Differential impact of single agent erlotinib in patients with advanced or metastatic NSCLC untreate

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Differential impact of single agent erlotinib in
patients with advanced or metastatic NSCLC
untreated or pretreated with chemotherapy
univariate and multivariate analysis ESMO Abst
No.721OIstambul 2nd October 2006

• F. Cardenal, H.Cortés, R.Colomer, P.Garrido, A.
  Velasco, C.Pallarés, A.Gúrpide, M.Cobo, M.L
  Amador, and B. Massutí
• Institut Català dOncologia. H. Duran i Reynals,
  LHospitalet de Llobregat, Spain

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Background

• Erlotinib has proven efficacy and a favourable
  safety profile in chemotherapy pretreated
  patients with advanced NSCLC
• A clinical trial (TARGET) was run in Spain to
  assess the efficacy and safety of erlotinib in a
  very large population of unselected advanced
  NSCLC patients who were chemonaive or had already
  received chemotherapy
• Female sex, adenocarcinoma, Asiatic origin and
  never having smoked have been reported as
  predictors of favourable outcome to TKIs

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Background

• An analysis of recognized clinical predictors of
  outcome is presented. Line of treatment has
  been studied as another putative predictive factor

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Study design

• Phase II multicentric, prospective,
  non-randomized trial of Erlotinib in advanced
  NSCLC patients (IIIB-IV) pretreated with
  chemotherapy or untreated patients that were not
  suitable for first line standard chemotherapy
• Treatment
• Erlotinib single agent 150 mg/day po until
  disease progression or withdrawal dose
  modification allowed based on toxicity
• Clinical, biochemical, and radiologic evaluations
  were performed every 4 weeks. CT response
  assessment every 8 weeks

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Objectives

• Primary
• Time to disease progression
• Secondary
• Disease control rate (complete response
  partial response stable disease )
• Overall survival
• Quality of life
• Safety profile

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Selection criteria

• Advanced stage IIIB or IV, histologically proven
  NSCLC
• Age gt 18 years
• Previously treated with chemotherapy for advanced
  disease, deemed non suitable for standard
  chemotherapy
• Measurable or evaluable disease was not necessary
• ECOG PS 0-2
• Adequate blood counts and hepatic and renal
  function
• Patients with stable CNS metastases
• Written informed consent
• Amendment March 2005 Untreated patients with
  known EGFR mutation

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Patients characteristics (I)
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Patients characteristics (II)
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Response rate (n700) RECIST Criteria
ORR (95CI) 17 (15-21)
DCR(95CI) 58 (54-62)
RECIST Response Evaluation Criteria in Solid
Tumor Disease control rate Complete response
Partial response Stabilization ORR Overall
Response Rate
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Response rate analysis
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Time to progressionTotal population N1252
Median TTP 3,6 m 95 CI 3,2-4,1
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Time to progression analysis
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Overall survival Total population N1265
Median OS 5,8 m 95 CI 5,2-6,3 1-year survival
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Overall survival analysis
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Patients characteristics (I) (1st line Vs 2nd-3rd
line)
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Patients characteristics (II) (1st line Vs
2nd-3rd line)
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Adverse events (N1018)
6 of patients discontinued treatment because of
toxicity
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Conclusions

• These interim efficacy and safety results of
  Erlotinib in a real-life clinical setting in a
  large number of unselected patients with advanced
  NSCLC confirm the activity and favorable toxicity
  profile of erlotinib.
• Significantly higher response rates were observed
  in women, adenocarcinoma, never smoker and
  chemonaïve,although sex is not an independent
  predictor of response
• Never having smoked is the strongest independent
  predictor of longer time to progression.
• Never having smoked and good PS are strong
  predictors of longer survival

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Conclusions

• Adenocarcinoma histology is an independent
  predictor of longer time to progression and
  survival
• Line of treatment with erlotinib was an
  independent predictor of response and time to
  progression but not survival. Controlled trials
  are necessary to ascertain the influence of line
  of treatment on outcome.
• Although only 70 of the patients have been
  analyzed, final results for the studied outcomes
  might be very similar.The analysis of QoL will be
  interesting and is still pending

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Acknowledgements

• Investigators, co-investigators, research nurses
  and data managers from 108 centers all arround
  Spain
• Roche Farma, Spain
• To all patients and relatives