1236MO - A single-arm phase II study of gefitinib with concurrent thoracic radiotherapy in unresectable locally-advanced non-small cell lung cancer patients with EGFR mutation (West Japan Oncology Group 6911L)

Background

Epidermal growth factor receptor mutation (EGFR)-tyrosine kinase inhibitor plays a key role in EGFR-mutated, metastatic non-small cell lung cancer (NSCLC). However, it has not been explored whether EGFR-TKI plus concurrent thoracic radiotherapy may be effective in locally-advanced NSCLC patients with EGFR mutation.

Methods

Chemotherapy-naïve, locally-advanced NSCLC patients with EGFR mutation were enrolled. Patients were treated with gefitinib (250mg/day, p.o. for 2 years) plus concurrent thoracic radiotherapy (64Gy/32frs). Primary endpoint was progression-free survival (PFS) at 2 years. Secondary endpoints consisted of overall response rate (ORR), PFS, overall survival (OS) and safety. Based on the hypothesis that this treatment will improve PFS rate at 2 years from 20 to 40% (0.05 of one-sided α and 0.25 of β), 27 patients are required (Trial Identifier, UMIN000008366).

Results

Between Aug 2012 and Nov 2017, 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; c-stage IIIA/IIIB 14/13. PFS rate at 2 years by independent review was 29.6% (one-sided 95% confidence interval [CI]: 17.6%-). ORR was 81.5% (95%CI: 66.5% to not reached), median PFS was 28.6 months (95%CI: 12.0 to 24.5 months), and median OS was 61.1 months (95%CI: 38.1 months to not reached). Adverse events ≥Gr 3 were fatigue, skin reaction and appetite loss (3.7%, respectively). Pneumonitis was frequently observed, but all events were mild (Gr1 59.2% and Gr2 29.6%).

Conclusions

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

Clinical trial identification

Trial Identifier, UMIN000008366.

Editorial acknowledgement

Legal entity responsible for the study

West Japan Oncology Group.

Funding

Astrazeneca.

Disclosure

J. Shimizu: Honoraria (self): AstraZeneca K.K.; Honoraria (self): MSD; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): Taiho Pharmaceutical. H. Akamatsu: Honoraria (self): AstraZeneca K.K.; Honoraria (self): Boehringer Ingelheim,; Honoraria (self), Research grant/Funding (self): Chugai Pharmaceutical; Honoraria (self), Research grant/Funding (self): Eli Lilly; Honoraria (self), Research grant/Funding (self): MSD K.K.; Honoraria (self): Ono Pharmaceutical Co., Ltd.; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Novartis. H. Murakami: Honoraria (self), Research grant/Funding (self): AstraZeneca K.K.; Honoraria (self), Research grant/Funding (self): Chugai Pharmaceutical; Honoraria (self), Research grant/Funding (self): Eli Lilly; Honoraria (self), Research grant/Funding (self): Taiho Pharmaceutical; Honoraria (self), Research grant/Funding (self): Takeda; Research grant/Funding (self): AbbVie; Research grant/Funding (self): Daiichi Sankyo; Research grant/Funding (self): IQvia; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Bristol-Myers Squibb Japan; Honoraria (self): MSD. H. Harada: Honoraria (self): AstraZeneca K.K.; Honoraria (self): BrainLab; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): Merck Biopharma; Honoraria (self): Daiichi Sankyo. H. Hayashi: Honoraria (self), Research grant/Funding (self): AstraZeneca K.K.; Honoraria (self), Research grant/Funding (self): Boehringer Ingelheim,; Honoraria (self): Bristol-Myers Squibb Co., Ltd.; Honoraria (self): Chugai Pharmaceutical Co. Ltd.; Honoraria (self): Eli Lilly Japan K.K.; Honoraria (self): MSD K.K.; Honoraria (self), Research grant/Funding (self): Ono Pharmaceutical Co. Ltd.; Honoraria (self): Pfizer Japan Inc.; Honoraria (self): Shanghai Haihe Biopharm; Honoraria (self): Kyorin pharmaceutical co. ltd; Honoraria (self): Novartis Pharma K.K.; Honoraria (self): Taiho Pharmaceutical Co. Ltd. H. Daga: Honoraria (self), Research grant/Funding (self): AstraZeneca K.K.; Honoraria (self): Boehringer Ingelheim,; Honoraria (self), Research grant/Funding (self): Chugai Pharmaceutical; Honoraria (self), Research grant/Funding (self): Eli Lilly; Honoraria (self): MSD K.K.; Honoraria (self): Ono Pharmaceutical Co.,Ltd.; Honoraria (self): Taiho Pharmaceutical; Research grant/Funding (self): Pfizer. Y.H. Kim: Honoraria (self): AstraZeneca K.K.; Honoraria (self): Chugai Pharmaceutical; Honoraria (self), Research grant/Funding (self): Ono Pharmaceutical Co. Ltd.; Honoraria (self): Bristol-Myers Squibb Co. Ltd.; Honoraria (self): MSD K.K.; Honoraria (self), Research grant/Funding (self): Taiho Pharmaceutical Co. Ltd.; Honoraria (self): Pfizer. T. Kato: Honoraria (self), Research grant/Funding (self): AbbVie; Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self), Research grant/Funding (self): Boehringer Ingelheim; Honoraria (self), Research grant/Funding (self): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (self): Chugai Pharmaceutical; Honoraria (self), Research grant/Funding (self): Eli Lilly; Honoraria (self), Research grant/Funding (self): Merck Biopharma; Honoraria (self), Research grant/Funding (self): MSD; Honoraria (self), Research grant/Funding (self): Novartis; Honoraria (self), Research grant/Funding (self): Ono Pharmaceutical; Honoraria (self), Research grant/Funding (self): Pfizer; Honoraria (self), Research grant/Funding (self): Taiho Pharmaceutical; Research grant/Funding (self): Amgen; Research grant/Funding (self): Astellas; Research grant/Funding (self): Kyowa-Kirin; Research grant/Funding (self): KYORIN Pharmaceutical Co., Ltd.; Research grant/Funding (self): Regeneron; Honoraria (self): Daiichi Sankyo; Honoraria (self): Nippon Kayaku Co., Ltd.; Honoraria (self): F. Hoffmann-La Roche; Honoraria (self): Nitto Denko; Honoraria (self): Sumitomo Dainippon; Honoraria (self): Shionogi; Honoraria (self): Takeda. N. Yamamoto: Honoraria (self), Research grant/Funding (self): AstraZeneca K.K.; Honoraria (self), Research grant/Funding (self): Boehringer Ingelheim,; Honoraria (self), Research grant/Funding (self): Chugai Pharmaceutical; Honoraria (self), Research grant/Funding (self): Eli Lilly; Honoraria (self), Research grant/Funding (self): MSD K.K.; Honoraria (self): Novartis; Honoraria (self), Research grant/Funding (self): Ono Pharmaceutical; Honoraria (self), Research grant/Funding (self): Pfizer; Research grant/Funding (self): Astellas Pharma Inc; Research grant/Funding (self): Bristol-Myers Squibb Japan; Research grant/Funding (self): Daiichi Sankyo; Research grant/Funding (self): Takeda Pharmaceutical; Research grant/Funding (self): Taiho Pharmaceutical; Research grant/Funding (self): Terumo Corporation; Honoraria (self): Toppan Printing Co., Ltd. K. Nakagawa: Honoraria (self), Research grant/Funding (self): AstraZeneca K.K.; Honoraria (self): Nichi-Iko Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (self): Astellas Pharma Inc.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Takeda Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (self): MSD K.K.; Honoraria (self), Research grant/Funding (self): Taiho Pharmaceutical Co., Ltd.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Ono Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (self): Bristol-Myers Squibb Company; Honoraria (self), Research grant/Funding (self): Nippon Boehringer Ingelheim Co., Ltd.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Eli Lilly Japan K.K.; Honoraria (self), Research grant/Funding (self): Novartis Pharma K.K.; Honoraria (self): SymBio Pharmaceuticals Limited; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Pfizer Japan Inc.; Honoraria (self), Research grant/Funding (self): Chugai Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (self): Daiichi Sankyo Co., Ltd.; Honoraria (self), Advisory/Consultancy: KYORIN Pharmaceutical Co., Ltd.; Honoraria (self): Thermo Fisher Scientific K.K.; Honoraria (self): Roche Diagnostics K.K.; Honoraria (self): Nippon Kayaku Co., Ltd.; Honoraria (self), Research grant/Funding (self): Bayer Yakuhin, Ltd.; Honoraria (self), Research grant/Funding (self): Merck Biopharma Co., Ltd.; Honoraria (self), Research grant/Funding (self): AbbVie Inc.; Research grant/Funding (self): Kissei Pharmaceutical Co., Ltd.; Research grant/Funding (self): Kyowa Hakko Kirin Co., Ltd; Research grant/Funding (self): Merck Serono Co., Ltd; Research grant/Funding (self): Eisai Co., Ltd.; Research grant/Funding (self): SymBio Pharmaceuticals Limited; Research grant/Funding (self): Otsuka Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.