elderly and ps 2 patients with advanced nsclc winter lung cancer conference 2012

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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