Download Recent Advances in Systemic Therapy of Lung Cancer

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.