Non-Small Cell Lung Cancer Corey J. Langer, MD, FACP Medical Director, Thoracic Oncology Fox Chase Cancer Center Philadelphia, PA

Non-Small Cell Lung Cancer

Corey J. Langer, MD, FACP

Medical Director, Thoracic Oncology

Fox Chase Cancer Center

Philadelphia, PA

Case 2Early Stage NSCLC

• 53-year-old AA woman with 30 pack-year smoking history presents with vague DOE and cough after quitting smoking

• CXR demonstrates a 3 cm spiculated mass in the RML

• FNA shows a moderately differentiated adenocarcinoma with papillary and mucinous features

• IHC stains are positive for TTF-1

• CT and PET are otherwise entirely negative with no other sites of involvement

– The mediastinum appears normal


• She undergoes RMLobectomy and mediastinal node dissection

• Final pathology confirms a 3.2 x 3.0 cm RML adenocarcinoma with microscopic involvement in 3/5 peri-bronchial nodes, 2/5 hilar nodes and 2 of 6 subcarinal nodes.

– Remaining mediastinal nodes are negative


Is there a role for adjuvant therapy for this patient?

1. Yes

2. No


Is there a role for adjuvant therapy for this patient?

1. Yes

2. No

Answer: Yes, adjuvant therapy would be appropriate for this patient.


Which regimen has been shown in phase III studies to yield a survival advantage in this situation?

1. Cisplatin + paclitaxel

2. Cisplatin + docetaxel

3. Cisplatin + vinorelbine

4. Cisplatin + gemcitabine

5. Carboplatin + paclitaxel


Which regimen has been shown in phase III studies to yield a survival advantage in this situation?

1. Cisplatin + paclitaxel

2. Cisplatin + docetaxel

3. Cisplatin + vinorelbine

4. Cisplatin + gemcitabine

5. Carboplatin + paclitaxel

Answer: Cisplatin/vinorelbine has been shown to yield a survival

advantage in phase III studies.

Le Chevalier et al. Proc Am Soc Clin Oncol. 2003;22:2. Abstract and oral presentation. Arriagada et al. N Engl J Med. 2004;350:351.

*Each center selected chemotherapy regimen†Optional, but predefined by N stage at each center

Select eligibility criteria:

• Stage I-III

• Complete surgical resection within 60 days

• Age ≤ 75

(N = 1,867)

RANDOMIZE*

Cisplatin 80 mg/m2 q 3 wk 4 ORCisplatin 100 mg/m2 q 4 wk 3-4 ORCisplatin 120 mg/m2 q 4 wk 3

PLUS

Etoposide 100 mg/m2 3 days/cycle ORVinorelbine 30 mg/m2 weekly ORVinblastine 4 mg/m2 weekly OR Vindesine 3 mg/m2 weekly

(N = 935)

Observation ± Thoracic RT ≤ 60 Gy†

(N = 932)

Randomized International Adjuvant Lung Cancer Trial (IALT): Design

IALT: Overall Survival

Observation ± RT

Chemotherapy

Months

164286432602774935181308450624775932

At risk:

0

20

40

60

80

100

0 12 24 36 48 60

HR = 0.86 [0.76-0.98]P < 0.03O

vera

ll S

urvi

val (

%)

Median 5-yr OS (mos) OS (%)

Chemotherapy 50.8 44.5Observation ± RT 44.4 40.4

Le Chevalier et al. Proc Am Soc Clin Oncol. 2003;22:2. Abstract and oral presentation. Arriagada et al. N Engl J Med. 2004;350:351.

IALT Trial: Results

ARM Adjuvant chemo Control

Number of enrollees 935 932

Dead from disease progression 361 405

Tx-related deaths (N) 14 2

Compliance with RT (%) 71 85

Median DFS (mos.) 39.4 34.3

2-yr DFS (%) 61 55

5-yr DFS (%) 39 34

Median Survival Time (mos.) 50.8 44.4

2-yr OS (%) 70 67

5-yr OS (%) 44.5 40.4

Additional Perspectives from IALT

• Benefit seen across most demographic variables: gender, type of surgery, use of RT, geographical location

• Decreased Benefit

– PS 2; ≥ 65; Stage I/II; T1 vs. T2,3

• Stage-Specific LTS

Adjuvant Control Abs %↑

Stage I 65.6 64.9 0.7

Stage II 46.5 43.2 3.3

Stage III 37.4 29.9 7.5

Criticisms of IALT

• Heterogenous staging, chemo and application of RT (HR favored stage III, not stage I or II)

• Study actually closed earlier than planned because of emerging interest in neoadjuvant Tx

• Bio-correlatives still pending (could there have been molecular imbalances?)

• Elderly (> 75) excluded; how do we address this expanding cohort?

• Why was this trial positive when so many similar trials proved negative?

Other Recent Negative Trials of AdjuvantCT in Completely Resected NSCLC

Study CountryCT

Regimen# of

PatientsOutcome

on OS

INT 0115

ALPI/EORTC

BLT

USA

Italy/Europe

International

VP16-P x 4

MVP x 3

V-P x 4

462

1197

481

Negative

Negative

Negative

Recently Completed Positive Randomized Adjuvant Trials in Early Stage NSCLC

Stage No. Intervention

CALGB 9633 IB 500 Carboplatin/paclitaxel

NCI-C IB-II 480 Cisplatin/vinorelbine

ANITA I-IIIA 840 Cisplatin/vinorelbine

IALT I-IIIA 1,870 Cisplatin/vincalkaloids or

Cisplatin/etoposide

2004-2006: Paradigm Shift

BR 10: NCI-Canada Trial of Adjuvant Vinorelbine and Cisplatin in Resected NSCLC

Schema

Resected stage IB and II NSCLC

Stratified by:• Nodal status• RAS mutation status

(N = 482)

Arm A q 4w 4 cycles

Cisplatin 50 mg/m2 days 1, 8

Vinorelbine 25 mg/m2 day 1, 8, 15, 21

Arm BObservation

RANDOMIZE

• Started July 1994• Completed April 2001

Winton et al. NEJM. 2005;352:2589-2597.

BR 10: NCI-Canada Trial of Adjuvant Vinorelbine and Cisplatin in Resected NSCLC

Survival

0 24 48 72 96

Months

0

20

40

60

80

100

Vinorelbine/cisplatin

Observation

HR = 0.7; P = 0.012

% S

urvi

val

5-year survival: 69% vs. 54%

Winton et al. NEJM. 2005;352:2589-2597.

Strauss et al. Proc Am Soc Clin Oncol. 2004;22(No 14S):621s Abstract 7019

Paclitaxel and Carboplatin Following Resection in Stage IB NSCLC

CALGB 9633

T2 N0 M0

Stage IB

NSCLC

Paclitaxel 200 mg/m2

+

Carboplatin AUC 6

q 3w x 4 cycles N = 173

ObservationN = 171

Randomized within 4-8 weeks of resection

Stratified by:• Squamous vs. adenocarcinoma

• Poorly differentiated vs. other

• Mediastinoscopy: yes or no

Complete Surgical

Resection

• Started July 1994• Completed April 2001

Paclitaxel and Carboplatin Following Resection in Stage IB NSCLC

CALGB 9633

0 20 40 60 80

0

20

40

60

80

100

Months

% S

urvi

val

Paclitaxel/carboplatin

Observation

HR = 0.62; P = 0.028

4-year survival: 71% vs. 59%

Strauss et al. Proc Am Soc Clin Oncol. 2004;22(No 14S):621s Abstract 7019

Adjuvant Navelbine International Trialist Association (ANITA Study)

Open, Multicentric (101 centers), Phase III Study(840 patients enrolled)

Douillard J-Y et al. Lancet Oncol 7:719, 2006

Surgery

Observation

Chemotherapy (Vinorelbine/CDDP)*

*Vinorelbine (30 mg/m2) q wk x 16 + Cisplatin 100 mg/m2 q 4 wks x 4

Months

Sur

viva

l Dis

trib

utio

n F

unct

ion

1.00

0.75

0.50

0.25

00 20 40 60 80 100 120

OBS. NVB + CDDP

Median (mos.) 43.8 65.8

P-value 0.013

Hazard Ratio 0.79 [0.66 - 0.95]

ObsNVB + CDDP

ANITA Trial Overall Survival (ITT Population)


ANITA Trial Results

Arm Observation Adjuvant

No 433 407

RFS (mo) 21 36

Median Surv (mos.)* 44 66

2-yr OS 63 68

5-yr OS 43 51

7-yr OS 37 48

5-yr OS by Stage

Stage I 62 63

Stage II 39 52

Stage III 26 42

* P = 0.002; HR 0.79 (0.66-0.95)


ANITA Trial Adjuvant Toxicities

Neutropenia Gr 3+4 86%

Febrile Neutropenia 12.5%

Nausea/Vomiting Gr 3+4 27%

Aesthenia 28%

Constipation 5%

Peripheral Neuropathy 3%

Drug-Related Fatality 1%


Scorecard for Adjuvant CTSubset Analyses as of 2005

Stage IA IB II IIIA

ALPI

IALT

NCI-C

CALGB

ANITA

Not tested Positive Negative

Positive Adjuvant Trials: NSCLC

Trial Stage Control Adj P-value Rel Surv

IALT I-III 40.5% 44.5% < 0.03 10%

BR10 IB-II 54% 69% 0.012 28%

CALGB IB 59% 71% 0.028 20%

ANITA I-III 43% 51% 0.013 19%

ASCO: 2006

0 2 4 6 8

Survival Time (Years)

0.0

0.2

0.4

0.6

0.8

1.0

Pro

babi

lity

ObservationChemo

0 1 2 3 4 5 6 7 8 9

HR = 0.80; 90% CI: 0.60-1.07 P = 0.10

ASCO: 2004

0 2 4 6 8


0.0

0.2

0.4

0.6

0.8

1.0

Pro

babi

lity

0 1 2 3 4 5 6 7 8 9

HR = 0.62; 90% CI: 0.44-0.89 P = 0.028

ObservationChemo

CALGB 9633: Overall Survival Then and Now

CALGB 9633 (ASCO 2006)

Arm CbP Obs P-value

MS 95m 78m 0.10

DFS 89m 52m 0.03

Recurred or Dead 43% 52%

5-yr DFS 52% 48% 0.21

3-yr OS* 79% 70%

5-yr OS^ 59% 57% 0.375

• Median F/U still short: < 5 yrs; • 150 deaths required for final analysis; yet only 131 have died• ^5-yr OS still significantly better for tumors ≥ 4 cm (HR = 0.62; P = 0.04)

Strauss et al. Proc Am Soc Clin Oncol. 2006; Abstract 7007.

CALGB 9633 Survival: Patients with Tumors ≥ 4.0 cm

0 2 4 6 8


0.0

0.2

0.4

0.6

0.8

1.0

Pro

ba

bilit

y

ObservationChemo

0 1 2 3 4 5 6 7 8 90 1 2 3 4 5 6 7 8 9

HR = 0.66; 90% CI: 0.45-0.97

P = 0.04

N = 97

N = 99

NSCLC 2006Positive Adjuvant Trials

Trial Stage Control Adj P-value Rel Surv

IALT I-III 40.5% 44.5% <0.03 10%

BR10 IB-II 54% 69% 0.012 28%

CALGB IB 57% 60% 0.10 5%

ANITA I-III 43% 51% 0.013 19%

Scorecard for Adjuvant CTSubset Analyses: Updated (ASCO 2006)

Stage IA IB II IIIA

ALPI

IALT

NCI-C

CALGB

ANITA

Not tested Positive

Negative Indeterminate

Stage-Specific Hazard RatiosRecent Adjuvant Trials

Trial IB II IIIA

IALT 0.95 0.93 0.79

BR-10 0.94 0.59 N/A

ANITA 1.10 0.71 0.69

CALGB 0.80 N/A N/A

JCOG (UFT) 0.48 N/A N/A

LACE 0.92 0.83 0.83

Negative Positive

Indeterminate Not tested

ECOG 1505: Adjuvant Bevacizumab

Investigator Choice of 3 chemo regimens^ Allows ≥ 4cm

RANDOM IZE

Chemotherapyx 4 cycles

Elibility:• Resected IB^ -IIIA• Lobectomy• No prior chemo• No planned XRT• No h/o CVA/TIA• No ATE w/in 1-yr

Stratified:• Stage• Histology• Gender• Chemotherapy

regimen

Chemotherapyx 4 cycles

+Bevacizumab

x 1-year

Chemotherapy Regimens

• Therapy to start 6-12 weeks post-operatively– Investigator Choice of Chemo x 4 cycles (12 wks)

• Carboplatin/Paclitaxel– Carboplatin AUC 6, Paclitaxel 200 mg/m2 both d 1 q21 d

• Cisplatin/Vinorelbine– Cisplatin 75 mg/m2 d 1, Vinorelbine 25 mg/m2 d1,8 q21 d

• Cisplatin/Docetaxel– Cisplatin 75 mg/m2 d 1, Docetaxel 75 mg/m2 d 1 q21 d

• Cisplatin/Gemcitabine– Cisplatin 75 mg/m2 d 1, Gemcitabine 1,250 mg/m2 d1,8 q 21 d

• Bevacizumab 15 mg/kg q 21 days x 12 months

Chemotherapy Regimens

• Therapy to start 6-12 weeks post-operatively– Investigator Choice of Chemo x 4 cycles (12 wks)

• Carboplatin/Paclitaxel– Carboplatin AUC 6, Paclitaxel 200 mg/m2 both d 1 q21 d

• Cisplatin/Vinorelbine– Cisplatin 75 mg/m2 d 1, Vinorelbine 25 mg/m2 d1,8 q21 d

• Cisplatin/Docetaxel– Cisplatin 75 mg/m2 d 1, Docetaxel 75 mg/m2 d 1 q21 d

• Cisplatin/Gemcitabine– Cisplatin 75 mg/m2 d 1, Gemcitabine 1,250 mg/m2 d1,8 q 21 d

• Bevacizumab 15 mg/kg q 21 days x 12 months


Which marker has been shown to be predictive of benefit in this situation?

1. EGFR

2. RAS

3. TTF-1

4. ERCC-1

5. HER-2


Which marker has been shown to be predictive of benefit in this situation?

1. EGFR

2. RAS

3. TTF-1

4. ERCC-1

5. HER-2

Answer: ERCC-1 has been shown to be predictive of benefit.

Immunohistochemical Staining of the Excision Repair Cross-Complementing 1 (ERCC-1) Protein as Predictor for Benefit of Adjuvant

Chemotherapy (CT) in the International Lung Cancer Trial (IALT)

Soria et al., ASCO 2006 Abstract 7010

IALT Trial

• 761 pts. (28 centers,14 countries) evaluable for ERCC-1 expression

• ERCC-1 repairs cisplatin-DNA adducts, so expression indicates platinum resistance

• ERCC-1 a “double-edged sword”; worse prognosis of NSCLC if low expression, but more responsive to platinum

ERCC-1-Negative TumorsOverall Survival

224 194 161 121 81 47202 163 120 91 59 35

0%

20%

40%

60%

80%

100%

0 1 2 3 4 5YearsNo at risk

Chemotherapy

Control

Control

Chemotherapy

Ove

rall

Sur

viva

l

Adjusted HR = 0.65, 95% PI [0.50-0.86] P = 0.002

Soria et al. Proc Am Soc Clin Oncol. 2006; Abstract 7010.

ERCC-1-Positive TumorsOverall Survival

346285121147165336996127149170

0%

20%

40%

60%

80%

100%

0 1 2 3 4 5Years

No at risk

Chemotherapy

Control

Ove

rall

Sur

viva

l

Control

Chemotherapy

Adjusted HR = 1.14, 95% CI [0.84-1.55]P = 0.40


Results of ERCC-1 Analysis5-Year Survival

• Overall positivity = 44% (H-score > 1.0)

• Significant correlation of ERCC-1 expression seen with age (lower in younger pts.), histological subtype (lower in adenocarcinoma), and pleural invasion (lower if no pleural invasion)

Chemo

(N = 389)

Control

(N = 372)

HR

P-value

ERCC-1 negative

(N = 426)47%

56 mos.

39%

42 mos.

0.65

.002

ERCC-1 positive

(N = 335)

40%

50 mos.

46%

55 mos.

1.14

.40

Predictive Adjusted Analysis (5-year survival)



Is there a role for adjuvant XRT in patients with N2 involvement?

1. Yes

2. No

3. Controversial


Is there a role for adjuvant XRT in patients with N2 involvement?

1. Yes

2. No

3. Controversial

Answer: The use of adjuvant XRT in patients with N2 involvement is

controversial.

Adjuvant Radiotherapy

Local recurrence went from 41% to 3% with RTx

Weisenburger et al, NEJM 1986.

LCSG 773

T2N1, T3, chest wall, N2completely resected (R0)

squamous cell carcinoma only

ObservationN = 108

Adjuvant RTx 50 Gy/6 wks

N = 102

Adjuvant Radiotherapy

N2 appeared to gain 1 month in survival...

Stephens et al, Br J Cancer 1996.

MRC Lung Cancer Working Party

T1-2 N1-2 NSCLCcompletely resected (R0)

N = 306

ObservationAdjuvant RTx

40 Gy/15 fractions

Adjuvant RadiotherapyMeta-Analysis 1998

• Individual data from 9 randomized trials including 2,128 patients

• Treatment details (staging, surgery, RT) highly variable among series

• PORT: better local control: 29% fewer local recurrences - 195 LR vs. 276 LR for no RT

• Overall HR = 1.21 (1.08-1.34) ~ survival decrement of 7% at two years (55% vs. 48%)

• Increase risk greater for early stage patients (Stage I/II vs. III)

Lancet 25 July 1998.

PORT Meta-AnalysisSurvival Curves

Stewart et al, Lancet 1998.

PORT Heterogeneity of Hazard

• No increased risk for patients with N2 disease

• Patients with the least to gain have the most to lose

Stewart et al, Lancet 1998.

PORT Meta-AnalysisMethodologic Flaws

• Variable and unspecified staging• Variable and unspecified interval between resection and

PORT• Inadequate RT

– Suboptimal doses– Poor treatment planning– Outmoded techniques (e.g: use of low-energy photons or 60Co

for a substantial proportion of patients)

• Inclusion of N0 patients

• Unpublished data (2 of 9 studies)• Relatively short F/U (< 4 yrs)

Risks of PORT with Modern Technology

• Retrospective review

– 202 patients treated with surgery and PORT for Stage II and III disease

– Median dose 55 Gy

– Actuarial rate of death from intercurrent disease was 13.5% compared to expected rate of 10%

Machtay et al JCO 2001.

OBS

NVB + CDDP

PORT OBS(N = 144)

NVB + CDDP(N = 88)

Median (mos.) 33.3 47.4

5-Yr survival (%) 33 44.6

5-Yr overall survival 43 51

Overall Survival in Patients Receiving PORTANITA Trial


Median Overall Survival:

65.7 mos. CT

31.2 mos. OBS

46.6 mos.

93.6 mos.

50.2 mos.

25.9 mos.

CT + PORT

CT

PORT

OBS

Duration of Survival (Months)

0 20 40 60 80 100 120

0.00

0.25

0.50

0.75

1.00

Su

rviv

al

Dis

trib

uti

on

Fu

nc

tio

nOverall Survival in N1 Patients

ANITA Trial


0.00

0.25

0.50

0.75

1.00

0 20 40 60 80 100 120

Su

rviv

al

Dis

trib

uti

on

Fu

nc

tio

n


32.6 mos. CT

20 mos. OBS

47.4 mos.

23.8 mos.

22.7 mos.

12.7 mos.

CT + PORT

CT

PORT

OBS

Overall Survival in N2 PatientsANITA Trial



0.00

0.25

0.50

0.75

1.00

0 20 40 60 80 100 120

Su

rviv

al

Dis

trib

uti

on

Fu

nc

tio

n


32.6 mos. CT

20 mos. OBS

47.4 mos.

23.8 mos.

22.7 mos.

12.7 mos.

CT + PORT

CT

PORT

OBS

Overall Survival in N2 PatientsANITA Trial


RT Effect? Or Serendipity?


ANITA5-Year Survival According to Treatment

N0 N1 N2

Observation 62.3% 31.4% 16.6%

PORT 43.8% 42.6% 21.3%

Chemotherapy 59.7% 56.3% 34.0%

Chemotherapy + PORT

44.4% 40.0% 47.4%


PORT Stage II-III SEER Data

• 7,465 pts, lobectomy or pneumonectomy (1988-2002)• > 4 mos. survival post-op• Median F/U: 3.5-years

Lally et al., JCO 2006.

Conclusions

• No role for PORT in N0 (N1?) patients

• Role of PORT in N2 patients remains controversial

• Modern RT techniques essential

• Recent randomized trials with chemo do not show increased toxicity with RT

• Randomized trials are necessary

“Lung ART”P.I. Dr. Cécile Le Pechoux

Sponsors: FNCLCC, IFCT, LARS-G, EORTC

• Completely resected N2 NSCLC

• Primary end-point: DFS

• Sample size: 700 pts

SURGERY

Conformal RT54 Gy/27-30 fxs

No post-op RT

• Pre- or post-op chemotherapy allowed• Concomitant chemo not allowed

Case 3Advanced NSCLC

• 49-year-old WM with 25 pack-year smoking history presents with 5 lb weight loss, rib pain and dyspnea

• PE shows a 2 cm (L) mid-cervical node with decreased breath sounds at the (L) base

• CXR demonstrates a (L) pleural effusion, with a mass abutting the lateral chest wall

• CT of the neck, chest and abdomen reveals a 3.8 cm spiculated mass invading the chest wall in the (L) mid-lung, a moderate (L) pleural effusion, mediastinal and (L) hilar adenopathy, and (L) mid-cervical and supraclavicular nodes. The (R) adrenal appears nodular and enlarged (~3 cm). The liver appears normal.

• Pleural tap confirms adenocarcinoma, as does FNA of the (L) mid-cervical node

• MRI of the brain is negative


Phase III data suggest a benefit for which of the following regimens?

1. Carboplatin + paclitaxel + bevacizumab

2. Carboplatin + paclitaxel + erlotinib

3. Cisplatin + gemcitabine + bevacizumab

4. Cisplatin + gemcitabine + erlotinib

5. 1 and 3


Phase III data suggest a benefit for which of the following regimens?

1. Carboplatin + paclitaxel + bevacizumab

2. Carboplatin + paclitaxel + erlotinib

3. Cisplatin + gemcitabine + bevacizumab

4. Cisplatin + gemcitabine + erlotinib

5. 1 and 3

Answer: Phase III data suggest a benefit for regimens 1 and 3.


• The patient receives 6-cycles of gemcitabine + carboplatin + bevacizumab

• He gains weight, with complete resolution of rib pain and dyspnea and enters a PR radiographically


What is indicated at this point?

1. Maintenance bevacizumab

2. Maintenance erlotinib + bevacizumab

3. Maintenance docetaxel

4. Observation (active surveillance)


What is indicated at this point?

1. Maintenance bevacizumab

2. Maintenance erlotinib + bevacizumab

3. Maintenance docetaxel

4. Observation (active surveillance)

Recommended Approach: At this point, maintenance bevacizumab should be considered

for this patient.

Cisplatin-Based Therapyin Advanced NSCLC

• Improves survival

– Median: 2 mos.

– 1-yr: 10% survival increase

– Hazard rate reduction of 26%

• Relieves symptoms: 66%-78% in Stage III/IV

• Improves QoL

• Cost-effective

NSCLC: Standard Agents

OLD (pre-1990) NEWER (post-1990)• Cisplatin • Paclitaxel• Etoposide • Docetaxel• Vinblastine • Gemcitabine• Ifosfamide • Vinorelbine• Mitomycin-C • Irinotecan • Carboplatin

LATEST (post-2000)• Pemetrexed• Gefitinib• Erlotinib• Bevacizumab

Metastatic NSCLC Survival Advances

Are We Making Progress in NSCLC?

• Modest, but real increase in survival

• Potential explanations

– New agents

Are We Making Progress in NSCLC?

• Modest, but real increase in survival

• Potential explanations

– New agents

– Stage migration

– Selection bias

– Second-line Tx

– Improved BSC

Current Treatment Options for NSCLCNCCN Guidelines

• Chemotherapy and targeted therapy (inoperable or unresectable, locally advanced or metastatic disease)

– First-line

• Gemcitabine plus platinum-based chemotherapy

• Taxanes (docetaxel or paclitaxel) plus platinum-based chemotherapy

• Vinorelbine, single-agent or in combination with platinum-based chemotherapy

• Addition of bevacizumab in selected pts

– Second-line

• Docetaxel (after failure of prior platinum-based chemotherapy)

• Pemetrexed (after prior chemotherapy)

• Erlotinib (approved 11/04)

– Third-line

• Erlotinib or gefitinib* (after failure of both platinum-based and docetaxel chemotherapies)

*now only approved for those who have already demonstrated a benefit to gefitinib

Pfister et al. J Clin Oncol. 2004;22:330.Ginsberg et al. Non–small cell lung cancer. In: Cancer: Principles & Practice of Oncology. 2001:925.

2003 ASCO Guidelines for Stage IV NSCLC

• 2-drug combination regimen recommended as first-line chemotherapy

– Non-platinum-based chemotherapy potential alternative in first-line therapy

– Consider single-agent therapy for elderly or patients with PS 2

• 3 agents: no advantage over 2

• 4 to 6 cycles of chemo for non-progressors

• No proven role for maintenance or consolidation with cytotoxics

ECOG 1594Treatment Schema

Schiller JH et al. N Engl J Med. 2002;346:92-98.

Arm A* q 3 wkStage IIIB or IV

NSCLC Stratified by:• Extent of disease • PS• Weight loss• Brain metastases

(N = 1,207)

Cisplatin: 100 mg/m2, day 1Gemcitabine: 1,000 mg/m2, days 1,8,15 (N = 301)

Docetaxel: 75 mg/m2, day 1Cisplatin: 75 mg/m2, day 1 (N = 304)

Arm C q 3 wk

Paclitaxel: 225 mg/m2, day 1Carboplatin: AUC=6, day 1 (N = 299)

Arm D q 3 wk

Arm B q 4 wk

Paclitaxel: 135 mg/m2, day 1Cisplatin: 75 mg/m2, day 2 (N = 303)

RANDOM

I

ZE

*Control arm

ECOG 1594Survival

NS = not significant.

% S

urvi

val

Months

Cisplatin + paclitaxel 7.8; P = NSCisplatin + gemcitabine 8.1; P = NSCisplatin + docetaxel 7.4; P = NSCarboplatin + paclitaxel 8.1; P = NS

Median survival (mo)100

80

60

40

20

0

0 5 10 15 20 25 30


ORR = overall response rate; TTP = time to tumor progression.

ECOG 1594Efficacy

Paclitaxel-Cisplatin(N = 288)

Gemcitabine-Cisplatin(N = 288)

Docetaxel-Cisplatin(N = 289)

Paclitaxel-Carboplatin

(N = 290)

ORR (%) 21 22 17 16

TTP (mos.) 3.4 4.2 3.7 3.1

Median survival (mos.)

7.8 8.1 7.4 8.1

1-year survival (%) 31 36 31 34

2-year survival (%) 10 13 11 11


E4599: Phase III Trial of Bevacizumab/Paclitaxel/Carboplatin

in First-Line Advanced NSCLC

Stratified by

• Disease stage

• Degree of weight loss

• Prior radiotherapy

• Measurable disease

Bevacizumab 15 mg/kg q 3wk until

progression of disease or

unacceptable toxicity

First-line treatment of

patients with stage IIIB with malignant

pleural effusion,or IV, or recurrent

NSCLC(N = 878)

Bevacizumab (BV)15 mg/kg q 3wk

+ PC × 6 (BV/PC)

Paclitaxel 200 mg/m2

carboplatin AUC 6 (PC) q 3wk × 6

(no crossover permitted)

Progression of disease or

unacceptable toxicity

End points• Primary

– Overall survival

• Secondary

– Response rates

– Progression-free survival

– Toxicity

Avastin® (bevacizumab) prescribing information. South San Francisco, Calif: Genentech; 2006.

E4599: Patient Characteristics

Patients, %

(N = 878)

Stage IIIB disease 12

Previous weight loss ≥ 5% 28

Age ≥ 65 years 43

Male sex 55

Sandler et al. NEJM 2006.

E4599: Overall Survival

HR = 0.80; P = .013

BV/PC 51.0% 22.0% 12.3 mos.

PC 44.4% 15.4% 10.3 mos.

0.0

0.2

0.4

0.6

0.8

1.0

Pro

port

ion

surv

ivin

g

0 6 42 4818 30

12 mos. 24 mos. Median

12 24 36

444 318 1 0104 9190 36 5

434 340 3 0127 25216 54 8

PC

BV/PC

MonthsPatients at risk

Median 12.3 mos.

Median 10.3 mos.


E4599: Investigator Assessed* Progression-Free Survival

Genentech, data on file.

HR: 0.65, P < .0001

BV/PC 56.0% 21.0% 6.4 mos.

PC 39.0% 9.0% 4.8 mos.

0.0

0.2

0.4

0.6

0.8

1.0

Pro

port

ion

with

PF

S

0 6 42 4818 30

6 mos. 12 mos. Median

12 24 36

444 126 0 013 127 2 0

434 201 0 021 370 6 1

PC

BV/PC

MonthsPatients at risk

Median 6.4 mos.

Median 4.8 mos.

*Based on investigator assessment which was not independently verified.

E4599: Outcome*

Arm CbP CbPB

RR (%) 15 35

PFS (mos.) 4.8 6.4

MS (mos.) 10.2 12.5

1-yr OS (%) 43.7 51.9

2-yr OS (%) 16.9 22.1

* All Differences were statistically significant P < 0.05


Randomized Trials with CT ± Targeted Therapies in Treatment-Naïve NSCLC

TRIAL TARGET CT GROUP COMMENT

ZD1839 EGFR GC AstraZeneca Closed, no benefit

ZD1839 EGFR PC AstraZeneca Closed, no benefit

OSI 774 EGFR PC Genentech/OSI Closed, no benefit

OSI 774 EGFR GC Genentech/OSI Closed, no benefit

AG3340 MMP PC Agouron Closed, no benefit

AG3340 MMP GC Agouron Closed, no benefit

BMS275291 MMP PC BMSO Closed, no benefit

Lonafarnib FT (ras) PC Schering Closed, no benefit

ISIS 3521 PKC PC ISIS Closed, no benefit

Targretin RXR PC Ligand Closed, no benefit

E4599 VEGF PC ECOG Closed, positive

E4599: Key Entry Criteria

• Key inclusion criteria– First-line locally advanced, metastatic, or recurrent NSCLC

– ECOG PS 0 or 1

– Measurable or non-measurable disease

• Key exclusion criteria*– Patients with predominant squamous histology

– Central nervous system metastases

– Gross hemoptysis (≥ 0.5 tsp of red blood) added with Protocol Amendment 1

– Unstable angina

– Patients receiving therapeutic anticoagulation*Patients were not excluded from study E4599 due to tumor location or unclassified histology (not otherwise specified, NOS).


Phase III Study of Bevacizumab + Cisplatin + Gemcitabine in Chemo-Naïve Patients with Advanced or Recurrent NSCLC (B017704)

PDPD

PDPD

PDPD

Bevacizumab

Bevacizumab

2

2

1

1

Placebo 7.5 + CGPlacebo 7.5 + CG

Bevacizumab15mg/kg + CGBevacizumab15mg/kg + CG

Bevacizumab7.5mg/kg + CGBevacizumab

7.5mg/kg + CG

Placebo 15 + CGPlacebo 15 + CG

• Previously untreated,• IIIb, IV or recurrent• non-squamous

NSCLC• No tumor invasion of

major blood vessels• No ≥ Gr 2 hemoptysis• No brain mets

• Previously untreated,• IIIb, IV or recurrent• non-squamous

NSCLC• No tumor invasion of

major blood vessels• No ≥ Gr 2 hemoptysis• No brain mets

RANDOMIZE

RANDOMIZE

• Primary Objective: PFS

• Statistical Analysis: median PFS 4.5 months placebo versus 6.4 months bevacizumab (corresponding to a hazard ratio of 0.7)

Manegold et al. Proc Am Soc Clin Oncol. 2007; Abstract LBA7514.

Phase III: Bevacizumab/Cisplatin/Gemcitabine PFS: Primary Analysis

Arm CGPCGBv

(7.5 mg/kg)

CGBv

(15 mg/kg)

No. Patients 347 345 351

Med. PFS (mos.) 6.1 6.7 6.5

HR -- 0.75 0.82

95% CI -- 0.62, 0.91 0.68, 0.98

P-value -- 0.0026 0.0301


Phase III: Bevacizumab/Cisplatin/Gemcitabine PFS: Primary Analysis (ITT)

No. at risk

Placebo + CG 347 228 122 36 12 3 0

Bv 7.5 + CG 345 251 150 52 18 3 0

Bv 15 + CG 351 238 148 46 16 5 0

1.0

Pos

sibi

lity

of P

FS

0.8

0.6

0.4

0.2

0.0

1.0

Time (months)

0.8

0.6

0.4

0.2

0.0

0 6 12 183 9 15

Bv 7.5mg/kg + CG

Placebo +CG

Bv 15mg/kg + CG

Placebo

CG

(N = 347)

Bv 7.5 mg/kg

CG

(N = 345)

Bv 15 mg/kg

CG

(N = 351)

Median PFS (mos) 6.1 6.7 6.5

HR

[95% CI]

- - - 0.75

[0.62, 0.91]

0.82

[0.68, 0.98]

P-value - - - 0.0026 0.0301


Phase III: Bevacizumab/Cisplatin/Gemcitabine PFS: Primary Analysis (NPT Censored*)

Arm CGPCGBv

(7.5 mg/kg)

CGBv

(15 mg/kg)


Med. PFS (mos.) 6.1 6.7 6.6

HR -- 0.68 0.74

95% CI -- 0.56 ,0.83 0.60, 0.90

P-value -- 0.0001 0.0021

*7% of pateints receive non-protocol antineoplastic therapy (NPT) prior to disease progression


Phase III: Bevacizumab/Cisplatin/Gemcitabine Overall Response

Arm CGPCGBv

(7.5 mg/kg)

CGBv

(15 mg/kg)


OR (%) 20 34 30

P-value -- < 0.0001 0.0017

Dur. of Resp. (mos.) 4.7 6.1 6.1


Phase III: Bevacizumab/Cisplatin/Gemcitabine Conclusions

• Statistically significant progression-free survival advantage for either low- or high-dose bevacizumab in combination with GC compared to GC alone

• Significant increase in response rate

• Survival data immature

• No new safety signals; no untoward toxicity


Erlotinib: First-Line Lung Cancer TRIBUTE

• Primary Endpoint: Survival• Secondary Endpoints: Symptomatic progression/QOL, response rate

NSCLC • IIIB/IV• PS 0/1• No prior chemotherapy

Stratification:• IIIB vs IV• Weight loss• Measurable vs. evaluable

RANDOMIZE

Carbo/Paclitaxel x 6+ Placebo

Carbo/Paclitaxel x 6+ Erlotinib

*Genentech Sponsored (US)

Erlotinib: First-Line Lung Cancer TRIBUTE




RANDOMIZE

Carbo/Paclitaxel x 6+ Placebo

Carbo/Paclitaxel x 6+ Erlotinib

NEGATIVE

*Genentech Sponsored (US)

Erlotinib: First-Line Lung Cancer TALENT

*Roche Sponsored (EU)




RANDOMIZE

Gemcitabine/Cisplatin x 6+ Placebo

Gemcitabine/Cisplatin x 6+ Erlotinib

Erlotinib: First-Line Lung Cancer TALENT

*Roche Sponsored (EU)




RANDOMIZE

Gemcitabine/Cisplatin x 6+ Placebo

Gemcitabine/Cisplatin x 6+ Erlotinib

NEGATIVE

TRIBUTE & TALENT Trials

Arm CPE CP

No. Pts. 526 533

OR (%) 21.5 19.3

TTP (mos.) 5.1 4.9

MS (mos.) 10.8 10.6

Arm GPE GP

No. Pts. 586 586

TTP (mos.) 5.4 5.6

MS (mos.) 9.9 10.1

1-yr OS (%) 41 42

Gatezemeier et al. Proc Am Soc Clin Oncol. 2004; Abstract 7010.Herbst et al. Proc Am Soc Clin Oncol. 2004; Abstract 7011.

Maintenance or Consolidation Therapy

Is There a Role?

Immediate vs. Delayed Second-Line Docetaxel in Advanced NSCLC

Eligibility• NSCLC Stage IIIB/IV • Chemo-naïve• ECOG PS 0-2• CNS Mets allowed

GC Phase

Gemcitabine, 1000 mg/m2,

d1, 8 Carboplatin AUC 5, d1

q 21 days x 4

RANDOMIZE

Immediate Docetaxel

75mg/m2 d1 q 21 days until PD or

maximum of 6 cycles

Delayed Docetaxel

BSC → start therapy at PD75mg/m2 on d1 q 21 days,

until PD or maximum of 6 cycles

CR, PRSD

• Primary endpoint: – Overall survival – HR = 1.43

Fidias et al. Proc Am Soc Clin Oncol. 2007; Abstract LBA7516.

Immediate vs. Delayed DocetaxelPatient Disposition

Chemo-naϊveStage IIIB/IV

NSCLC

N = 562

GC PhaseN = 552

(388 received 4 cycles)

Off Study

N = 245

RandomizedSD, PR,

CRN = 307

ImmediateN = 153

Delayed

N = 154

ImmediateTreatedN = 142

DelayedTreatedN = 91

Treated

ORR 29%


Patients at Risk

I: 153 72 27 11 5D 154 28 10 4 2

Please note: the PFS curves only showed up to 24 months since very few patients left without PD/survival 24 months after randomization.

therapy Delayed Immediated

Pro

po

rtio

n S

urv

ivin

g

0.0

0.2

0.4

0.6

0.8

1.0

Progression Free Survival (months)0 3 6 9 12 15 18 21 24

Immediate vs. Delayed DocetaxelPFS: Total Randomized Population

Immediate (N = 153)

Delayed (N = 154)

LRP-Value

Median PFS (mos.) (95% CI)

6.5(4.4, 7.2)

2.8(2.6, 3.4)

< 0.0001

12-month PFS(95% CI)

20%(13, 26)

9%(5, 14)


Overall Survival Time (months)

Sur

viva

l Pro

babi

lity

I: 153 111 56 27 12 5 2D: 154 98 45 22 9 3 2

Immediate vs. Delayed DocetaxelOverall Survival: Total Randomized Population

Immediate (N = 153)

Delayed (N = 154)

LRP-Value

Median OS, (mos.) (95% CI)

11.9(10.0, 13.7)

9.1(8.0, 11.2)

0.071

12-mo survival (95% CI)

48.5%(39.9, 57.1)

38.3% (30.0, 46.5)

Patients at Risk


Immediate vs. Delayed DocetaxelConclusions

• Significant improvement in PFS

• Trend toward improved OS (underpowered)

• Thought-provoking, hypothesis-generating, but….

Not yet ready for prime time


• Patient receives bevacizumab alone for 10 months with excellent quality of life

• Unfortunately, 15 months after diagnosis, he develops H/A and subtle (R) arm weakness

• MRI of the brain demonstrates multiple space-occupying lesions with vasogenic edema

• CT confirms new pulmonary nodules and regrowth of the (R) adrenal lesion

• He receives WBRT with complete resolution of his neurologic symptoms

• He is offered salvage therapy


Which would be an inappropriate salvage therapy?

1. Docetaxel

2. Erlotinib

3. Pemetrexed

4. Double-dose pemetrexed


Which would be an inappropriate salvage therapy?

1. Docetaxel

2. Erlotinib

3. Pemetrexed

4. Double-dose pemetrexed

Correct answer: Double-dose pemetrexed would be inappropriate salvage

therapy.

Approved Second-Line Therapies for Advanced and Metastatic Disease

Clinical Efficacy

TAX 317B: Second-Line NSCLCSchema

Shepherd et al. J Clin Oncol. 2000;18:2095.

Stage IIIB or IV NSCLC Stratified by:

• PS• Best response

to cisplatin

N = 204

Arm ADocetaxelN = 104

Arm B q 3wControl

Best supportive careN = 100

RANDOMIZE

RANDOMIZE

Docetaxel 75 mg/m2 q 3w

N = 55

Docetaxel 100 mg/m2 q 3w

N = 49

Premed: Dexamethasone 8 mg PO bid 5 days (first dose 24 hr prior to each docetaxel infusion) for the docetaxel groups.

TAX 317B: Second-Line NSCLCSurvival

Median survival 7.5 vs. 4.6 mos.; P = 0.011-year survival 37% vs. 12%; P = 0.003

100

80

60

40

20

0

90 3 6 12 15 18 21

Months

% S

urvi

val

Docetaxel 75 mg/m2

Best supportive care

Shepherd et al. J Clin Oncol. 2000;18:2095.

TAX 320B: Second-Line NSCLCSchema

Fossella et al. J Clin Oncol. 2000;18:2354.

Stage III/IV locally advanced or metastatic NSCLC

Stratified by:• Response to previous

platinum-based therapy• PS

N = 373

Arm A q 3wDocetaxel 75 mg/m2

N = 125

Arm B q 3wDocetaxel 100 mg/m2

N = 125

Arm C q 3wControl

Vinorelbine 30 mg/m2 days 1, 8, 15 or ifosfamide 2 mg/m2 days 1-3

N = 123

RANDOMIZE

Months

% S

urvi

val

100

80

60

40

20

0

0 3 6 9 12 15 18 21

Docetaxel 100 mg/m2

Docetaxel 75 mg/m2

Vinorelbine/ifosfamide

Docetaxel 75 mg/m2 vs. vinorelbine/ifosfamide1-year survival 30% vs. 20%; P=0.05, 2 Median 5.7 vs. 5.6 mos. (NS)

Docetaxel 100 mg/m2 vs. vinorelbine/ifosfamide1-year survival 23% vs. 20%Median 5.5 vs. 5.6 mos. (NS)

Docetaxel vs. Vinorelbine or Ifosfamide

TAX 320B: Second-Line NSCLCSurvival

NS = not significant. Fossella et al. J Clin Oncol. 2000;18:2354.

Pemetrexed vs. Docetaxelfor Second-Line NSCLC

Schema

Hanna et al. J Clin Oncol. 2004;22:1589.

Stage IIIB or IV NSCLC

Stratified by:• PS• Prior platinum or paclitaxel

therapy• Number of prior therapies• Best response to chemotherapy• Time since last chemotherapy• Geographic region

N = 571

Arm A q 3w Pemetrexed 500 mg/m2 day 1

N = 283

Arm B q 3wDocetaxel 75 mg/m2 day 1

N = 288

RANDOMIZE


Overall Survival (ITT)

ITT = intent to treatHR = hazard ratioCI = confidence intervalMST = median survival time

Sur

viva

l Dis

trib

utio

n

Months

0.00

0.25

0.50

0.75

1.00

0.0 2.5 5.0 7.5 10.0 12.5 15.0 17.5 20.0 22.5

MST 8.3 mos.1-yr OS: 29.7%

HR = 0.99

95% CI of HR (0.82, 1.20)

MST 7.9 mos.1-yr OS: 29.7%

Pemetrexed (N = 283)

Docetaxel (N = 288)


Pemetrexed vs. Docetaxelfor Second-Line NSCLCProgression-Free Survival (ITT)

ITT = intent to treatHR = hazard ratioCI = confidence intervalMPFS = median progression-free survival

0.00

0.25

0.50

0.75

1.00

0.0 2.5 5.0 7.5 10.0 12.5 15.0 17.5 20.0

Months

%

Pro

gres

sion

MPFS = 2.9 mos.

MPFS = 2.9 mos.

HR = 0.97

95% CI of HR (0.82, 1.16)


Docetaxel (N = 288)



Response Rates

46.445.8

9.1 8.8

0

5

10

15

20

25

30

35

40

45

50

CR and PR Stable Disease


Docetaxel (N = 274)

Per

cent

(%

)

[CI=5.9,13.2] [CI=5.7,12.8]



Hematological Toxicities

Pemetrexed Docetaxel

Grade 3/4 (% patients) (N = 265) (N = 276) P-value

Neutropenia 5.3 40.2 < .001

Febrile Neutropenia 1.9 12.7 < .001

Infect w/ Gr 3/4 Neutropenia 0 3.3 .004

Anemia 4.2 4.3 1.00

Thrombocytopenia 2 < 1 .116



Hospitalizations, Transfusions & Growth Factors

Pemetrexed Docetaxel (N = 265) (N = 276) P-value

Patients with ≥ 1 hosp. 31.7% 40.6% .032due to an adverse event

Total hospitalizations 1.5% 13.4% < .001 due to febrile neutropenia

G-CSF/GM-CSF 2.6% 19.2% < .001

Erythropoietin 6.8% 10.1% .169

Red blood cell 16.6% 11.6% .085transfusions


Phase III Trial of Erlotinib in Advanced NSCLC (BR.21): Schema

• Primary End Point: Overall survival

• Secondary: Time to deterioration, PFS, ORR, duration of response , QOL, safety

Erlotinib 150 mg/d+ best supportive care

N = 488

Placebo+ best supportive care

N = 243

RANDOMIZE

2:1 randomization to the experimental arm.

Stage IIIB/IV locally advanced or metastatic NSCLC

• PS 0-3• ≥1 failed prior chemotherapy regimen• ≥18 years• No prior HER1/EGFR inhibitors• No prior malignancies or uncontrolled

CNS metastasesStratified by

• Center• PS (0/1 vs 2/3)• Response to prior therapy

(CR/PR:SD:PD)• Prior regimens (1 vs 2)• Prior platinum (Yes vs No)

N=731

Shepard et al. J Clin Oncol. 2004; 22(suppl)622. Abstract 7022 and oral presentation.

Phase III Trial of Erlotinib in Advanced NSCLC (BR.21): Schema

• Primary End Point: Overall survival

• Secondary: Time to deterioration, PFS, ORR, duration of response , QOL, safety

Erlotinib 150 mg/d+ best supportive care

N = 488

Placebo+ best supportive care

N = 243

RANDOMIZE

2:1 randomization to the experimental arm.

Stage IIIB/IV locally advanced or metastatic NSCLC

• PS 0-3• ≥1 failed prior chemotherapy regimen• ≥18 years• No prior HER1/EGFR inhibitors• No prior malignancies or uncontrolled*

CNS metastasesStratified by

• Center• PS (0/1 vs 2/3)• Response to prior therapy

(CR/PR:SD:PD)• Prior regimens (1 vs 2)• Prior platinum (Yes vs No)

N=731

Shepard et al. J Clin Oncol. 2004; 22(suppl)622. Abstract 7022 and oral presentation.

POSITIVE

*Adjusted for stratification factors at randomization, and HER1/EGFR status.

BR.21: Overall Survival

42.5% improvement in median survival

HR = 0.73; P < 0.001*

Erlotinib(N = 488)

Placebo(N = 243)

Median survival (mos.) 6.7 4.7

1-year survival (%) 31 21

Months

% S

urvi

val

Erlotinib

Placebo

100

0 5 10 15 20 25 30

80

40

20

0

60

Adapted from Shepherd et al. J Clin Oncol. 2004;22(suppl):622. Abstract 7022 and oral presentation;Data on file, Genentech, Inc.

BR.21: Survival Across Subgroups

Circle size proportional to subset size.

0 1 2 3

All patients 731

PS 0-1 486

PS 2-3 245

Male 475

Female 256

<65 y 452

65 y 279

Adenocarcinoma 365

Squamous cell carcinoma 222

Other histology 144

Prior wt loss <5% 486

Prior wt loss 5%-10% 132

Prior wt loss >10% 81

Never smoked 146

Current/ex-smoker 545

1 prior regimen 364

2 prior regimens 367

Decreasedrisk of death

Increasedrisk of death

Subset n

Data on file, Genentech, Inc.

BR.21: Survival by Gender

Adapted from Shepherd et al. J Clin Oncol. 2004;22(suppl)622. Abstract 7022 and oral presentation;Data on file, Genentech, Inc.

Female

HR = 0.80 (95% CI, 0.59-1.07)RR = 14.4%

Months

% S

urvi

val

0 5 10 15 20 25

Placebo(N = 83)

Erlotinib(N = 173)

100

80

60

40

0

20

Male

HR = 0.76 (95% CI, 0.62-0.94)RR = 6.0%

MS: 5.7 vs. 4.5 mos.

Months

% S

urvi

val

0 5 10 15 20 25

Placebo(N = 160)

Erlotinib(N = 315)

100

80

60

40

0

20

BR.21: Survival by Histology

Squamous Cell Carcinoma

0 5 10 15 20 25

HR = 0.67 (95% CI, 0.50-0.90)RR = 3.8%

MS: 5.6 vs. 3.6 mos.

1.00

Months

0.75

0.50

0.25

0

Sur

viva

l dis

trib

utio

n fu

nctio

n

Placebo(N = 78)

Erlotinib(N = 144)

HR = 0.72 (95% CI, 0.56-0.92)RR = 13.9%

MS: 7.8 vs. 5.4 mos.

Adenocarcinoma

Months

Sur

viva

l dis

trib

utio

n fu

nctio

n

0 5 10 15 20 25

Placebo(N = 119)

Erlotinib(N = 246)

0

1.00

0.75

0.50

0.25


BR.21: Survival by Smoking History

Never Smoked

HR = 0.42 (95% CI, 0.28-0.64)RR = 24.7%

Months

% S

urvi

val

0 5 10 15 20 25

100

80

60

40

0

20

Placebo(N = 42)

Erlotinib(N = 104)

Current and Ex-smokers

HR = 0.87 (95% CI, 0.71-1.05)RR = 3.9%

Months

0 5 10 15 20 25

100

80

60

40

0

20

Placebo(N = 187)

Erlotinib(N = 358)

% S

urvi

val


ASCO 2007 – NSCLC

Commentary

Documents

Non-Small Cell Lung Cancer Corey J. Langer, MD, FACP Medical Director, Thoracic Oncology Fox Chase Cancer Center Philadelphia, PA