Topic review of lung cancer เืนื้อหา 1: CA lung categories 2: Predisposing factor 3 Charactoristic 4 treatment

1. Niti Charat
MD, in trainee programme
Internal medicine department
Khon Kaen Hospital
All data in this material is based on current evidenced until December 11,2015

4. Tobacco
GeneticEnvironment

7. National lung screening trial
(NLST)
- 53454 subject, age 55-74,
- Tobacco at least 30 packyears
- Result show 20% reduction
in lung cancer mortality

11. A 50‐yr-old female with irregular cavitating
squamous cell carcinoma in the right upper lobe (arrows).

15. 2,3 | 5,7

27. First line
Second line
Third line
Maintenance
Not approved
1970 1980 1990 2000
Median
OS (mos)
12+
~ 6
~ 2-4
BSC Single-agent platinum Doublets
Bevacizumab + PC
Carboplatin*
1989
Erlotinib
Pemetrexed
2004
Docetaxel
1999
Paclitaxel
Gemcitabine
1998
Vinorelbine
1994
Docetaxel
2002
Bevacizumab
2006
Gefitinib
2003
Standard therapies
*Label does not include
NSCLC-specific indication
Pemetrexed
2008/2009
Histology-directed therapy
~ 8-10
Cisplatin*
1978
1. FDA Web site. 2. NCCN. Clinical practice guidelines in oncology. v.3.2011. 3. Schrump, et al. Non-small cell
lung cancer. In: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, PA: Lippincott Williams &
Wilkins; 2005.

28. STAGE Treatment
I A Surgery
I B Surgery Adjuvant Chemotherapy
II A Surgery Adjuvant Chemotherapy
II B Surgery Adjuvant Chemotherapy
III A Surgery Adjuvant Chemotherapy
III B Concurrent Chemotherapy Radiotherapy
IV Palliative Chemotherapy

36. Stage IV disease
histological
Squamous Platinum doublet Maintainance
Non squamous
Gene alteration
PRESENT
Targeted therapy
Gene alteration
ABSENT
Yes
Platinum doublet
+bevacizumab
maintainance
No
Platinum doublet
Maintainance

37. Results shown for cisplatin-based regimens only (11 trials) NSCLC Collaborative Group
BMJ 1995;311:899–909
100
80
60
40
20
0
Survival(%)
0 6 12 1824
Time from randomization (months)
Supportive care + CT
Supportive care

38. 0
5
10
15
20
25
30
35
Response rate (%) 1-yr survival (%)
two-drug regimens single agent
26%
13%
35% 30%
JAMA 2004; 292:470
Two-drugs: significantly increase in
both response rate and survival

39. RANDOMIZE
Cisplatin +
Paclitaxel
Cisplatin + Gemcitabine
Cisplatin +
Docetaxel
Carboplatin + Paclitaxel
N Engl J Med 2002; 346:92

40. 1.0
0.8
0.6
0.4
0.2
0
0 5 10 15 20 25 30
Time (months)
Cisplatin/paclitaxel
Cisplatin/gemcitabine
Cisplatin/docetaxel
Carboplatin/paclitaxel
OSestimate
Schiller, et al. NEJM 2002
Median survival time ~ 8 months
• Overall RR~19%
• 1-yr survival~33%

41. * Non-squamous=adenocarcinoma, large cell carcinoma, and other/indeterminate NSCLC histology
Non-squamous* (n=1252) Squamous (n=473)
Pemetrexed + cisplatin
Median OS: 11.0 mos
Gemcitabine + cisplatin
Median OS: 10.1 mos
HR=0.844
(95% CI: 0.74–0.96)
P=0.011
Pemetrexed + cisplatin
Median OS: 9.4 mos
Gemcitabine + cisplatin
Median OS: 10.8 mos
HR=1.229
(95% CI: 1.00–1.51)
P=0.051
Survival Time (months) Survival Time (months)
100
90
80
70
60
50
40
30
20
10
0
SurvivalProbability(%)
100
90
80
70
60
50
40
30
20
10
0
SurvivalProbability(%)
Ciuleanu, et al. ASCO 2008

42. TS
• SCLC – High TS
• Squamous – High TS
• Adeno – Low TS
Bhattacharjee PNAS 2001

44. Recombinant
humanized
monoclonal
antibody to
VEGF-A

45. R
A
N
D
O
M
I
Z
E
Paclitaxel 200 mg/m2 IV
Carboplatinum AUC 6 q 21d
X6 cycles
Paclitaxel 200 mg/m2 IV +
Carboplatinum AUC 6 q 21d
X6 cycles
Bevacizumab 15mg/kg q3 wk
til PD
Stratification by:
• Stage (IIIB or IV)
• Geographic region
Sandler. NEJM 2006; 355: 2542
IIIB and IV non-squamous
No brain mets
No hemoptysis
No prior chemotherapy

46. HR: 0.79, 0.67-0.92
P = .003
Pac/carbo + bev, n=434 51% 23%
Pac/carbo, n=444 44% 15%
0.0
0.2
0.4
0.6
0.8
1.0
Proportionsurviving
0 6 42 4818 30
12 mo 24 mo
12 24 36
Months
12.3
10.3
Sandler AB, et al. New Engl J Med. 2006;355:2542-2550.
~37% of patients with advanced NSCLC are eligible to receive bevacizumab, <20% if also exclude age ≥70 years
Non-Squamous histology, no hemoptysis, brain metastases

47. PC
n=427
PCB
n=420
Hemorrhage
Hemoptysis 0 5
GI Bleed 1 2
Neutropenic Fever 1 5
CNS 0 2*
Pulmonary Embolus 0 1
Total 2 15
Sandler AB, et al. New Engl J Med. 2006;355:2542-2550.

53. Limited disease
(within a tolerable radiation field)
Extensive disease
(distant metastases)

55. Ki – 67

57. Limited disease
Etoposide + cisplatin or carboplatin (4-6
cycle)
CCRT start with first or second cycle (twice
daily to 4500 cGy or once- daily to 6300
cGy
Extensive disease
Etoposide + cisplatin or carboplatin
(4-6 cycle)
Complete /partial response
• PCI
• Observe progression with CT
• Smoke cessation
• If no evidence of dz, >3yr,
surveillance for secondary primary
Progression
Refractory
Topotecan
CAV
Paclitaxel
Docetaxel
Irinotecan
Gecitabine
Temozolomide
Vinorelbine
Supportive care
Sensitive
Topotecan
CAV
Re-challence first line
reg. if initial response
>6month

59. Does PCI have a role in patients with
ED-SCLC after chemotherapy?

60. Study Design
PCI
20-30 Gy in
5-12 fractions
No PCI
RandomAny response
Stratification: Performance score and Institute
< 5 weeks
4-6 weeks
No response
Chemotherapy
(4-6 cycles)
Slotman et al. NEJM 2007

61. (months)
0 4 8 12 16 20 24 28 32 36
0
10
20
30
40
50
60
70
80
90
100
PCI
Control
1 year: 14.6% vs. 40.4%
HR: 0.27 (0.16-0.44) p<0.001
Symptomatic brain
metastases

62. (months)
0 4 8 12 16 20 24 28 32 36
0
10
20
30
40
50
60
70
80
90
100
P=0.2699
Control
PCI
Extracranial progression

63. (months)
0 3 6 9 12 15 18 21 24 27
0
10
20
30
40
50
60
70
80
90
100
PCI
Control
6 months: 23.4% vs. 15.5%
HR: 0.76 (0.59-0.96) p=0.02
Failure-free survival

64. (months)
0 4 8 12 16 20 24 28 32 36
0
10
20
30
40
50
60
70
80
90
100
PCI
Control
1 year: 27.1% vs. 13.3%
HR: 0.68 (0.52-0.88) p=0.003
Overall survival