HER2 1%; MEK1 0.4%; NRAS 0.2%
Kris et al. J Clin Oncology 2011;29:CRA7506



Non-Smoker
Female
Asian
UP TO
Squamous: Only 1%, so don’t bother checking.
1%
3% 2% 2%
1%
0%
0%
Exon 21,
N=13
L858R
40%
1% 0%
1%
Del 19
L858R
Exon 20 ins
Exon 19
L858R +
deletions
T790M
L861Q
49%
G719X
Pao et al. PNAS 2004;101:13306-11 Sequist et al. Presented at the 2012 Multidisciplinary Symposium in Thoracic Oncology, Chicago, IL; Sept 6-8
Can anyone name a first line EGFR inhibitor used in lung cancer?
GEFITINIB
ERLOTINIB
AFATINIB
Once daily pills
Response ~ 1 year
Survival:
~2 years vs 1 year
“…patients with NSCLC who are
being considered for first-line
therapy with an EGFR TKI…
should have their tumor tested
for EGFR mutations to determine
whether an EGFR TKI or
chemotherapy is the appropriate
first-line therapy.”
PCR
Keedy et al. J Clin Oncol 2011;29:2121-7
GEFITINIB
CT scans before and after erlotinib therapy.
Pan M et al. (2007) CNS response after erlotinib therapy in a patient with metastatic NSCLC with an EGFR
mutation Nat Clin Pract Oncol 4: 603–607 doi:10.1038/ncponc0931
ERLOTINIB
AFATINIB
•
•
•
•
Irreversible
More targets (EGFR subtypes)
More potent
More toxic
AFATINIB
GEFITINIB
LUX-LUNG 7
Resistance develops within ~10 months
OSIMERTINIB
Janne NEJM 2015
ROCILETINIB
Sequist NEJM 2015
• Moisturizer
• Minimize sun, Sunscreen
• Hydrocortisone 2.5% BID
• Clindamycin 1% BID
• Minocycline 100mg BID
Correlation
between rash
severity and
response
• If severe: hold TKI, resume at lower dose
Hirsh. Curr Oncol 2011;18:126-38







Inflammation/Infection of nail folds
Avoid trauma, wear gloves when
working with hands
Emollient lotion
Topical antibiotics (eg. Clinda 1%)
Topical Steroid (Clobetasol)
Vinegar Soak
If severe:
◦ Oral Doxycycline
◦ Silver nitrate
◦ Removal of nail Plate
• http://www.oncolink.org/experts/article.cfm?id=250
• Melosky & Hirsh, Frontiers in Oncology, 2014






Thinning
Change in colour (Re-pigmentation)
thickness
Curling
Fragility
Eyebrows and lashes too

Soft non-irritating foods

Soft Toothbrush



Normal saline or Sodium
Bicarb (baking soda) rinse
Miles Solution (steroid,
lidocaine, nystatin)
Assess for thrush and
herpes


GI tract epithelial cells
express EGFR
Secretory diarrhea



Assess for other causes (laxatives, antibiotics, Stool Cx
/ C.diff, …)
Assess volume status, electrolytes
Diet Modification:
◦ BRAT diet
◦ Avoid milk products, fatty/spicy foods

Keep hydrated

Loperamide

Admit to Hospital

IV Hydration, Electrolyte repletion

Continue Imodium

Consider Octreotide

Rule out other causes (eg. C.diff, Imaging, Scope)

Hold drug
◦ Restart at lower dose when improves to grade 1.
◦ Watch out for flare when holding TKI.
ALK
3%
BRAF PIK3CA
Other
3%
3%
3%
EGFR
23%
Undetected
KRAS
40%
25%
Other: MET amplifications 2%; HER2 1%; MEK1 0.4%; NRAS 0.2%
Kris et al. J Clin Oncology 2011;29:CRA7506
FISH
CRIZOTINIB
Visual effects:
• Visual persistence (trailer), halos
• Self-limited, no intervention required
• Pneumonitis
• Bradycardia
CERITINIB
ALECTINIB
More potent, better CNS response.