NSCLC: AURA3 trial

Abbreviations

No EU-CTR

  • AURA3 references
    2017-02-16
    T.S. Mok
    Osimertinib or Platinum–Pemetrexed in EGFR T790M–Positive Lung Cancer
Investigated (inv)
Comparator (comp)

OSIM

peme+plt

279

140

Phase:

3

Randomisation:

Open label

Primary tumour:

NSCLC

Subtype (biomarker):

T790M

Stage:

meta

Line of therapy:

L2

Primary
OSIM
peme+plt
HR
p
PFS
10.1 mo
4.4 mo
0.30 (0.23-0.41)
<0.001
Secondaries
OSIM
peme+plt
HR
p
ORR
71%
31%
<0.001
PR
69%
30%
Time to response
6.1 w
6.4 w
DoR
9.7 mo
4.1 mo
(all grades, %)
OSIM
peme+plt
p
Any AE gr. ≥3
23%
47%
NA
Diarrhea
41
11
NA
Rash
34
6
NA
Dry skin
23
4
NA
Paronychia
22
1
NA
Nausea
16
49
NA
Vomiting
11
20
NA
Thrombocytopenia
10
20
NA
Neutropenia
8
23
NA
Anemia
8
30
NA
Asthenia
7
15
NA
ALT elevation
6
11
NA
AST elevation
5
11
NA
Malaise
4
10
NA
  • Inclusion
  • Exclusion

- Subjects with histologically or cytologically documented NSCLC. - Locally advanced or metastatic NSCLC - Radiological documentation of disease progression following 1st line EGFR TKI Treatment without any further treatment - Eligible to receive treatment with the selected doublet-chemotherapy - Central confirmation of T790M+ mutation status - World Health Organization (WHO) performance status 0-1 - At least one lesion, not previously irradiated.

- Prior neoadjuvant or adjuvant chemotherapy treatment within 6 months prior to starting 1st EGFR TKI treatment - Treatment with more than one prior line of treatment for advanced NSCLC - Treatment with an approved EGFR-TKI (e.g. erlotinib, gefitinib, afatinib) within 8 days or approximately 5x half-life of the first dose of study treatment - Any investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment - Previous treatment with Osimertinib, or a 3rd generation EGFR TKI For subjects who cross over to Osimertinib: - Once subjects on the platinum-based doublet chemotherapy arm are determined to have objective radiological progression according to RECIST 1.1 by the investigator and confirmed by an independent central imaging review. - At least 14 days since the last dose of platinum-based doublet chemotherapy.

Characteristics
OSIM
peme+plt
Agedc-comma sex
Median age (range) yr
62 (25–85)
63 (20–90)
Female - no.(%)
172 (62)
97 (69)
Race - no.(%)
White
89 (32)
45 (32)
Asian
182 (65)
92 (66)
Other
8 (3)
3 (2)
Disease classification - no.(%)
Adenocarcinoma histology not otherwise specified
232 (83)
122 (87)
Metastatic disease
266 (95)
138 (99)
CNS metastases
93 (33)
51 (36)
Extrathoracic visceral metastases
145 (52)
80 (57)
Type of EGFR mutation - no.(%)
T790M
275 (99)
138 (99)
Exon 19 deletion
191 (68)
87 (62)
Exon 21 L858R
83 (30)
45 (32)
G719X
4 (1)
2 (1)
Type of EGFR mutation - no.(%)
S768I
1 (<1)
1 (1)
Exon 20 insertion
1 (<1)
2 (1)
Previous anticancer regimens for advanced disease - no.(%)
1
269 (96)
134 (96)
2
9 (3)
6 (4)
3
1 (<1)
0
Previous EGFR-TKI therapy - no.(%)
Gefitinib
166 (59)
87 (62)
Erlotinib
96 (34)
49 (35)
Afatinib
20 (7)
4 (3)
Any EGFR-TKI
279 (100)
139 (99)
Ad-hoc:
no.pts inv.
no.pts comp.
OSIM
peme+plt
HR
p
PFS pts. CNS metastasis
93
51
8.5 mo.
4.2 mo.
0.32 (0.21-0.49)
na
PFS T790M tumor & plasma
116
56
8.2
4.2
0.42 (0.29-0.61)
na
  • PFS
analisys of PFS
OSIM
peme+plt
HR (95% CI)
Age (n)
<65 yr (242)
0.38 (0.28–0.54)
≥65 yr (177)
0.34 (0.23–0.50)
Sex (n)
Male (150)
0.43 (0.28–0.65)
Female (269)
0.34 (0.25–0.47)
EGFR-TKI–sensitizing mutation (n)
Exon 19 deletion (279)
0.34 (0.24–0.46)
L858R (128)
0.46 (0.30–0.71)
Duration of previous EGFR-TKI therapy (n)
<6 mo (24)
NC
≥6 mo (395)
0.39 (0.30–0.51)
CNS metastases (n)
Yes (144)
0.32 (0.21–0.49)
No (275)
0.40 (0.29–0.55)
Smoking history (n)
Yes (136)
0.40 (0.27–0.62)
No (283)
0.36 (0.26–0.49)
Race (n)
Asian (274)
0.32 (0.24–0.44)
Non-Asian (145)
0.48 (0.32–0.75)
analisys of
OSIM
peme+plt
HR (95% CI)