A multicenter, real-world observational study of efficacy and safety of first-line
osimertinib treatment in patients with epidermal growth factor receptor (EGFR)
activating mutation-positive advanced non-small cell lung cancer (Reiwa study)
Susumu Takeuchi1), Norihiko Ikeda1), Kiyotaka Yoh2), Kazuhiro Usui3), Yukio Hosomi4),
Kazuma Kishi5), Go Naka6), Kageaki Watanabe4), Kohei Uemura7), Hideo Kunitoh8)
1) Department of Surgery, Tokyo Medical University, Shinjuku, Tokyo 160-0023, Japan.
2) Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba 277-8577, Japan.
3) Department of Respiratory Medicine, NTT Medical Center Tokyo, Shinagawa, Tokyo 141-0022, Japan.
4) Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo,Tokyo 113-8677, Japan.
5) Department of Respiratory Medicine, Toho University Omori Medical Center, Ota, Tokyo 143-8541, Japan.
6) Department of Respiratory Medicine, National Center for Global Health and Medicine, Shinjuku, Tokyo 162-8655, Japan.
7) Department of Biostatistics and Bioinformatics, The Interfaculty Initiative in Information Studies, The University of Tokyo, Bunkyo, Tokyo 113-8655, Japan.
8) Department of Chemotherapy, Japan Red Cross Medical Center, Shibuya, Tokyo 150-8935, Japan.

This study was coordinated by Public Health Research Foundation with funding from AstraZeneca.

Conflict of Interest disclosure slide for representative speakers or investigators
Research fund■scientific research fund □contract□other （） □N/A

Name oflead presenter

Susumu Takeuchi□donation

SponsorInstitution orcompany/position

employee or adviser of company and/or profit-making organizationNo■profit of stock■

patent fee■

lecturer fee□

manuscript fee■

research expenses from company■

contributions or endowed chair■fees of testimony, judgment, comment, etc.

■

presents or other payment■

representative of organization for clinical study receiving research expenses
from company■

Name of principal
investigatorNo
employee or adviser of company and/or profit-making organization■

profit of stock■

patent fee
manuscript fee■□■

research expenses from company■

contributions or endowed chair■fees of testimony, judgment, comment, etc.

■

presents or other payment■

representative of organization for clinical study receiving research expenses
from company■Tokyo Medical University

If yes, please specify the name of company, organization, your status.

AstraZeneca, Taiho, Ono, Nippon Kayaku, Kyowa Kirin, Eli Lilly and Company Japan, Bristol Myers
Squibb, Novartis Japan, MSD and Chugai Pharmaceutical Company Ltd.

Institution orcompany/position

Hideo Kunitohlecturer fee

This study was coordinated by Public Health Research
Foundation with funding from AstraZeneca.

Japanese Red Cross Medical CenterIf yes, please specify the name of company, organization, your status.

AstraZeneca, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Johnson and Johnson

Background⚫ Osimertinib is a third-generation, irreversible epidermal growth
factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) that
selectively inhibits both EGFR-TKI-sensitizing and EGFR-T790Mresistant mutations.
⚫ In a phase III FLAURA trial for untreated EGFR-mutated advanced
non-small cell lung cancer (NSCLC), osimertinib showed efficacy
superior to that of first-generation gefitinib and erlotinib, with asimilar safety profile and lower rates of serious adverse events.

Background⚫ Osimertinib is currently being used as the first-line
treatment for patients with advanced EGFR mutationpositive NSCLC.
⚫ However, the efficacy and safety of osimertinib treatment
in clinical practice have not been fully verified.

Objectives

We performed a multicentre, prospective cohort
study to evaluate the activity of osimertinib treatment
in clinical practice.

Inclusion Criteria⚫ EGFR mutation-positive⚫ Advanced or recurrent NSCLC patients⚫ Those receiving first-line osimertinib monotherapy
were followed-up for clinical courses.
Primary Endpoint
・Progression free survival (PFS) withosimertinib
Secondary Endpoint
・Overall survival (OS)・Objective Response Rate (ORR)
・Adverse events

Patient Flow Chart
EGFR mutation-positive NSCLC
From Sep 2018 to Aug 2020

Obtained consent (n=660)※Ineligible (n=1)

Osimertinib(n=583)A survey wasconducted once
every 6 months

Other EGFR-TKI(n=76)

Patient Characteristics (n=583)n (%)
Age, years
median (range)
Gendermalefemale
ECOG PS01
2
3
4
missing
Smoking statusneverformer
current
Histology
adenosquamousNOS
LCNEC

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)325 (55.8)
224 (38.4)
34 (5.8)571 (97.9)
9 (1.5)2 (0.3)1 (0.1)n (%)
Mutation type*Ex19delL858R
others285 (48.9)
266 (45.6)
33 (5.5)

Stage
locally advanced
metastatic
recurrence

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

Brain metastases
yesno169 (29.0)
414 (71.0)*One patient had both Ex19del and L858R mutations

PFS and OS by EGFR mutation type
PFSOS

All, 20.0 M (95%CI, 17.6-21.7)
ー Ex19del, 23.5 M (20.9-27.4)
ー L858R, 17.0 M (15.2-19.7)

delAll, 40.9 M (95%CI, 36.3-NA)
ー Ex19del, not reached (40.9-NA)
ー L858R, 36.1 M (29.9-NA)

delPFS and OS by ECOG PS
PFS

ー PS0-1, 20.2 M (19.0-22.4)
ー PS2-4, 13.8 M (9.0-20.0)

OSー PS0-1, not reached (39.8-NA)
ー PS2-4, 18.8 M (14.0-31.8)

Objective Response Rate (ORR)

Overall response rate：68% (95%CI, 63.8-71.5)
Disease control rate：87% (95%CI, 83.7-89.4)
Response to the therapyn (%)

Complete response (CR)

17 (2.9)

Partial response (PR)378 (64.8)

Stable Disease (SD)111 (19.1)

Progressive disease (PD)46 (7.9)

Not evaluable (NE)

28 (4.8)

Exacerbation patternn (%)

Asymptomatic andno clinicalexacerbation

Symptomatic andno clinicalexacerbation

Clinical
exacerbation

Total

CNS-only
metastasis

15 (4.8)

4 (1.3)17 (5.4)

36 (11.4)

Single organ
other than CNS(up to 3 lesions)

94 (29.7)

28 (8.9)

16 (5.1)

138 (43.7)

Multiple organs

66 (20.9)

37 (11.7)

39 (12.3)

142 (44.9)

Total

175 (55.4)

69 (21.8)

72 (22.8)316 (100)

Adverse events

Adverse events leading to discontinuation
AE leading todiscontinuation, n (%)

Total

PS 0-1

PS 2-4All events

116 (20.0)

95 (19.1)

21 (24.4)

Pneumonitis

53 (9.1)

48 (9.7)

5 (5.8)

Hematological toxicity

7 (1.2)6 (1.2)

1 (1.2)Rash

11 (1.9)

6 (1.2)5 (5.8)

Paronychia

16 (1.0)

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

5 (0.9)3 (0.6)2 (2.3)

Prolonged QT interval3 (0.5)

1 (0.2)2 (2.3)

Pneumonitis
n (%)

Total

PS 0-1

PS 2-4

All grade75 (12.9)

67 (13.4)

8 (9.3)

Grade 121 (3.6)

19 (3.8)

2 (2.3)

Grade 236 (6.2)

34 (6.8)

2 (2.3)

Grade 3

12 (2)

10 (2.0)

2 (2.3)

Grade 46 (1.0)4 (0.8)2 (2.3)

Grade 5000

Conclusion

This study reproduced the efficacy and safety results ofosimertinib in FLAURA trial in real-world Japanese patients.

List of Investigator Sites
KKR Sapporo Medical Center

Kyorin University HospitalFujisawa City Hospital

Hokkaido University Hospital

Japanese Red Cross Medical Center

Kanagawa Cancer Center

Iwate Prefectural Central Hospital

National Center for Global Health andMedicine

Showa University Northern Yokohama
Hospital

Tohoku University Hospital

Showa University Hospital

Niigata Cancer Center Hospital

Japanese Red Cross Akita HospitalTokyo Medical University Hospital

Kanazawa University Hospital

Ibaraki Prefectural Central HospitalTokyo Saiseikai Central Hospita

Shinshu University Hospital

Gunma University Hospital

Toho University Omori Medical Center

Hamamatsu University Hospital

Kasukabe Medical center

Mitsui Memorial Hospital

National Cancer Center Hospital East

Juntendo University Hospital

NTT Medical Center Tokyo

Tokyo Metropolitan Police Hospital

Okayama University HospitalTokyo Metropolitan Cancer and Infectious
Diseases Center Komagome Hospital

Kitasato University Hospital

Ehime University Hospital

Yokohama Municipal Citizen's Hospital

Okinawa National Hospital

Osaka Medical and Pharmaceutical
University Hospital
Hyogo Prefectural Amagasaki General
Medical Center