Osimertinib in the treatment of non-small-cell lung cancer: design, development and place in therapy

Figures & data

Figure 1 EGFR pathway and mechanism of action of osimertinib.

Abbreviation: EGFR, epidermal growth factor receptor; TGF, transforming growth factor.

Table 1 AURA clinical trials

Trial	Phase	No. of patients	mPFS (months)	RR (%)	OS (months)
AURA	I/II	253: - 31 (dose-escalation cohorts) - 222 (dose-expansion cohorts): - 138: T790M + - 62: T790M − - 22: T790M unknown	- T790M + : 9.6 (95% CI 8.3–NR); - T790M − : 2.8 (95% CI 2.1–4.3)	- T790M + : 61 (95% CI 52–70); - T790M − : 21 (95% CI 12–34)	–
AURA2	II	210	9.9 (95% CI 8.5–12.3)	70 (95% CI 64–77)	1-year OS rate: 81% (95% CI 75–86)
AURA extension	II	411 (T790M +)	12.3 (95% CI 9.5–13.8)	62 (95% CI 54–68)	1-year OS rate: 79% (95% CI 72–84)
AURA3	III	416: - experimental arm (279) - chemotherapy arm (140)	10.1 (95% CI 8.3–12.3) 4.4 (95% CI 4.2–5.6) HR 0.30; (95% CI 0.23–0.41; p<0.001)	71 (95% CI 65–76] 31 (95% CI 24–40) Odds ratio 5.39; 95% CI 3.47–8.48; p<0.001	–

Notes: ‘–’ indicates not reported.

Abbreviations: HR, hazard ratio; NR, not reached; OS, overall survival; PFS, progression-free survival; RR, response rate.

Figure 2 ctDNA genotyping for EGFR T790M.

Abbreviations: EGFR, epidermal growth factor receptor; TKIs, tyrosine kinase inhibitors.

Figure 3 Mechanisms of resistance to third-generation EGFR TKI osimertinib.

Abbreviations: EGFR, epidermal growth factor receptor; TKIs, tyrosine kinase inhibitors.

Table 2 Third-generation EGFR TKIs in clinical development in NSCLC

Agents	Binding mode	Selectivity	Status
Osimertinib (AZD9291)	Irreversible	EGFR TKI-sensitizing mutations and T790M	Approved, T790M +
Rociletinib (CO-1686)	Irreversible	EGFR TKI-sensitizing mutations and T790M	No longer in development
Olmutinib (BI1482694/HM61713)	Irreversible	EGFR TKI-sensitizing mutations and T790M	Approved (only South Korea), T790M +
ASP8273	Irreversible	EGFR TKI-sensitizing mutations and T790M	Phase II, Phase III
Nazartinib (EGF816)	Irreversible	EGFR TKI-sensitizing mutations and T790M	Phase I/II, Phase II
PF-06747775	Irreversible	EGFR TKI-sensitizing mutations and T790M	Phase I/II
Avitinib (AC0010)	Irreversible	EGFR TKI-sensitizing mutations and T790M	Phase I/II

Abbreviations: EGFR, epidermal growth factor receptor; NSCLC, non-small-cell lung cancer; TKI, tyrosine kinase inhibitor.