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A phase II study of gefitinib with concurrent thoracic radiotherapy in patients with unresectable, stage III Non-Small Cell Lung Cancer harboring EGFR mutations (A phase II study of gefitinib with concurrent thoracic radiotherapy in patients with unresectable, stage III Non-Small Cell Lung Cancer harboring EGFR mutations)

A phase II study of gefitinib with TRT in patients with stage III NSCLC harboring EGFR mutations (A phase II study of gefitinib with TRT in patients with stage III NSCLC harboring EGFR mutations)

28

A total of 28 patients were enrolled and 27 were eligible. Of those, median age was 67 (range, 45-74); male/female 7/20; never/current or former smoker 15/12; ECOG performance status 0/1 19/8; EGFR exon 19 deletion/exon 21 L858R 13/14; and c-stage IIIA/IIIB 14/13.

Between Aug 2012 and Nov 2017, 28 patients were enrolled and 27 were eligible and treated with the protocol therapy.

Pneumonitis was frequently observed, but all events were mild (Grade 1 59.2% and Grade 2 29.6%). Severe adverse events Grade 3-4 were increased ALT (59.3%), increased AST (37.0%), fatigue (3.7%), skin reaction (3.7%) and appetite loss (3.7%). Most of the severe adverse events was manageable liver dysfunction, and there was no treatment-related death.

In this study, we set PFS rate at two-years as the primary endpoint. For sample size calculation, we assumed an improvement of PFS rate at 2 years from 20% to 40%. As a result, PFS rate at 2 years by independent review was 29.6% (one-sided 95% confidence interval [CI]: 17.6%-), which did not meet the primary endpoint. ORR was 81.5% (95%CI: 63.3-91.3%). Median PFS was 18.6 months (95% CI: 12.0-24.5 months) and PFS rates at one-year was 66.7% (95% CI: 45.7-81.1%). Median OS was 61.1 months (95%CI: 38.1 months to not reached) and survival rate at one- and two-year was 100.0% and 96.3%, respectively.

Among unresectable locally-advanced NSCLC patients with EGFR mutation, gefitinib with concurrent thoracic radiotherapy showed manageable safety profiles, but did not improve PFS rate at 2 years.

Dec. 21, 2020

June. 09, 2021

https://www.sciencedirect.com/science/article/pii/S1556086421021900

No

Not applicable

https://jrct.mhlw.go.jp/latest-detail/jRCTs041180080

Murakami Haruyasu

Shizuoka Cancer Center

1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka

ha.murakami@scchr.jp

Murakami Haruyasu

Shizuoka Cancer Center

1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka

+81-55-989-5222

ha.murakami@scchr.jp

Complete

Aug. 21, 2012

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

prevention purpose

1) Pathologically confirmed NSCLC
2) Treatment naive unresectable stage III disease
3) Harboring EGFR mutation
4) Age of 20 to 75 years
5) ECOG PS of 0 or 1
6) Evaluable target lesions as per RECIST ver. 1.1
7) Adequate organ function
8) Confirmed as eligible for the protocol defined radiotherapy by radiologists
9) Written informed consent

1) Harboring exon 20 T790M mutation.
2) Incapable of oral intake
3) With intestinal paralysis, or ileus
4) Chronic diarrhea
5)Exhibiting significant interstitial pneumonitis, or pulmonary fibrosis in the chest CT
6) Active infection
7) Positive for HBs antigen
8) Uncontrolled diabetes mellitus
9) Severe heart disease
10) Systemic treatment with steroids
11) Concomitant cancers within 5 years
12) Prior history of thoracic radiotherapy
13) History of sereous drug allegies
14) Pregnancy, breast feeding, or hesitation in contraception
15) Other conditions not suitable for this study

Both

Non-Small Cell Lung Cancer

An oral dose of 250mg of gefitinib is administered daily beginning on day 1, with once-daily thoracic radiotherapy delivered at 2 Gy per day to a total dose of 64 Gy.

014

Progression free survival rate at 2 years.

Overall response rate, progression free survival rate at 1 year, progression free survival, survival rate at 1 year, survival rate at 2 years, overall survival, and safety.

+81-55-989-5222

Nov. 27, 2018

None