NSCLC: FLAURA trial

Abbreviations

No EU-CTR

  • FLAURA references
    2020-01-02
    S.S. Ramalingam
    Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC
    2018-01-11
    J.-C. Soria
    Osimertinib in Untreated EGFR-Mutated Advanced Non–Small-Cell Lung Cancer
Investigated (inv)
Comparator (comp)

OSIM

erlo or gefi

279

277

Phase:

3

Randomisation:

Double blind

Primary tumour:

NSCLC

Subtype (biomarker):

EGFR MT

Stage:

meta

Line of therapy:

L1

Primary
OSIM
erlo or gefi
HR
p
PFS
18.9 mo
10.2 mo
0.46 (0.37-0.57)
<0.001
OS
38.6 mo
31.8 mo
0.80 (0.64-1.00)
0.046
Secondaries
OSIM
erlo or gefi
HR
p
OS
38.6 mo
31.8 mo
0.80 (0.64-1.00)
0.046
ORR
80%
76%
0.24
DoR
17.2 mo
8.5 mo
(all grades, %)
OSIM
erlo or gefi
p
Any AE gr. ≥3
34
45
NA
Rash or acne
59
79
NA
Diarrhea
60
58
NA
Paronychia
35
33
NA
Stomatitis
29
22
NA
Anemia
16
10
NA
Upper respiratory tract infection
13
10
NA
Prolonged QT interval on ECG
10
4
NA
AST increased
10
25
NA
ALT increased
7
27
NA
Vomiting
15
12
Nasopharyngitis
11
6
Musculoskeletal pain
10
5
Alopecia
8
13
  • Inclusion
  • Exclusion

- Male or female, aged at least 18 years. - Pathologically confirmed adenocarcinoma of the lung. - Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy. - The tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R). - Mandatory provision of an unstained, archived tumour tissue sample in a quantity sufficient to allow for central analysis of EGFR mutation status. - Patients must be treatment-naïve for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with gefitinib or erlotinib as selected by the participating centre. Prior adjuvant and neo-adjuvant therapy is permitted (chemotherapy, radiotherapy, investigational agents). - Provision of informed consent prior to any study specific procedures, sampling, and analysis. - World Health Organization Performance Status of 0 to 1 with no clinically significant deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks.

Treatment with any of the following: - Prior treatment with any systemic anti-cancer therapy for locally advanced/metastatic NSCLC. - Prior treatment with an EGFR-TKI. - Major surgery within 4 weeks of the first dose of study drug. - Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation 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. - Alternative anti-cancer treatment - Treatment with an investigational drug within five half-lives of the compound or any of its related material. - Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of study drug. - Spinal cord compression, symptomatic and unstable brain metastases, except for those patients who have completed definitive therapy, are not on steroids, have a stable neurologic status for at least 2 weeks after completion of the definitive therapy and steroids. - 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 QTcF value. • Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG. • Any patient with 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. - Involvement in the planning and/or conduct of the study.

Characteristics
OSIM
erlo or gefi
Agedc-comma sex
Median age (range) yr
64 (26-85)
64 (35-93)
Male - no.(%)
101 (36)
105 (38)
Race - no.(%)
White
101 (36)
100 (36)
Asian
174 (62)
173 (62)
Other
4 (1)
4 (1)
Smoking status - no.(%)
Never
182 (65)
175 (63)
Current
8 (3)
9 (3)
Former
89 (32)
93 (34)
WHO performance status - no.(%)
0
112 (40)
116 (42)
1
167 (60)
160 (58)
Missing data
0
1 (<1)
Histologic type - no.(%)
Adenocarcinoma
275 (99)
272 (98)
Other
4 (1)
5 (2)
Overall disease classification - no.(%)
Metastatic
264 (95)
262 (95)
Locally advanced
14 (5)
15 (5)
Missing data
1 (<1)
0
Metastases - no.(%)
Visceral metastases
94 (34)
103 (37)
CNS metastases
53 (19)
63 (23)
EGFR mutation type at randomizat
Exon 19 deletion
175 (63)
174 (63)
L858R
104 (37)
103 (37)
EGFR mutation type by central te
Exon 19 deletion
158 (57)
155 (56)
L858R
97 (35)
90 (32)
No mutationdc-comma invalid testdc-comma or inadequate sample
24 (9)
32 (12)
EGFR-TKI comparator - no.(%)
Gefitinib (gefi)
183 (66)
Erlotinib (erlo)
94 (34)
Ad-hoc:
no.pts inv.
no.pts comp.
OSIM
erlo or gefi
HR
p
PFS in CNS metastases pts
53
63
15.2 mo
9.6 mo
0.47 (0.30-0.74)
<0.001
PFS in w/o CNS metastases pts
226
214
19.1 mo
10.9 mo
0.46 (0.36-0.59)
<0.001
  • PFS
  • OS
analisys of PFS
OSIM
erlo or gefi
HR (95% CI)
Sex (n)
Male (206)
0.58 (0.41–0.82)
Female (350)
0.40 (0.30–0.52)
Age (n)
<65 yr (298)
0.44 (0.33–0.58)
≥65 yr (258)
0.49 (0.35–0.67)
Known or treated CNS metastases at trial entry (n)
Yes (116)
0.47 (0.30–0.74)
No (440)
0.46 (0.36–0.59)
WHO performance status (n)
0 (228)
0.39 (0.27–0.56)
1 (327)
0.50 (0.38–0.66)
EGFR mutation at randomization (n)
Exon 19 deletion (349)
0.43 (0.32–0.56)
L858R (207)
0.51 (0.36–0.71)
EGFR mutation by circulating tumor DNA (n)
Positive (359)
0.44 (0.34–0.57)
Negative (124)
0.48 (0.28–0.80)
Centrally confirmed EGFR mutation (n)
Positive (500)
0.43 (0.34–0.54)
Negative (6)
NC
Smoking history (n)
Yes (199)
0.48 (0.34–0.68)
No (357)
0.45 (0.34–0.59)
Race (n)
Asian (347)
0.55 (0.42–0.72)
Non-Asian (209)
0.34 (0.23–0.48)
analisys of OS
OSIM
erlo or gefi
HR (95% CI)
Age
<65 yr
0.72 (0.54–0.97)
≥65 yr
0.87 (0.63–1.22)
Sex
Male
0.79 (0.55–1.14)
Female
0.79 (0.60–1.04)
Smoking history
Yes
0.70 (0.49–1.00)
No
0.85 (0.64–1.12)
CNS metastases at trial entry
Yes
0.83 (0.53–1.30)
No
0.79 (0.61–1.01)
WHO performance status
0
0.93 (0.63–1.37)
1
0.70 (0.54–0.91)
EGFR mutation at randomization
Exon 19 deletion
0.68 (0.51–0.90)
L858R
1.00 (0.71–1.40)
EGFR mutation detected by DNA in blood
Positive
0.77 (0.60–0.99)
Negative
0.72 (0.37–1.36)
Centrally confirmed EGFR mutation
Positive
0.75 (0.60–0.95)
Negative
NC
Race
Asian
1.00 (0.75–1.32)
Non-Asian
0.54 (0.38–0.77)