This is the largest prospective trial of bevacizumab in poor performance status patients with advanced nsclc

This is the largest prospective trial of bevacizumab in poor performance status patients with advanced NSCLC.

• This is the largest prospective trial of bevacizumab in poor performance status patients with advanced NSCLC.

• All three regimens were safe and well-tolerated.

• ORRs with Pem/Bev +/- Cb were encouraging and comparable to historical outcomes in patients with better performance status.

Unadjusted Kaplan–Meier estimates for OS among pts (A) <75 yrs and (B) ≥75 yrs receiving PC + Bev in the pooled population of E4599 and PointBreak relative to pts receiving PC alone in E4599

• Unadjusted Kaplan–Meier estimates for OS among pts (A) <75 yrs and (B) ≥75 yrs receiving PC + Bev in the pooled population of E4599 and PointBreak relative to pts receiving PC alone in E4599

This exploratory, pooled analysis of pt data from the E4599 and PointBreak studies demonstrated a statistically significant and clinically meaningful OS and PFS benefit with the addition of Bev to PC for all pts <75 yrs of age

• This exploratory, pooled analysis of pt data from the E4599 and PointBreak studies demonstrated a statistically significant and clinically meaningful OS and PFS benefit with the addition of Bev to PC for all pts <75 yrs of age

• No significant PFS or OS benefit was observed for pts ≥75 yrs of age receiving PC + Bev compared with PC alone

• Incidence of grade 5 events was 8% vs 2% for PC + Bev vs PC
• However, the small number of pts in this subgroup (n=157) may not allow firm conclusions to be made

• Outside of a clinical trial, clinicians must use careful judgment when administering Bev to pts ≥75 yrs with advanced NSCLC

Prespecified interim analysis of the BREC trial showed a detrimental effect in the experimental arm.

• Prespecified interim analysis of the BREC trial showed a detrimental effect in the experimental arm.

• BREC trial was prematurely closed

• Interaction between PS and treatment arm.

• Favorable non- significant effect for the experimental arm among patients with ECOG PS 0
• Significant increased risk of death in the experiental ar in atients with ECOG PS1

• We are currently examining alternative biomarkers that could elucidate DNA repair mechanisms.

OS data were still immature at the latest data cut-off

• OS data were still immature at the latest data cut-off

• ORR and DCR for the interim and updated analyses are shown

Meaningful treatment benefit was observed in both EGFR mutation type subgroups (exon 19 deletions and exon 21 L858R mutations), and was more marked in the exon 19 deletion subgroup

• Meaningful treatment benefit was observed in both EGFR mutation type subgroups (exon 19 deletions and exon 21 L858R mutations), and was more marked in the exon 19 deletion subgroup

These analyses demonstrate that erlotinib provides statistically significant and clinically meaningful improvement in investigator-assessed PFS, which was corroborated by IRC assessment, compared with GP in Asian patients with EGFR mutation-positive NSCLC

• These analyses demonstrate that erlotinib provides statistically significant and clinically meaningful improvement in investigator-assessed PFS, which was corroborated by IRC assessment, compared with GP in Asian patients with EGFR mutation-positive NSCLC

• Primary efficacy results were also supported by secondary endpoints including ORR and DCR, with no new safety concerns compared with previous studies of erlotinib

• These results support the data from other first-line studies in Asian populations, showing that erlotinib provides a PFS benefit over chemotherapy in this patient subgroup with EGFR mutation-positive NSCLC1,2

Largest prospective dataset in patients with uncommon EGFR mutations (n=75)

• Largest prospective dataset in patients with uncommon EGFR mutations (n=75)

• High heterogeneity within the subgroup with uncommon EGFR mutations

• Low response rate in patients with exon 20 insertions and T790M tumours

• Durable tumour control observed in some cases (PFS up to 13.8 months)

• Activity was observed in other exon 18 (G719X), 20 (S768I) and 21 (L861Q) mutations that are known to be less responsive to reversible EGFR TKIs

• Activity was in the range of efficacy observed with afatinib in common EGFR mutations