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NSCLC Case PresentationHistory

• Male, 73 years old, smoker
• PS (ECOG) 2
• Major co-morbidities diabetes, peripheral
  neuropathy
• Hospitalized for right femur pain, cough

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RX Right femur hosteolysis
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NSCLC Case Presentation Staging

• Thoracic CT scan superior right lobe large
  lesion with controlateral mediastinal
  limphadenopathy
• Brain CT scan negative
• Abdominal CT scan left massive adrenal mass
• Bone scan multiple bone metastases
• Vertebral MNR no risk of vertebral fracture
• Stage IV

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Thoracic CT scan at diagnosis
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Abdominal CT scan at diagnosis
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Bone scan at diagnosis
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NSCLC Case Presentation Histological Diagnosis

• FNAB of adrenal mass malignant cells
• Cytological diagnosis epidermoid (NSCLC)

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Epidermoid carcinoma
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NSCLC Case Presentation

• Question 1
• Which first treatment (other then analgesics)?
• Palliative femur RT
• Chemotherapy
• Palliative femur RT diphosphonate
• Best Supportive Care alone

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NSCLC Case Presentation

• Question 1
• Which first treatment (other then analgesics)?
• Palliative femur RT
• Chemotherapy
• Palliative femur RT diphosphonate
• Best Supportive Care alone

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Zolendronic acid in the treatment of bone
metastases

• Lung cancer and other solid tumors

• Median time to first bone event (days)

• Placebo (n250)

• Zolendronate
• 4 mg (n257)

230

• p0,023

All tumors

163
100
200
300
Days
Rosen L et al CANCER 2004
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Zolendronic acid in the treatment of
bone metastases

• Lung cancer and other solid tumors

• Pathological fractures at 9 months zolendronate
  vs placebo

0,72

• Zolendronate

0,66

• Placebo

0,61
0,45
0,43
0,41

• Median number of events for patient

All tumors
Other tumors
Lung cancers
Rosen L et al CANCER 2004
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NSCLC Case Presentation

• Question 2
• Which subsequent therapy ?
• Thoracic RT
• Chemotherapy
• Best supportive care
• RT of adrenal metastasis

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NSCLC Case Presentation

• Question 2
• Which subsequent therapy ?
• Thoracic RT
• Chemotherapy
• Best supportive care
• RT of adrenal metastasis

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NSCLC Case Presentation

• Question 3
• Which chemotherapy ?
• Single agent vinorelbine
• Cisplatin-based chemotherapy
• Not platinum-based combination chemotherapy
• Single agent gemcitabine

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NSCLC Case Presentation

• Question 3
• Which chemotherapy ?
• Single agent vinorelbine
• Cisplatin-based chemotherapy
• Not platinum-based combination chemotherapy
• Single agent gemcitabine

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Thoracic CT scan after chemotherapy
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ELVIS STUDY
EORTC LC-13 QoL analysis
OVERALL SURVIVAL
Log-rank test P 0.03 Cox model P 0.02
IMPROVEMENT
WORSENING
Vinorelbine MS 6.5 months
Supportive care MS 4.8 months
Estimated effect of vinorelbine with 95 CI
Gridelli et al. J Natl Cancer Inst, 1999.
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MILES STUDY
Vinorelbine30 mg/m² D1, D8
Overall survival
Probability of survival
Gemcitabine1200 mg/m² D1, D8
R
GemcitabineVinorelbine NVB 25 mg/m² D1,
D8 Gem 1000 mg/m² D1, D8
Weeks
Gridelli C et al. J Natl Cancer Inst, 2003
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For elderly patients or patients with
ECOG/Zubrod performance status 2, available data
support the use of single-agent chemotherapy
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Retrospective analysis of Cooperative Group
trials on advanced NSCLC elderly patients
Author Group Trial
Treatments Langer, 2002
ECOG 5592 PE vs PTax vs
PTaxG-CSF Kelly, 2001 SWOG
9308-9509 P vs PV/ PV vs
CbTax Lilenbaum,2002 CALGB 9730
Tax vs CbTax Langer, 2003
ECOG 1594 PTax vs CbTax vs PG vs
PTxt Fossella, 2003 TAX 326
PV vs PTxt vs CbTxt
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CISPLATIN-BASED CHEMOTHERAPY WITH SPECIAL DOSES
OR SCHEDULE IN ADVANCED
NSCLC ELDERLY PATIENTS
Author Drugs N.pts
OR MS(mos) Feliu,2003 CDDPGEM
46 35 10.2
Lippe,2000 CDDPGEM 15
40 -
Berardi,2003 CDDPGEM 48
31.8 9 Mattioli, 2002
CDDPVNR 33 48
11 Ohe, 2004 CDDPTXT
33 52 15.8
Chen, 2006 CDDPTAX 41
39 10.5
CDDP 50 mg/m2 Q21 CDDP 35 mg/m2 wkly
CDDP 25 mg/m2 wkly CDDP 60 mg/m2 Q21
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Phase II trials of CDDP GEM or CDDP VNR in
advanced NSCLC elderly patients (MILES 02)
CDDP GEM CDDP 50-60-70
mg/m2, d 1 GEM 1000 mg/m2, d 1 - 8 R
every 3 wks
CDDP VNR CDDP 50-60-70 mg/m2, d
1 VNR 25 mg/m2, d 1 - 8
every 3 wks
Gridelli et al. ASCO 2006
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MILES 02 Summary Results
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Consensus on treatment in clinical practice

• Treatment options
• - single agent chemotherapy
• - platin-based doublets in fit (PS 0-1)
  patients selected for adequate organ
  function
• - supportive care

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Research QuestionsProposed Standard single
agent
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For elderly patients or patients with
ECOG/Zubrod performance status 2, available data
support the use of single-agent chemotherapy
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NSCLC PS 2 HeCOG Phase II randomised trial
R A N D O M I Z E
Carboplatin AUC 3 days 114 Gemcitabine 1250
mg/m2 days 114
A
B
Gemcitabine 1250 mg/m2 days 114
q 28 days Totally 4 cycles End point clinical
benefit
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Phase II randomized study of CBDCAGEM or GEM
in advanced NSCLC patients with PS 2
CT N.pts OR (ORSD)
MST (mos) G3

Neut PLT
GEM 47 4 (21)
4.8 2 0
or CBDCAGEM 43 14 (21)
6.7 7.5 7.5
No difference in term of clinical benefit
(primary endpoint)
Kosmidis PA et al, 2006
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ECOG 1599 PHASE II RANDOMIZED TRIAL OF
PLATIN-BASED CHEMOTHERAPY USING ATTENUATED DOSE
FOR ADVANCED NSCLC PS 2 PATIENTS
CDDP GEM CDDP 60 mg/m2, d1 GEM 1000
mg/m2, d1-8 NSCLC Q3 wks IIIB-IV PS
2 CBDCA TAX CBDCA AUC 6, d1 TAX 200
mg/m2/3h, d1 Q 3 wks
R
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ECOG 1599
Phase II randomized study of CBDCATaxol or
CDDPGEM in advanced NSCLC patients with PS 2
CT N.pts OR MST (mos)
Tox (all G4-5) CBDCATAX 51
25 6.2 39
or CDDPGEM 49 23
6.9 25
Langer C et al, J Clin Oncol 2007
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US phase III trial in advanced
NSCLC patients with PS2
CBDCAGEM
R
Pr. Objec t Survival N.pts 240
GEM
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Italian phase III Intergroup (CTPG,GOIRC,GOIM,GOL)
trial in advanced NSCLC patients
with PS2
CDDP GEM (ECOG 1599 schedule)
CDDP 60 mg/m2, d1 GEM 1000 mg/m2, d1-8/ q21
R
Pr. Object Survival N.pts 300
GEM 1200 mg/m2, d 1-8 q21
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Consensus on treatment in clinical practice

• Preferred option
• - new single agent chemotherapy (e.g.
  gemcitabine, vinorelbine, taxanes)
• Alternative options
• - carboplatin-based doublets
• - attenuated dose cisplatin-based doublets

Gridelli C et al, Ann Oncol 2004
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Research QuestionsProposed Standard single
agent
Gridelli C et al, Ann Oncol 2004
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NSCLC Case Presentation

• Question 4
• The patient achieved a partial response. Is a
  further treatment advisable?
• YES,different single agent chemotherapy
• NO
• YES, erlotinib
• YES,maintenance gemcitabine

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NSCLC Case Presentation

• Question 4
• The patient achieved a partial response. Is a
  further treatment advisable?
• YES,different single agent chemotherapy
• NO
• YES, erlotinib
• YES,maintenance gemcitabine

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The role of duration of chemotherapy in advanced
NSCLC
Author Drugs N.pts OR MST
Toxicity
neutr neur const Hb



G3-4 G2-4 G1-4 G3-4 Smit, 2001
MVP x 3 155 31 6
12 1 38 1
vs MVP x 6
153 38 7 48
0 50 4 Socinsky, CBDCATAX x 4
114 22 6.6 39 14 - 7 2001
vs CBDCA TAX to PD
116 24 8.5 42 27 - 10 Von
Plessen, CBDCAVNRX3 -
7 35
- - 3 2006
vs 300
CBDCAVNRX6
- 8 32
- - 9
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Results of a phase III trial on maintainance
single agent chemotherapy in advanced NSCLC
Author Drugs N.pts 1-yr S
Toxicity


G4 leuc Inf G5 Weestel,
2005 MIP 90 50.6 -
- - vs MIP VNR (wkly)
91 42.2 43.3
12.2 7.7 Belani,2005
CBDCATAX 141 50
- - -
vs
CBDCATAX
76
Overall G3-G4 45
TAX (wkly)
Krzakowski,2004 CDDPGEM
68 MS 11 mos
- - -
vs
CDDPGEM
138 MS 13 mos
- - -
GEM (1-8/21)
Not randomised but according to pts preference
Statistically not significant difference