Download Incidence and Mortality of Lung Cancer in US, 2007

Incidence and Mortality of Lung Cancer in US, 2007

Life-long risk of lung cancer: 1:12 for men; 1:16 for women
– Closely correlates with smoking patterns
Overall
Men
Women
Annual incidence
213,380
114,760
98,620
Annual mortality
160,390
89,510
70,880




Leading cause (29%) of cancer deaths
More deaths from lung cancer than from prostate, breast, and
colorectal cancers combined
5-year survival rate (all stages): 16%
Although mortality has decreased slightly, mostly in men, incidence is still
rising in both genders
Jemal A, et al. CA Cancer J Clin. 2007;57:43.
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TNM Staging of NSCLC
Stage IA
T1
N0
M0
Stage IB
T2
N0
M0
Stage IIA
T1
N1
M0
Stage IIB
T2
T3
N1
N0
M0
M0
T = primary tumor; N = nodal involvement; M = distant metastasis.
Mountain CF. Chest. 1997;111:1710.
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TNM Staging of NSCLC (cont’d)
Stage IIIA
T1–3
T3
N2
N1
M0
M0
Stage IIIB
T4
Any T
Any N
N3
M0
M0
Stage IV
Any T
Any N
M1
T = primary tumor; N = nodal involvement; M = distant metastasis.
Mountain CF. Chest. 1997;111:1710.
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Lung Cancer Histology


NSCLC
– 80%–85% of all
lung cancers1
– NSCLC types:
squamous cell,
adenocarcinoma,
large cell
SCLC
– 15% of all lung
cancers2
– Incidence declining
Small Cell3
15%
Squamous Cell3
25%–30%
Large Cell3
10%–15%
Adenocarcinoma3
40%
1. http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf.
2. http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf.
3. http://www.cancer.org/docroot/CRI/content/CRI_2_2_1x_What_Is_Non-small_Cell_Lung_Cancer.asp
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5-Year Survival with Lung Cancer in the US
Limited SCLC
Extensive SCLC
Stage IA NSCLC
Stage IB NSCLC
Stage IIA NSCLC
Stage IIB NSCLC
Stage IIIA NSCLC
Stage IIIB NSCLC
Stage IV NSCLC
Actual (%)
15–25
<1
70–85
60–70
35–45
25–35
5–20
3–7
<1
Target (%)
25–30
2–5
85–95
70–85
45–60
35–45
20–30
10–20
2–5
DeVita Jr VT, Hellman S, Rosenberg SA, eds. Cancer of the Lung. In: Cancer: Principles & Practice of
Oncology. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005;chap 31.
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Limited SCLC
Combination Chemotherapy and RT


EP chemotherapy combined with concurrent chest RT is well
studied in limited disease
Little treatment-related mortality
Coop Group
Comparison
Regimen(s)
JCOG1
NCI-C2
Concurrent vs sequential
Early vs delayed concurrent
EP/RT > EPRT
CAV/EP/RTC2 >
CAV/EP/RTC6
EP/BID RT (45 Gy) >
EP/QD (45 Gy) RT
ECOG/RTOG3 BID vs QD concurrent
5-Year
Overall Survival (%)
24 vs 18
20 vs 10
26 vs 16
CAV = cyclophosphamide/doxorubicin/vincristine; EP = etoposide/cisplatin; RT = radiation therapy.
1. Takada M, et al. J Clin Oncol. 2002;20:3054. 2. Murray N, et al. J Clin Oncol. 1993;11:336.
3. Turrisi AT, et al. N Engl J Med. 1999;340:265.
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SCLC Standard Therapy
Limited Stage




EP (4 cycles)
Concurrent chest RT
PCI for CR
Clinical trials
Extensive Stage




EP (IP) or EP/CAV (4–6 cycles)
CNS metastases: chemotherapy
or RT
Bone metastases or obstructing
lesions: RT
“Window of opportunity” clinical
trials
EP = etoposide/cisplatin; RT = radiation therapy; PCI = prophylactic cranial irradiation;
CR = complete responder; IP = irinotecan/cisplatin; CAV = cyclophosphamide/doxorubicin/vincristine.
Courtesy of Corey L. Langer, MD.
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Current Treatment Options for NSCLC
Treatment
Algorithm
for NSCLC
Stage I
(Localized
Disease)
Stage II
(Localized
Disease)
Surgery
Adjuvant Treatmenta,b
Radiation Therapy
(If Unsuitable
for Surgery)
a. Adjuvant therapy for stage IB is controversial.
b. Post hoc subgroup analyses from CALGB and NCI-C suggest that there may be a benefit to adjuvant
therapy for tumors ≥4 cm
Adapted from http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf.
Courtesy of Corey L. Langer, MD.
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Stage-Specific Hazard Ratios for Survival
Recent Adjuvant Trials
Trial
IB
II
IIIA
IALT1
0.95
0.93
0.79
JBR.102
0.94
0.59
N/A
ANITA3
1.10
0.71
0.69
CALGB4,5
0.8
N/A
N/A
JCOG (UFT)6
0.48
N/A
N/A
LACE7
0.93
0.83
0.83
Negative
Indeterminate
Positive
Not tested
1. Arriagada R, et al. N Engl J Med. 2004;350:351. 2. Winton T, et al. N Engl J Med. 2005;352:2589-2597
3. Douillard JY, et al. Lancet Oncol. 2006;7:719. 4. Strauss GM, et al. 42nd ASCO. June 2–6, 2006.
Abstract 7007. 5. Strauss GM, et al. 40th ASCO, June 5–8, 2004. Abstract 7019. 6. Kato H, et al. Proc Am
Soc Clin Oncol. 2003;22. Abstract 2498. 7. Pignon JP, et al. J Clin Oncol. 2006;24(suppl). Abstract 7008.
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Current Treatment Options for NSCLC (cont’d)
Stage III
(Locally
Advanced)
Treatment
Algorithm
for NSCLC
Neoadjuvant Chemotherapy
or Chemoradiation 
Surgery
(If Suitable)
Consolidative Chemotherapy
Chemotherapy +
Radiation Therapy
Palliative
Stage IV
(Metastatic)
Chemotherapy
+/- Targeted
Therapy
1st-Line
Gemcitabine + Platinum-based
Docetaxel + Platinum-based
Paclitaxel + Platinum-baseda
Vinorelbine
Vinorelbine + Platinum-based
2nd-Line
Docetaxelb
Pemetrexedc
Erlotinib
3rd-Line
Gefitinibd
Erlotinibe
aPaclitaxel/carboplatin
+ bevacizumab in selected patients. bAfter failure of prior platinum-based
chemotherapy. CAfter prior chemotherapy. dIndicated only for those who have already demonstrated a
therapeutic benefit on gefitinib. eAfter failure of both platinum-based and docetaxel chemotherapies.
Adapted from http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf
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Positive Trials of Chemoradiation for Locally
Advanced NSCLC

Induction:
Concurrent:
 Concurrent vs sequential:
 Consolidation:
 Targeted treatment:

4 (CALGB 84331; RTOG 88-08,2
French,3 UK4)
3 (EORTC5; Jeremic6,7)
3 (Furuse8; RTOG9; Czech10)
0 (SWOG 950411; HOG12; BTOG13)
0 (SWOG 002314; RTOG 023415)
1. Dillman RO, et al. J Natl Cancer Inst. 1996;88:1175. 2. Sause WT, et al. J Natl Cancer Inst. 1995;87:195.
3. Le Chevalier T, et al. J Natl Cancer Inst. 1991;83:417. 4. Cullen MH, et al. J Clin Oncol. 1999;17:3188.
5. Schaake-Koning C, et al. Lung Cancer. 1994;10(suppl 1):S263. 6. Jeremic B, et al. J Clin Oncol.
1996;14:1065. 7. Jeremic B, et al. J Clin Oncol. 1995;13:452. 8. Furose K, et al. J Clin Oncol. 1999;17:2692.
9. Glisson B, et al. J Clin Oncol. 2000;18:2990. 10. Zatloukal P, et al. Lung Cancer. 2004;46:87. 11. Gandara
DR, et al. J Clin Oncol. 2003;21:2004. 12. Hanna NH, et al. Abstract 7063. J Clin Oncol. 2006;24(June 20
suppl):18S. 13. Unpublished data. 14. Kelly K, et al. 41st ASCO. May 13–17. Abstract 7058. J Clin Oncol.
2005;23(June suppl):16S. 15. [please supply].
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Metastatic NSCLC Survival Advances
100
90
Best Supportive Care (BSC)
Percentage
80
Cisplatin
70
New Therapies
60
50
40
30
20
10
0
0
1
2
3
4
5
Survival (yr)
Courtesy of Corey L. Langer, MD.
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Randomized Trials with CT +/- Targeted Therapies
in Treatment-Naive NSCLC
THERAPY
Gefitinib1
Gefitinib2
Erlotinib3
Erlotinib4
AG33405
AG33406
BMS2752917
Lonafarnib8
Isis 35219
Bexarotene10
Bevacizumab11
TARGET
EGFR
EGFR
EGFR
EGFR
MMP
MMP
MMP
FT (ras)
PKC
RXR
VEGF
CT
GC
PC
PC
GC
PC
GC
PC
PC
PC
PC
PC
GROUP
AstraZeneca
AstraZeneca
Genentech/OSI
Genentech/OSI
Agouron
Agouron
BMSO
Schering
Isis
Ligand
ECOG
COMMENT
Closed, no benefit
Closed, no benefit
Closed, no benefit
Closed, no benefit
Closed, no benefit
Closed, no benefit
Closed, no benefit
Closed, no benefit
Closed, no benefit
Closed, no benefit
Closed, positive
EGFR = epidermal growth factor receptor; GC = gemcitabine + carboplatin; FT (ras) = farnesyl transferase (Ras protein); PKC = protein
kinase C-alpha; RXR = retinoid X receptor; CT = chemotherapy; GC = gemcitabine + carboplatin; PC = paclitaxel + carboplatin.
1. Giaconne G, et al. J Clin Oncol. 2004;22:777. 2. Herbst RS, et al. J Clin Oncol. 2004;22:785. 3. Herbst RS, et al. J Clin Oncol.
2005;23:5892. 4. Gatzemeier U, et al. Abstract 7010. J Clin Oncol. 2004;22(July suppl): 7010. 5. Smylie M, et al. Abstract 1226.
Proc Am Soc Clin Oncol. 2001;20:307a. 6. Bissett D, et al. J Clin Oncol. 2005;23:842. 7. Leighl NB, et al. J Clin Oncol. 2005;23:2831.
8. Schering-Plough press release. Available at: http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/02-052004/0002104279&EDATE=. Accessed April 17, 2007. 9. Lynch T, et al. J Clin Oncol. 10. Blumenschein GR, et al. Abstract 7001. J Clin
Oncol. 2005;23(June 1 suppl):16S. 11. Sandler A, et al. N Engl J Med. 2006;355:2542.
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