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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. Leading cause (29%) of cancer deaths More deaths from lung cancer than from prostate, breast, and colorectal cancers combined

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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
  • 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.

tnm staging of nsclc
TNM Staging of NSCLC

T = primary tumor; N = nodal involvement; M = distant metastasis.

Mountain CF. Chest. 1997;111:1710.

tnm staging of nsclc cont d
TNM Staging of NSCLC (cont’d)

T = primary tumor; N = nodal involvement; M = distant metastasis.

Mountain CF. Chest. 1997;111:1710.

lung cancer histology
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

5 year survival with lung cancer in the us
5-Year Survival with Lung Cancer in the US

Actual (%) Target (%)

Limited SCLC 15–25 25–30

Extensive SCLC <1 2–5

Stage IA NSCLC 70–85 85–95

Stage IB NSCLC 60–70 70–85

Stage IIA NSCLC 35–45 45–60

Stage IIB NSCLC 25–35 35–45

Stage IIIA NSCLC 5–20 20–30

Stage IIIB NSCLC 3–7 10–20

Stage IV NSCLC <1 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.

limited sclc combination chemotherapy and rt
Limited SCLCCombination 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) 5-Year Overall Survival (%)

JCOG1 Concurrent vs sequential EP/RT > EPRT 24 vs 18

NCI-C2 Early vs delayed concurrent CAV/EP/RTC2 >

CAV/EP/RTC6 20 vs 10

ECOG/RTOG3 BID vs QD concurrent EP/BID RT (45 Gy) >

EP/QD (45 Gy) RT 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.

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

SCLC Standard Therapy

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.

current treatment options for nsclc
Current Treatment Options for NSCLC

Stage I(LocalizedDisease)

Surgery

Adjuvant Treatmenta,b

TreatmentAlgorithmfor NSCLC

Stage II(LocalizedDisease)

Radiation Therapy(If Unsuitable for Surgery)

Adjuvant therapy for stage IB is controversial.

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.

stage specific hazard ratios for survival recent adjuvant trials
Stage-Specific Hazard Ratios for SurvivalRecent Adjuvant Trials

Positive

Negative

Not tested

Indeterminate

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.

current treatment options for nsclc cont d
Current Treatment Options for NSCLC (cont’d)

Neoadjuvant Chemotherapy

or Chemoradiation Surgery

(If Suitable)

Stage III(LocallyAdvanced)

Consolidative Chemotherapy

TreatmentAlgorithmfor NSCLC

Chemotherapy +

Radiation Therapy

Palliative

Stage IV(Metastatic)

Chemotherapy

+/- Targeted

Therapy

1st-LineGemcitabine + Platinum-basedDocetaxel + Platinum-based

Paclitaxel + Platinum-basedaVinorelbine

Vinorelbine + Platinum-based

2nd-Line

DocetaxelbPemetrexedc

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

positive trials of chemoradiation for locally advanced nsclc
Positive Trials of Chemoradiation for Locally Advanced NSCLC
  • Induction: 4 (CALGB 84331; RTOG 88-08,2 French,3 UK4)
  • Concurrent: 3 (EORTC5; Jeremic6,7)
  • Concurrent vs sequential: 3 (Furuse8; RTOG9; Czech10)
  • Consolidation: 0 (SWOG 950411; HOG12; BTOG13)
  • Targeted treatment: 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].

metastatic nsclc survival advances
Metastatic NSCLC Survival Advances

100

90

Best Supportive Care (BSC)

80

Cisplatin

70

New Therapies

60

Percentage

50

40

30

20

10

0

0

1

3

4

5

2

Survival (yr)

Courtesy of Corey L. Langer, MD.

randomized trials with ct targeted therapies in treatment naive nsclc
Randomized Trials with CT +/- Targeted Therapies in Treatment-Naive NSCLC

THERAPY TARGET CT GROUP COMMENT

Gefitinib1 EGFR GC AstraZeneca Closed, no benefit

Gefitinib2 EGFR PC AstraZeneca Closed, no benefit

Erlotinib3 EGFR PC Genentech/OSI Closed, no benefit

Erlotinib4 EGFR GC Genentech/OSI Closed, no benefit

AG33405 MMP PC Agouron Closed, no benefit

AG33406 MMP GC Agouron Closed, no benefit

BMS2752917 MMP PC BMSO Closed, no benefit

Lonafarnib8 FT (ras) PC Schering Closed, no benefit

Isis 35219 PKC PC Isis Closed, no benefit

Bexarotene10 RXR PC Ligand Closed, no benefit

Bevacizumab11 VEGF PC ECOG 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/02-05-2004/0002104279&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.