Research To Practice

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Elderly and PS 2 Patients With Advanced NSCLC
Winter Lung Cancer Conference2012

• Rogerio Lilenbaum, MD, FACP
• Cleveland Clinic Florida
• Weston, FL

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Elderly and PS 2 Patients With Advanced NSCLC

• Combination vs. Single Agent Therapy
• Bevacizumab with chemotherapy
• Targeted agents in unselected patients

6
IFCT Study Schema
R A N D O M
Stratification by center, PS 0-1 vs. 2, age 80
vs. gt80 and stage III vs. IV
Choice of the center at the beginning of the
study In case of PD or excessive toxicity
Ref Quoix E, Zalcman G, Oster JP, et al
Intergroupe Francophone de Cancérologie
Thoracique. Carboplatin and weekly paclitaxel
doublet chemotherapy compared with monotherapy in
elderly patients with advanced non-small-cell
lung cancer IFCT-0501 randomised, phase 3 trial.
Lancet. 2011 Sep 17378(9796)1079-88.
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PFS (ITT) Quoix et al

• Doublet chemotherapy
• Median PFS 6.1 months (95 CI 5.5-6.9)
• 1-year PFS 15.4 (95 CI 10.8-20.8)
• Monotherapy
• Median PFS 3.0 months (95 CI 2.6-3.9)
• 1-year PFS 2.3 (95 CI 0.8-5.3)
• p lt 10-6

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Overall survival (ITT) Quoix et al

• Doublet chemotherapy
• MST 10.3 months (95 CI 8.3-13.3)
• 1-year survival 45.1 (95 CI 38.2-51.8)
• Monotherapy
• MST 6.2 months (95 CI 5.3-7.4)
• 1-year survival 26.9 (95 CI 21-33.1)
• p 0.00004

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Exploratory Sub-group analysis
"Despite increased toxic effects, platinum-based
doublet chemotherapy was associated with survival
benefits compared with vinorelbine or gemcitabine
monotherapy in elderly patients with NSCLC."
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Brazilian PS2 NSCLC Trial Design
Pemetrexed 500 mg/m2 IV q 21 days (max 4 cycles)
R A N D O M I Z E
Chemotherapy-naive patients with stage IIIB (with
pleural effusion) or IV NSCLC and ECOG PS 2 N
208
Carboplatin AUC5 IV q 21 days Pemetrexed 500
mg/m2 IV q 21 days (max 4 cycles)
Primary Objective OS
Trial closed submitted to ASCO 2012
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Elderly and PS 2 Patients With Advanced NSCLC

• Combination vs. Single Agent Therapy
• Elderly Yes
• PS 2 TBD
• Bevacizumab with chemotherapy
• Targeted agents in unselected patients

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Elderly and PS 2 Patients With Advanced NSCLC

• Combination vs. Single Agent Therapy
• Bevacizumab with chemotherapy
• Targeted agents in unselected patients

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Outcomes for Elderly Advanced NSCLC Patients
Treated with Bevacizumab in Combination with
Carboplatin and Paclitaxel Analysis of ECOG 4599
Study
Elderly ( 70) Elderly ( 70) Non-Elderly (lt 70) Non-Elderly (lt 70)
PC PCB PC PCB
CRPR 17 29 14 36
SD 50 39 50 39
Median PFS 4.9 m 5.9 m P0.063 4.4 m 6.2 m Plt0.001
1-Yr Survival 50 46 42 53
Median survival 12.1 m 11.3 m P 0.4 9.6 m 12.8 m P 0.0027
Median Age Elderly 74
Ramalingan et al. JCO 2008
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Toxicity on PCB Arm Elderly vs. Non-Elderly
Grade 3/4 gt 70 yrs lt 70 yrs P
Neutropenia (Gr 4) 34 22 0.02
Melena/GI Bleed 3.5 0.9 0.005
Proteinuria 7.9 1.3 0.001
Motor neuropathy 3.5 0.6 0.05
Worst Grade 87 70 lt 0.001
TRDs 6.3 2.6 0.08
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Outcomes for Elderly Patients Treated With
Bevacizumab in Combination with Cisplatin and
Gemcitabine Analysis of the AVAIL Study
Elderly Group 65
Younger Group lt 65
CG N112 CGB 7.5 N89 CGB 15 N103 CG N-235 CGB 7.5 N256 CGB 15 N248
ORR 30 40 29 24 41 44
PFS 0.71 0.84 0.76 0.85
OS 0.84 0.88 0.98 1.09
Median Age Elderly Group 68 (36 70 or
older)
Results reported in HR
Leighl et al. JCO 2008
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Elderly Patients Toxicity Analysis of the AVAIL
Study
Only Gr3 PLT more frequent with Bev . Post Hoc
analysis of 70 vs. 70 similar to age 65 cutoff

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Bev in PS 2 Advanced NSCLC TOPPS
Pemetrexed 500 mg/m2 IV q 21 days
R A N D O M I Z E
Chemotherapy-naive patients with stage IIIB (with
pleural effusion) or IV NSCLC and ECOG PS 2
Pemetrexed 500 mg/m2 IV q 21 days Bevacizumab 15
mg/kg IV q 21 days
Carboplatin AUC5 IV q 21 days Pemetrexed 500
mg/m2 IV q 21 days Bevacizumab 15 mg/kg IV q 21
days
Primary Objective PFS Secondary
ObjectivesORR Toxicity OS
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Elderly and PS 2 Patients With Advanced NSCLC

• Combination vs. Single Agent Therapy
• Bevacizumab with chemotherapy
• Age alone is not a contraindication to Bev
• Exercise caution with very old patients and/or
  those with significant co-morbidities or
  compromised PS
• Targeted agents in unselected patients

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Elderly and PS 2 Patients With Advanced NSCLC

• Combination vs. Single Agent Therapy
• Bevacizumab with chemotherapy
• Targeted agents in unselected patients

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Erlotinib or Chemotherapy in PS2 Patients
Arm E 52 CP 51
OOR () 4 12
SD () 37 43
PD () 44 20
PFS (mo) 1.9 3.5
MST (mo) 6.6 9.5
1y OS () 21 45
Lilenbaum et al. JCO 2008
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TOPICAL

Endpoints

• Inclusion criteria
• Histologically/cytologically confirmed NSCLC
• Measurable stage IIIB/IV disease and 18 yrs
• Chemo-naive and unsuitable for chemotherapy
  ECOG PS 23 or PS 01 with impaired renal
  function CClt60ml/min
• Life expectancy 8 weeks

Erlotinib(150mg/day)to PD

• Primary
• Overall survival (OS)
• Secondary
• Progression-free survival (PFS)
• Objective response rate
• Quality of life (QoL)
• Disease-related symptoms
• Safety and tolerability
• Translational
• Biomarker analyses
• EGFR mutation proteomic/genomic markers

11 randomization
Placeboto PD
/- palliative XRT
Lee SM et al ASCO 2010
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Baseline characteristics
Erlotinib (n350) Placebo (n320)
Age, median (range), years 77.4 (4291) 77.2 (4591)
Male / female, 61 / 39 61 / 39
Stage IIIB / IV, 36 / 64 33 / 67
ECOG PS 01 / 2 / 3, 16 / 55 / 29 16 / 56 / 28
Adeno / squamous cell / large cell / other, 38 / 38 / 4 / 20 38 / 40 / 5 / 17
Caucasian / Asian / other, 96 / 2 / 2 98 / 1 / 1
Current / ex- / never smoker, 36 / 59 / 5 37 / 57 / 6
Pack-years (current/ex-smoker), median (range) 40 (1220) 38 (1130)
Median time since cessation (ex-smoker), years 18 17
Asian East, Southeast, South Asia other
African-Caribbean
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TOPICAL Trial
Arm E 350 P 320
PFS (m) 2.8 mo 2.7 mo
PFS (6mo) 22 13
PFS (1y) 9 4
OS (m) 3.8 mo 3.6 mo
OS (6mo) 36 33
OS (1y) 16 14
Lee et al. ASCO 2010
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OS planned subgroups

• Overall, erlotinib plus BSC did not improve OS
• Clear effect on OS for females

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Elderly and PS 2 Patients With Advanced NSCLC

• Combination vs. Single Agent Therapy
• Bevacizumab with chemotherapy
• Targeted agents in unselected patients
• First-line use of TKIs should be based on
  molecular selection
• Consider erlotinib in female patients with
  adenocarcinoma, if the alternative is no therapy

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Saturday, February 11, 2012Hollywood, Florida
Co-Chairs Rogerio C Lilenbaum, MD Mark A
Socinski, MD
Co-Chair and Moderator Neil Love, MD

Faculty
Chandra P Belani, MD John Heymach, MD, PhD Pasi A
Jänne, MD, PhD
Thomas J Lynch Jr, MD Heather Wakelee, MD