363P- A multicenter, real-world observational study of efficacy and safety of first-line osimertinib treatment in patients withepidermal growth factor receptor (EGFR) activating mutation-positive advanced non-small cell lung cancer (Reiwa study)
Tomoya Fukui 1), 2), Katsuhiko Naoki 1), Kiyotaka Yoh 3), Kazuhiro Usui 4), Yukio Hosomi 5), Kazuma Kishi 6), Go Naka 7), Kageaki Watanabe 5), Kohei Uemura 8), Hideo Kunitoh 9)1) Department of Respiratory Medicine, Kitasato University School of Medicine, 2) Department of Respiratory Medicine, Shonan Kamakura General Hospital, 3) Department of Thoracic Oncology, National Cancer Center Hospital East,
4) Department of Respiratory Medicine, NTT Medical Center Tokyo, 5) Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital,
6) Department of Respiratory Medicine, Toho University Omori Medical Center, 7) Department of Respiratory Medicine, National Center for Global Health and Medicine,8) Department of Biostatistics and Bioinformatics, The Interfaculty Initiative in Information Studies, The University of Tokyo, 9) Department of Chemotherapy, Japan Red Cross Medical Center, Japan.

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Methods【Design】⚫ A multicenter, prospective cohort study in Japan【Patients】⚫ EGFR mutation-positive⚫ Advanced or recurrent NSCLC patients⚫ Started EGFR-TKI treatment from
September 2018 to August 2020 were enrolled⚫ Those receiving first-line osimertinib monotherapy
were followed-up for clinical courses.
【Primary endpoint】⚫ Progression free survival (PFS) with osimertinib
EGFR mutation-positive NSCLC
From Sep 2018 to Aug 2020
Obtained consent (n=660)
Ineligible (n=1)
Osimertinib(n=583)
A survey was
conducted once everysix months

Other EGFR-TKI(n=76)
Follow-up period
median 24.6 months(range, 0.1-42.0)

Correspondence to:
Tomoya Fukui, E-mail: tofukui@med.kitasato-u.ac.jp

Age, years
median (range)
Gendermalefemale
ECOG PS01
2
3
4
missing

72 (30-95)

224 (38.4)
359 (61.6)

216 (37.1)
281 (48.2)
60 (10.3)
20 (3.4)
2 (0.3)4 (0.7)

Ex19del, 23.5 m (20.9-27.4)
L858R, 17.0 m (15.2-19.7)

Probability of PFS⚫

All, 20.0 m (95%CI, 17.6-21.7)

n (%)

Probability of PFS⚫

Osimertinib is a third-generation, irreversible
EGFR-TKI that selectively inhibits both EGFRTKI-sensitizing and EGFR-T790M (resistant)mutations.
In a phase III trial (FLAURA), osimertinib showed
efficacy superior to that of first-generation
gefitinib and erlotinib, with a similar safety profileand lower rates of serious adverse events.
Osimertinib is currently being used as the firstline treatment for patients with advanced EGFR
mutation-positive NSCLC.
However, the efficacy and safety of osimertinib
treatment in real-world clinical practice have notbeen fully verified.

Adverse events

Survival by ECOG PS

Survival by mutation typePS0-1, 20.2 m (19.0-22.4)
PS2-4, 13.8 m (9.0-20.0)

Pneumonitis,n (%)

PS 0-1

Any grade67 (13.4)

8 (9.3)

Grade 119 (3.8)

2 (2.3)

Grade 234 (6.8)

2 (2.3)

Grade 310 (2.0)

2 (2.3)

Grade 44 (0.8)2 (2.3)

Grade 500

Smoking statusneverformer
current
Histology
adenosquamous
NOS
LCNEC
Mutation type*Ex19delL858R
others325 (55.8)
224 (38.4)
34 (5.8)571 (97.9)
9 (1.5)2 (0.3)1 (0.1)

Ex19del, not reached (40.9-NA)
L858R, 36.1 m (29.9-NA)

285 (48.9)
266 (45.6)
33 (5.7)

Brain metastases
yesno169 (29.0)
414 (71.0)

PS0-1, not reached (39.8-NA)
PS2-4, 18.8 m (14.0-31.8)

Exacerbation patternn (%)

9 (1.5)384 (65.9)
190 (32.6)

Flare(-),
379 (96.4%)

Flare defined as rapid disease deterioration within
one month resulting in hospitalization or death, after
discontinuation of osimertinib treatment, except in caseof causes not directly related to NSCLC exacerbation*One patient had both Ex19del and L858R mutations

Stage
locally advanced
metastaticrecurrence

PS 2-4

Disease flare
Flare(+), 14 (3.6%)

All, 40.9 m (95%CI, 36.3-NA)

Probability of OS⚫

Patient Characteristics (n=583)

Probability of OS

Background

CNS metastasis

Asymptomatic andno clinical exacerbation

Symptomatic andno clinical exacerbation

Clinical
exacerbation

total

15 (4.8)

4 (1.3)17 (5.4)

36 (11.4)

Single organ other than CNS (up to 3 per organ)

94 (30.0)28 (8.9)

16 (5.1)

138 (43.7)

Multiple organs

66 (20.9)

37 (11.7)

39 (12.3)

142 (44.9)

175 (55.4)

69 (21.8)

72 (22.8)316 (100)

Funding: This study is financially supported by AstraZeneca. AstraZeneca is not directly involved in the data management, source data verification, or the statistical analysis.
COI: TF, KN, KY, KU, YH, KK, GN, KW and HK have received personal fees from AstraZeneca; KN and KY have received research grants from AstraZeneca, outside the submitted work.

PS 0-1

PS 2-4All events

105 (21.3)

27 (31.4)

Pneumonitis

14 (2.8)

4 (4.7)Rash

14 (2.8)

3 (3.5)

AST/ALT increased

10 (2.0)

3 (3.5)

Neutropenia

9 (1.8)1 (1.2)

Paronychia

9 (1.8)0 (0)Anorexia

8 (1.6)3 (3.5)

Anemia7 (1.4)3 (3.5)

Diarrhea

4 (0.8)2 (2.3)

Thrombocytopenia

4 (0.8)1 (1.2)

Leukopenia

3 (0.6)

1 (1.2)

Prolonged QT interval

2 (0.4)2 (2.3)AE leading todiscontinuation, n (%)

PS 0-1

PS 2-4All events95 (19.1)

21 (24.4)

Pneumonitis

48 (9.7)

5 (5.8)

Hematotoxicity

6 (1.2)

1 (1.2)Rash

6 (1.2)5 (5.8)

Paronychia

6 (1.2)0 (0)AST/ALT increased

3 (0.6)2 (2.3)

Prolonged QT interval

1 (0.2)2 (2.3)Conclusion
⚫

Total

AE ≧ Grade 3, n (%)⚫
⚫

Osimertinib showed activity with a manageable safety
profile in clinical practice, consist with results ofprevious clinical trials.
Efficacy was different according to mutation type.
More evidence is needed for patients with poor PS.