Upload
taro
View
28
Download
0
Embed Size (px)
DESCRIPTION
- PowerPoint PPT Presentation
Citation preview
Please note, these are the actual video-recorded proceedings from the live CME event and may include the use of trade names and other raw,
unedited content. Select slides from the original presentation are omitted where Research To
Practice was unable to obtain permission from the publication source and/or author. Links to view the actual reference materials have been provided for
your use in place of any omitted slides.
Elderly and PS 2 Patients With Advanced NSCLC
Winter Lung Cancer Conference2012
Rogerio Lilenbaum, MD, FACPCleveland Clinic Florida
Weston, FL
Elderly and PS 2 Patients With Advanced NSCLC
• Combination vs. Single Agent Therapy
• Bevacizumab with chemotherapy
• Targeted agents in unselected patients
IFCT Study Schema
*Choice of the center at the beginning of the study; ** In case of PD or excessive toxicity
NSCLCStage III-IVAge 70-89
yearsPS 0-2 n = 451
Vinorelbine or
Gemcitabine*
Carboplatin + paclitaxel
Erlotinib**150 mg/d
RANDOM
Stratification by center, PS 0-1 vs. 2, age ≤80 vs. >80 and stage III vs. IV
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 17;378(9796):1079-88.
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 < 10-6
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
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."
Brazilian PS2 NSCLC: Trial Design
Chemotherapy-naivepatients with stage IIIB (with pleural effusion)
or IV NSCLC and ECOG PS 2
N= 208
RANDOMIZE
Pemetrexed 500 mg/m2 IV q 21 days(max 4 cycles)
Carboplatin AUC=5 IV q 21 days Pemetrexed 500 mg/m2 IV q 21 days(max 4 cycles)
Primary Objective: OS
Trial closed – submitted to ASCO 2012
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
Elderly and PS 2 Patients With Advanced NSCLC
• Combination vs. Single Agent Therapy
• Bevacizumab with chemotherapy
• Targeted agents in unselected patients
Outcomes for Elderly Advanced NSCLC Patients Treated with Bevacizumab in Combination with Carboplatin and Paclitaxel:
Analysis of ECOG 4599 Study
Elderly (≥ 70)* Non-Elderly (< 70)PC PCB PC PCB
CR+PR 17% 29% 14% 36%
SD 50% 39% 50% 39%Median
PFS 4.9 m 5.9 mP=0.063 4.4 m 6.2 m
P<0.0011-Yr
Survival 50% 46% 42% 53%
Median survival 12.1 m 11.3 m
P = 0.4 9.6 m 12.8 mP = 0.0027
Ramalingan et al. JCO 2008
*Median Age “Elderly”: 74
Toxicity on PCB Arm: Elderly vs. Non-Elderly
Grade 3/4 > 70 yrs < 70 yrs PNeutropenia (Gr 4) 34% 22% 0.02Melena/GI Bleed 3.5% 0.9% 0.005
Proteinuria 7.9% 1.3% 0.001Motor neuropathy 3.5% 0.6% 0.05Worst Grade 87% 70% < 0.001TRDs 6.3% 2.6% 0.08
Outcomes for Elderly Patients Treated With Bevacizumab in Combination with Cisplatin and
Gemcitabine: Analysis of the AVAIL Study
CGN=112
CGB – 7.5
N=89
CGB – 15
N=103
CGN-235
CGB – 7.5
N=256
CGB – 15
N=248ORR 30% 40% 29% 24% 41% 44%PFS 0.71 0.84 0.76 0.85OS 0.84 0.88 0.98 1.09
Leighl et al. JCO 2008
*Median Age Elderly Group: 68 (36% 70 or older)
Elderly Group ≥ 65* Younger Group < 65
Results reported in HR
Elderly Patients : Toxicity Analysis of the AVAIL Study
Only Gr≥3 PLT more frequent with Bev . Post Hoc analysis of ≥ 70 vs. 70 similar to age 65 cutoff
Bev in PS 2 Advanced NSCLC: TOPPS
Chemotherapy-naivepatients with stage IIIB (with pleural effusion)
or IV NSCLC and ECOG PS 2
RANDOMIZE
Pemetrexed 500 mg/m2 IV q 21 days
Carboplatin AUC=5 IV q 21 days Pemetrexed 500 mg/m2 IV q 21 daysBevacizumab 15 mg/kg IV q 21 days
Primary Objective: PFS Secondary Objectives:ORRToxicityOS
Pemetrexed 500 mg/m2 IV q 21 daysBevacizumab 15 mg/kg IV q 21 days
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
Elderly and PS 2 Patients With Advanced NSCLC
• Combination vs. Single Agent Therapy
• Bevacizumab with chemotherapy
• Targeted agents in unselected patients
Erlotinib or Chemotherapy in PS2 Patients
Arm E = 52 CP = 51OOR (%) 4 12SD (%) 37 43PD (%) 44 20PFS (mo) 1.9 3.5MST (mo) 6.6 9.51y OS (%) 21 45
Lilenbaum et al. JCO 2008
TOPICAL
Erlotinib*(150mg/day)
to PD
Placebo*to PD
1:1 randomization
Inclusion criteria• Histologically/cytologically
confirmed NSCLC
• Measurable stage IIIB/IV disease and ≥ 18 yrs
• Chemo-naive and unsuitable for chemotherapy:– ECOG PS 2–3 or– PS 0–1 with impaired renal function CC<60ml/min
• Life expectancy ≥8 weeks
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
Endpoints
*+/- palliative XRT
Lee SM et al ASCO 2010
Erlotinib (n=350)
Placebo (n=320)
Age, median (range), years 77.4 (42–91) 77.2 (45–91)
Male / female, % 61 / 39 61 / 39
Stage IIIB / IV, % 36 / 64 33 / 67
ECOG PS 0–1 / 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 (1–220) 38 (1–130)
Median time since cessation (ex-smoker), years 18 17
Baseline characteristics
*Asian = East, Southeast, South Asia; other = African-Caribbean
TOPICAL Trial
Arm E = 350 P = 320PFS (m) 2.8 mo 2.7 moPFS (6mo) 22% 13%PFS (1y) 9% 4%OS (m) 3.8 mo 3.6 moOS (6mo) 36% 33%OS (1y) 16% 14%
Lee et al. ASCO 2010
OS: planned subgroups
• Overall, erlotinib plus BSC did not improve OS
• Clear effect on OS for females
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
Saturday, February 11, 2012Hollywood, Florida
Faculty
Co-ChairsRogerio C Lilenbaum, MDMark A Socinski, MD
Co-Chair and ModeratorNeil Love, MD
Chandra P Belani, MDJohn Heymach, MD, PhDPasi A Jänne, MD, PhD
Thomas J Lynch Jr, MDHeather Wakelee, MD