Clinical Activity of the Oral ALK Inhibitor, Crizotinib (PF-02341066), in Patients with ALK-positive Non-small Cell Lung Cancer

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Clinical Activity of the Oral ALK Inhibitor,
Crizotinib (PF-02341066), in Patients with
ALK-positive Non-small Cell Lung Cancer

• Authors Bang Y,1 Kwak EL,2 Shaw A,2 Camidge DR,3
  Iafrate AJ,2 Maki RG,4 Solomon B,5 Ou SI,6
  Salgia R,7 Clark J2
• Reviewed by Dr. Charles Butts
• Date posted Post ASCO 2010 June 15, 2010

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Background

• Recognition of potential oncogenic drivers in
  NSLC
• EMLA4-ALK fusion gene identified in approx. 5
  adenoca lung
• Crizotinib inhibits ALK and c-met at clinically
  relevant dose levels

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First in Human Study

• Molecularly enriched cohort of 82 patients
• Positive for ALK and c-met
• Primarily pre-treated patients
• Crizotinib 250 mg p.o. BID

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Clinical and Demographic Features of Patients
with ALK-positive NSCLC
N82
Mean (range) age, years Mean (range) age, years Mean (range) age, years Mean (range) age, years 51 (2578)
Gender, male/female Gender, male/female 43/39
Performance status, n () 0 0 0 24 (29)
Performance status, n () 1 1 1 44 (54)
2 2 2 13 (16)
3 3 3 1 (1)
Race, n () Caucasian Caucasian Caucasian 46 (56)
Asian Asian Asian 29 (35)
Smoking history, n () Never smoker Never smoker Never smoker 62 (76)
Smoking history, n () Former smoker Former smoker Former smoker 19 (23)
Current smoker Current smoker Current smoker 1 (1)
Histology, n () Adenocarcinoma Adenocarcinoma Adenocarcinoma 79 (96)
Squamous Squamous Squamous 1 (1)
Other Other Other 2 (2)
Prior treatment regimens, n () 0 0 0 5 (6)
Prior treatment regimens, n () 1 1 1 27 (33)
2 2 2 15 (18)
3 3 3 34 (41)
Not reported Not reported Not reported 1 (1)
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Results

• ORR 57
• PS 2,3 57
• 3 regimens 56
• Duration of response 1-15 months
• Median PFS not reached
• 6 month progression free 72

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Grade 3/4 Toxicity ()
Grade 3 Grade 4
Any 12 1
AST elevation 1 0
Neutropenia 1 0
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STUDY COMMENTARY

• Increasing evidence of molecular profiling of
  NSCLC can help in treatment selection
• This is an early (first in human trial) but
  shows very promising results
• Minimal toxicity with mild GI disturbance in
  50 and visual changes (light dark) in 40.
• Even in heavily pre-treated patients there is
  a high response which appears to be durable.

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BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS

• Ongoing trials will determine the ultimate
  role of these agents.
• Canadian investigators/patients have the
  opportunity to participate in these trials
• Once again raises the need for adequate tissue
  samples and molecular pathology labs equipped to
  provide testing.