Cyramza takes on Tarceva, but Tagrisso is the real opponent

It is all very well for Lilly’s VEGFR2 inhibitor Cyramza, given on top of Roche's Tarceva, to beat Tarceva alone in first-line EGFR-mutant lung cancer. But unless the drug can beat Astra’s Iressa follow-on, Tagrisso, the success – reported today from Lilly’s pivotal Relay trial – will count for very little. This is because as of last year Tagrisso has first-line EGFR-mutant NSCLC on its label, having roundly beaten Iressa or Tarceva in the Flaura trial, and is fast becoming the standard of care in this targeted setting. For a combo of Cyramza and Tarceva to make any headway with prescribers the Relay trial must show a median progression-free survival benefit in line with Tagrisso’s 18.9 months in Flaura; the full Relay data have not yet been revealed. Cyramza already has NSCLC on its label, but this is in the second-line setting, for people who have progressed on chemo or a relevant EGFR inhibitor. EvaluatePharma’s sellside consensus sees Cyramza selling just over $1bn in 2024, with NSCLC comprising 24% of this and gastric and colorectal cancers the remainder.

Landscape for selected small-molecule targeted NSCLC treatments
  Line of therapy/mutation  
Drug (company) 1st line 2nd line Note
Tarceva (Roche) EGFR+ EGFR+ Approved broadly, EGFR testing advised
Iressa (Astrazeneca) EGFR+   Exon 19 deletion or exon 21 substitution
Gilotrif (Boehringer Ingelheim) EGFR+   Broad EGFR+ label
Tagrisso (Astrazeneca) EGFR+ T790M+ T790M+ use is post EGFR TKI therapy
Vizimpro (Pfizer) EGFR+   Exon 19 deletion or exon 21 substitution
Cyramza (Lilly) + Tarceva EGFR+   Exon 19 deletion or exon 21 substitution
Poziotinib (Spectrum) EGFR+   Exon 20 mutation
Tepotinib (Merck KGaA)   c-Met+ Post EGFR TKI therapy
Capmatinib (Incyte)   c-Met+ Post EGFR TKI therapy
Savolitinib (Chi-Med/Astrazeneca)   c-Met+ Post EGFR TKI therapy
BLU-667 (Blueprint)   Ret+ Post EGFR TKI therapy
LOXO-292 (Lilly, ex Loxo)   Ret+ Post EGFR TKI therapy
SL-1001 (Stemline)   Ret+ Licensed from Cancer Research UK

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