1634 - Phase III Study Comparing Second- and Third-Generation Regimens With Concurrent Thoracic Radiotherapy in Patients With Unresectable Stage III Non–Small-Cell Lung Cancer: 10-year follow-up of West Japan Thoracic Oncology Group WJTOG0105

Background

Third-generation regimens with chemoradiotherapy (CRT) has been established as one of a standard treatment for patients with unresectable stage III non-small cell lung cancer (NSCLC) after first results of the phase III WJTOG0105 trial. However, the long-term survival and cumulative incidences of toxicity associated with CRT remains unclear. We report survival and late toxicities with a follow-up period of 10 years.

Methods

Eligible patients were randomly assigned to A (control), four cycles of mitomycin (8 mg/m2 on day 1)/vindesine (3 mg/m2 on days 1, 8)/cisplatin (80 mg/m2 on day 1) plus thoracic radiotherapy (TRT) 60 Gy; B, weekly irinotecan (20 mg/m2)/carboplatin (area under the plasma concentration-time curve [AUC] 2) for 6 weeks plus TRT 60 Gy, followed by two courses of irinotecan (50 mg/m2 on days1, 8)/carboplatin (AUC 5 on day1); C, weekly paclitaxel (40mg/m2)/carboplatin (AUC 2) for 6 weeks plus TRT 60 Gy, followed by two courses of paclitaxel (200mg/m2 on day1)/carboplatin (AUC 5 on day 1). Kaplan-Meier survival curves and 5- and 10-year survival probabilities were calculated. Late toxicities were defined as occurring later than 90 days after CRT initiation.

Results

From September 2001 to September 2005, 440 patients (arm A, n = 146; arm B arm, n = 147; arm C, n = 147) were enrolled. In the arm A, B and arm C, median overall survival (OS) time was 20.5, 19.8 and 22.0 months, 5-year survival probability was 20.9%, 16.0% and 18.2%, and 10-year survival probability was 13.6%, 7.5% and 15.2%, respectively. There were no significant differences in OS among the treatment arms. The 10-year progression-free survival (PFS) probability was 8.5%, 6.5%, and 11.1% in arm A, B and C. %Grade 3/4 late toxicities were 3.4% (heart 0.7%, lung 2.7%) in arm A and only lung 3.4% in arm B and lung 4.1% in arm C. No additional cases of late toxicity (Grade 3/4) were seen since the initial report.

Conclusions

Arm C shows similar efficacy and toxicity profiles compared with arm A, even 10 years after starting treatment. However, 10-year PFS probability was only 11%, and thus new treatment strategies incorporating immunotherapy are required.

Clinical trial identification

UMIN000030811.

Editorial acknowledgement

Legal entity responsible for the study

West Japan Oncology Group.

Funding

Has not received any funding.

Disclosure

Y. Zenke: Honoraria (self): Boheniger Ingelheim; Honoraria (self): Chugai Pharma; Honoraria (self): AstraZeneca; Honoraria (self): Lilly; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): MSD Oncology; Research grant / Funding (institution): MSD. M. Tsuboi: Honoraria (self): AstraZeneca; Honoraria (self): Lilly; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Daiichi Sankyo; Honoraria (self): Chugai Pharma; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Teijin Pharma; Honoraria (self): Johnson and Johnson; Honoraria (self): Coviden; Honoraria (self): Novartis; Honoraria (self): MSD; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Bristol-Myers Squibb; Research grant / Funding (institution): Boehringer Ingelheim. M. Satouchi: Honoraria (self): AstraZeneca; Honoraria (self): MSD; Honoraria (self): Chugai Pharma; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Pfizer; Honoraria (self): Boheriner Ingelheim; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Novartis; Honoraria (self): Lilly; Research grant / Funding (institution): Chugai; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Ignyta. H. Daga: Honoraria (self): MSD; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Chugai; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Chugai. D. Fujimoto: Honoraria (self): AstraZeneca; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Chugai Pharama; Honoraria (self): MSD; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Lilly; Research grant / Funding (institution): AstraZeneca. M. Mori: Honoraria (self): AstraZeneca; Honoraria (self): Chugai Pharma; Honoraria (self): MSD; Honoraria (self): Ono Pheramceutical; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Lilly; Research grant / Funding (institution): Chugai Pharma. T. Hirashima: Honoraria (self): Ono pharmaceutical; Honoraria (self): MSD; Honoraria (self): AstraZeneca; Honoraria (self): Lilly; Honoraria (self): Chugai Pharma; Honoraria (self): Brisotol-Myers Squibb; Honoraria (self): Pfizer; Honoraria (self): Kyowa-Hakko-Kirin; Honoraria (self): Boehringer Ingelheim; Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): MSD; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Brisotol-Myers Squibb; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Taiho Pharmaceutical. N. Yamamoto: Honoraria (self): Bristol-Myers Squibb; Research grant / Funding (institution): Bristol-Myers Squibb. K. Nakagawa: Honoraria (self), Research Funding(instistution): Astellas Pharma Inc.; Honoraria (self), Research Funding(instistution): AstraZeneca K.K.; Honoraria (self), Research Funding(instistution): MSD K.K.; Honoraria (self), Research Funding(instistution): Ono Pharmaceutical Co.,Ltd.; Honoraria (self), Research Funding(instistution): Daiichi Sankyo Co., Ltd.; Honoraria (self), Research Funding(instistution): Taiho Pharmaceutical Co.,Ltd.; Honoraria (self), Research Funding(instistution): Bristol-Myers Squibb Company; Honoraria (self): KYORIN Pharmaceutical Co.,Ltd.; Honoraria (self): Nichi-Iko Pharmaceutical Co., Ltd.; Honoraria (self): Hisamitsu Pharmaceutical Co.,Inc.; Honoraria (self), Research Funding(instistution): Takeda Pharmaceutical Co.,Ltd.; Honoraria (self), Research Funding(instistution): Chugai Pharmaceutical Co.,Ltd.; Honoraria (self), Research Funding(instistution): Eli Lilly Japan K.K.; Honoraria (self): Nippon Boehringer Ingelheim Co.,Ltd.; Honoraria (self), Research Funding(instistution): Novartis Pharma K.K.; Honoraria (self), Research Funding(instistution): Pfizer Japan Inc.; Honoraria (self): Thermo Fisher Scientific K.K.; Advisory / Consultancy, Research Funding(instistution): Astellas Pharma Inc.; Advisory / Consultancy: Takeda Pharmaceutical Co.,Ltd.; Research grant / Funding (institution): Merck Serono Co., Ltd. All other authors have declared no conflicts of interest.