NSCLC: ADAURA trial

Abbreviations

No EU-CTR

  • ADAURA references
    2020-10-29
    Yi‑Long Wu
    Osimertinib in Resected EGFR-Mutated Non–Small-Cell Lung Cancer
Investigated (inv)
Comparator (comp)

OSIM

PLB

339

343

Phase:

3

Randomisation:

Double blind

Primary tumour:

NSCLC

Subtype (biomarker):

EGFR MT

Stage:

early

Line of therapy:

ADJ

Primary
OSIM
PLB
HR
p
DFS II-IIIA @2yr
90%
44%
0.17 (0.11-0.26)
<0.001
Secondaries
OSIM
PLB
HR
p
DFS IB-IIIA @2yr
89%
52%
0.20 (0.14-0.30)
<0.001
DFS all w/o CNS meta @2yr
98%
85%
0.18 (0.10-0.33)
(all grades, %)
OSIM
PLB
p
Diarrhea
46
20
NA
Paronychia
25
1
NA
Dry skin
23
6
NA
Pruritus
19
9
NA
Cough
18
17
NA
Stomatitis
18
4
NA
Nasopharyngitis
14
10
NA
Upper respiratory tract infection
13
10
NA
Decreased appetite
13
4
NA
Mouth ulceration
12
2
NA
Dermatitis acneiform
11
5
NA
  • Inclusion
  • Exclusion

- Male or female, aged at least 18 years. - Histologically confirmed diagnosis of primary non small lung cancer (NSCLC) on predominantly non-squamous histology - MRI or CT scan of the brain must be done prior to surgery as it is considered standard of care. - Patients must be classified post-operatively as Stage IB, II or IIIA on the basis of pathologic criteria. - Confirmation by the central laboratory that the tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations including T790M. - Complete surgical resection of the primary NSCLC is mandatory. All gross disease must have been removed at the end of surgery. All surgical margins of resection must be negative for tumour. - Complete recovery from surgery and standard post-operative therapy (if applicable) at the time of randomization. - World Health Organization Performance Status of 0 to 1 - Female patients should be using adequate contraceptive measures, should not be breast feeding, and must have a negative pregnancy test prior to first dose of study drug; or female patients must have an evidence of non-child-bearing potential.

Treatment with any of the following: - Pre-operative or post-operative or planned radiation therapy for the current lung cancer - Pre-operative (neo-adjuvant) platinum based or other chemotherapy - Any prior anticancer therapy - Prior treatment with neoadjuvant or adjuvant EGFR-TKI at any time - Major surgery (including primary tumour surgery, excluding placement of vascular access) within 4 weeks of the first dose of study drug - Patients currently receiving medications or herbal supplements known to be potent inducers of cytochrome P450 (CYP) 3A4 - Treatment with an investigational drug within five half-lives of the compound or any of its related material. - Patients who have had only segmentectomies or wedge resections - History of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer, or other solid tumours curatively treated with no evidence of disease for > 5 years following the end of treatment. - Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy. - Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). - Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of AZD9291. Any of the following cardiac criteria: • Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs, using the screening clinic ECG machine-derived QTc value. • Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG. • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval. - Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD. - Inadequate bone marrow reserve or organ function.

Characteristics
OSIM
PLB
Agedc-comma sex
Median age (range) yr
64 (30-86)
62 (31-82)
Male
32%
28%
Female
68%
72%
Smoking history
Yes
32%
25%
No
68%
75%
Smoking status
Former
31%
24%
Never
68%
75%
Current
1%
1%
Race
Asian
64%
64%
Non-Asian
36%
36%
WHO performance status
0
64%
64%
1
36%
36%
AJCC stage
IB
32%
32%
II
34%
34%
IIIA
35%
34%
Histologic type
Adenocarcinoma
96%
97%
Non-adenocarcinoma
4%
3%
Histologic subtype
Acinar adenocarcinoma
25%
24%
Malignant papillary adenocarcinoma
13%
13%
Malignant adenocarcinoma
54%
55%
Bronchioloalveolar adenocarcinoma
3%
4%
Histologic subtype
Solid adenocarcinoma with mucus formation
1%
1%
Bronchial gland carcinoma (not otherwise specified)
<1%
1%
Malignant adenosquamous carcinoma
1%
1%
Other
2%
1%
Lung cancer resection type
Lobectomy
97%
94%
Sleeve resection
<1%
1%
Bilobectomy
2%
2%
Pneumonectomy
1%
3%
Regional lymph nodes
N0
41%
42%
N1
29%
28%
N2
31%
30%
EGFR mutation type at randomization
Ex19del
55%
55%
L858R
45%
45%
p.Thr790Met
1%
1%
Adjuvant chemotherapy
Yes
60%
60%
No
40%
40%
Ad-hoc:
no.pts inv.
no.pts comp.
OSIM
PLB
HR
p
Total disease recurrence
339
343
11%
46%
Total CNS disease recurrence
339
343
2%
11%
  • DFS II-IIIA @2yr
analisys of DFS II-IIIA @2yr
OSIM
PLB
HR (95% CI)
Age (n)
<65 yr (380)
0.16 (0.09–0.26)
≥65 yr (302)
0.22 (0.13–0.36)
Sex (n)
Male (204)
0.19 (0.10–0.33)
Female (478)
0.18 (0.11–0.28)
Smoking history (n)
Yes (194)
0.10 (0.04–0.22)
No (488)
0.23 (0.15–0.34)
Stage (n)
IB (212)
0.39 (0.18–0.76)
II (236)
0.17 (0.08–0.31)
Stage (n)
IIIA (234)
0.12 (0.07–0.20)
EGFR mutation (n)
Ex19del (378)
0.12 (0.07–0.20)
L858R (304)
0.31 (0.18–0.49)
Adjuvant chemotherapy (n)
Yes (410)
0.16 (0.10–0.26)
No (272)
0.23 (0.13–0.40)
analisys of
OSIM
PLB
HR (95% CI)