www.esanum.it/cool
Afatinib BIBW 2992
LUX-Lung 1: Rationale
Presence of EGFR-activating mutation in NSCLC
confers exquisit...
www.esanum.it/cool
Trial design
Randomization
2 : 1
Oral BIBW 2992 50 mg once daily
plus best supportive care
Oral placebo...
www.esanum.it/cool
Demographics/prior treatment
www.esanum.it/cool
Disease control rate
and objective responses
Independent Investigator
Afatini
b (%)
Placeb
o
(%)
Afatin...
www.esanum.it/cool
www.esanum.it/cool
Waterfall plots by independent review
www.esanum.it/cool
PFS by independent review
Importante vantaggio sull’aumento del PFSImportante vantaggio sull’aumento de...
www.esanum.it/cool
PFS by
subgroups
Hazard ratio
← Favors afatinib Favors placebo →
www.esanum.it/cool
Overall survival
Nessun vantaggio in sopravvivenza
www.esanum.it/cool
1.077
1.168
1.020
1.109
1.005
1.056
1.152
1.160
1.034
1.023
1.200
2.188
0.806
1.016
1.154
1.243
1.035
1...
www.esanum.it/cool
Sopravvivenza e ulteriori trattamenti
Nessun trattamento ulteriore Ulteriori trattamenti
www.esanum.it/cool
Conclusions 1
Patient population was enriched as intended
LUX-Lung 1 did not meet its primary endpoint
...
www.esanum.it/cool
Conclusions 2
Significantly higher ORR and DCR on
afatinib
Clinically relevant improvement in pre-
spec...
www.esanum.it/cool
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Afatinib bibw 2992 nov 2010

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Afatinib bibw 2992 nov 2010

  1. 1. www.esanum.it/cool Afatinib BIBW 2992 LUX-Lung 1: Rationale Presence of EGFR-activating mutation in NSCLC confers exquisite sensitivity to EGFR TKIs Patients initially sensitive to gefitinib (G) or erlotinib (E) eventually progress Resistance T790M mutations are detected in ~50% of patients previously responsive to gefitinib/erlotinib Afatinib is an irreversible EGFR and HER2 inhibitor with preclinical activity against NSCLC with T790M mutations (EC50: 99 nM, NCI-1975) No approved therapy available for locally advanced or metastatic NSCLC in patients who have failed CT and progressed after treatment with EGFR TKI
  2. 2. www.esanum.it/cool Trial design Randomization 2 : 1 Oral BIBW 2992 50 mg once daily plus best supportive care Oral placebo once daily plus best supportive care N=585 Patients with: • Adenocarcinoma of the lung • Stage IIIB/IV • Progressed after one or two lines of chemotherapy (incl. one platinum- based regimen) and ≥12 weeks of treatment with erlotinib or gefitinib • ECOG 0–2 Primary endpoint: Overall survival (OS) Secondary: PFS, RECIST response, QoL, safety Countries: North America, Europe, AsiaCountries: North America, Europe, Asia Status: Recruitment complete, DBL for primary analysis 6 July 2010Status: Recruitment complete, DBL for primary analysis 6 July 2010
  3. 3. www.esanum.it/cool Demographics/prior treatment
  4. 4. www.esanum.it/cool Disease control rate and objective responses Independent Investigator Afatini b (%) Placeb o (%) Afatini b (%) Placebo (%) PR, regardless of confirmation PR, confirmed 13.3* 7.4 0.5** 0.5 14.1 10.8 0.5 0.5 SD 50.8 17.9 49.7 21.0 DCR (CR+PR+SD), confirmed 58.2 18.5 60.5 21.5 Median duration of response: 6 monthsMedian duration of response: 6 months * P < 0.01 compared to placebo ** P < 0.0001 compard to placebo
  5. 5. www.esanum.it/cool
  6. 6. www.esanum.it/cool Waterfall plots by independent review
  7. 7. www.esanum.it/cool PFS by independent review Importante vantaggio sull’aumento del PFSImportante vantaggio sull’aumento del PFS HR = 0.38
  8. 8. www.esanum.it/cool PFS by subgroups Hazard ratio ← Favors afatinib Favors placebo →
  9. 9. www.esanum.it/cool Overall survival Nessun vantaggio in sopravvivenza
  10. 10. www.esanum.it/cool 1.077 1.168 1.020 1.109 1.005 1.056 1.152 1.160 1.034 1.023 1.200 2.188 0.806 1.016 1.154 1.243 1.035 1.196 0.882 1.103 1.069 0.898 1.190 Hazard ratio OS by subgroups
  11. 11. www.esanum.it/cool Sopravvivenza e ulteriori trattamenti Nessun trattamento ulteriore Ulteriori trattamenti
  12. 12. www.esanum.it/cool Conclusions 1 Patient population was enriched as intended LUX-Lung 1 did not meet its primary endpoint of overall survival Unprecedented survival in both trial arms Considerable and unexpected use of further systemic treatments Afatinib significantly improved progression free survival (HR = 0.38) 2 months absolute increase in median PFS Robust effect across all subgroups Seen with both independent and investigator assessments
  13. 13. www.esanum.it/cool Conclusions 2 Significantly higher ORR and DCR on afatinib Clinically relevant improvement in pre- specified lung cancer related symptoms in the afatinib arm Safety profile of afatinib as expected: Diarrhea and rash managed effectively by dose interruption/reduction
  14. 14. www.esanum.it/cool

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