Treatment of the relapsed patient with advanced NSCLC

1
Treatment of the relapsed patient with advanced
NSCLC

• Luis Paz-Ares Rodríguez
• Hospital Universitario Virgen del Rocio,
  Seville, Spain

2
Objectives

• Consider the various options for second-line
  treatment of advanced NSCLC, through the use of a
  real-life case
• Compare the characteristics of second-line
  therapy
• efficacy
• tolerability
• quality of life (QoL)
• cost-effectiveness
• convenience

3
Patient history
Case history

• 60-year-old male
• Caucasian
• Prior smoker (10 pack/years)
• November 2003
• ULL NSCLC (large-cell carcinoma)
• stage IV (lung, nodes, bone, skin)

4
First-line therapy
Case history

• February 2004
• 1 cycle of carboplatin/gemcitabine
• toxicity cutaneous vasculitis
• March June 2004
• 4 cycles of carboplatin/paclitaxel
• toxicity alopecia, mild myalgia, paraesthesia
• partial response

5
Relapse after first-line therapy
Case history

• December 2004
• disease relapse
• subcutaneous lesions, lymph nodes
• back pain, PS 1

6
Second-line treatment options

• Chemotherapy
• Docetaxel
• Pemetrexed

• Targeted therapy
• Tarceva
• Gefitinib not licensed in EU

• Other options
• Best supportive care (BSC)
• Clinical trial

7
Selecting a second-line therapy

• Efficacy

8
Efficacy in phase III registration studies
PS ?2 and 12 prior regimens PS ?2 and 1 prior
regimen PS ?3 and 12 prior regimens p0.010
plt0.001

• In phase III study, gefitinib did not
  significantly improve survival compared with
  placebo

Ramalingam S, Sandler AB. Oncologist
20061165565
9
Can patients be rationally selected for specific
therapies?

• Similar efficacy for all approved second-line
  options
• can we select patients most likely to benefit
  from specific therapies?
• Answer not at present
• Current decisions made primarily on the basis of
  exclusion

• Chemotherapy
• No molecular predictors of benefit
• Exclude elderly??
• Exclude poor PS?

• Tarceva
• No proven molecular predictors of benefit
• Benefit observed in almost all subgroups

• Should chemotherapy be the default treatment in
  patients with good PS?

10
Median survival for patients with PS 0/1 in the
second-line setting
10 8 6 4 2 0
9.4
9.4
9.1
Median survival (months)
Docetaxel
Pemetrexed
Tarceva
Ramalingam S, Sandler AB. Oncologist
20061165565
11
BR.21 overall survival in patients with PS 0/1
who received second-line therapy
1.00 0.75 0.50 0.20 0
HR0.676 (95 CI 0.4930.927)
Survival probability
0 6 12 18 24
Survival (months)
OSI Pharmaceuticals and F. Hoffmann-La Roche
data on file
12
Selecting a second-line therapy

• Tolerability

13
Haematological toxicity in phase III studies
1Ramalingam S, Sandler AB. Oncologist
200611655652Shepherd FA, et al. N Engl J Med
2005353123323Tarceva Summary of Product
Characteristics, F. Hoffman-La Roche, 2007
14
Non-haematological toxicity in phase III studies
Ramalingam S, Sandler AB. Oncologist
20061165565
15
Selecting a second-line therapy

• QoL considerations

16
Tarceva increases time to deterioration of common
advanced NSCLC symptoms
p0.04
6 4 2 0
p0.04
4.9
4.7
3.7
p0.03
Median time to deterioration (months)
2.9
2.8
1.9
n298
n153
n353
n179
n348
n179
Cough
Dyspnoea
Pain
Bezjak A, et al. J Clin Oncol 20062438317 Sheph
erd FA, et al. N Engl J Med 200535312332
17
Significant improvements in QoL with Tarceva
(EORTC QLQ-C30)
?10 point change from baseline at anytime
(clinically significant) p?0.01
Bezjak A, et al. J Clin Oncol 20062438317
18
Symptom and QoL outcomes in docetaxel versus BSC
study (TAX317)

• Lung Cancer Symptom Scale (LCSS)
• Trends in observer-rated fatigue, pain and
  overall LCSS score favouring docetaxel overall
• No significant improvements in QoL for 75mg/m2
  dose

Dancey J, et al. Lung Cancer 20044318394
19
Symptom outcomes in pemetrexed versus docetaxel
study (JMEI)

• Rate of change in average symptom burden index of
  LCSS

40 30 20 10 0
Docetaxel (n247) Pemetrexed (n227)
Patients ()
Improved
Worsened
Stable
Other

• No significant difference between treatments
  across all categories (p0.1447 Mantel-Haenszel
  c2 test)

Hanna N, et al. J Clin Oncol 200422158997
20
Selecting a second-line therapy

• Cost-effectiveness

21
Cost-effectiveness studies forsecond-line
therapies

• Docetaxel
• cost-effective versus BSC (Canada, UK)1,2
• Pemetrexed
• cost-effective versus docetaxel (UK)3
• Tarceva
• cost-effective versus BSC (Canada, The
  Netherlands)4,5
• cost-saving versus docetaxel (Germany, The
  Netherlands, Poland, Spain, UK)4,69
• cost-saving versus pemetrexed (Germany, Poland,
  Spain)68

1Leighl NB, et al. J Clin Oncol 200220134452
2Holmes J, et al. Pharmacoeconomics
2004225819 3Bhalla S, et al. J Clin Oncol
200725(Suppl. 18 Pt I)332s (Abs. 6540) 4Côté
I, et al. Value Health 20069A279 5Pompen M, et
al. Value Health 20069A203 6Gabriel A, et al.
Value Health 20069A278 7Orlewska E, et al.
Value Health 20069A2798Rubio Terres C, et al.
Value Health 20069A2834 9Lewis G, et al.
Value Health 20069A2034
22
Selecting a second-line therapy

• Convenience

23
Convenience considerations
Ramalingam S, Sandler AB. Oncologist
20061165565
24
Selecting a second-line therapy

• Patient preference

25
Patient preference

• All treatment decisions should be made in
  consultation with the patient
• patient has final decision
• Patients may be unwilling to receive a second
  line of chemotherapy because of toxicity concerns
• Patients may prefer an oral therapy that can
  beself-administered at home

26
Case study selection of second-line therapy
Case history

• Tarceva
• efficacious treatment
• prior toxicity (neuropathy) with chemotherapy
• patient preference for an oral treatment

27
Outcome of patient on Tarceva therapy
Case history

• Response PR
• Duration 19 months
• Toxicity mild rash, paronychia
• QoL able to resume work

28
Third-line treatment
Case history

• Patient was offered pemetrexed as third-line
  treatment
• 6 courses from October 2006
• toxicity rash, asthaenia
• minor remission (9 months)

29
Conclusions

• Selection of the treatment for a specific patient
  is based on a balance of several factors,
  particularly
• efficacy
• tolerability
• QoL benefits
• Tarceva is the only EGFR inhibitor to have shown
  a survival benefit in previously treated advanced
  NSCLC
• similar efficacy to chemotherapy
• no haematological toxicity rash and diarrhoea
  generally mild/moderate and easily managed
• significant QoL benefits
• cost-effective
• convenient