JCOG1106 is a phase II trial to evaluate the efficacy and safety of chemoradiotherapy (CRT) with and without induction chemotherapy (CT) to determine which is more promising CRT regimen for LAPC. Primary endpoint was overall survival (OS). 102 patients (pts) were randomized to CRT (Arm A) or induction CT followed by CRT (Arm B), and 100 pts (Arm A/B n = 51/49) were eligible. In the primary analysis performed 1 year after completion of enrollment, 1-year OS for Arm A/B were reported to be 66.7/69.3% (hazard ratio [HR] 1.16), and Arm B was considered more promising based on pre-specified decision rule (J Clin Oncol 33, 2015, suppl; abst 4116). Although the probability of survival was greater in Arm B in the first 12 months, there was a possibility that it would be greater in Arm A in the following period. We performed final analysis 1 year after primary analysis.
Pts in Arm A received RT (50.4 Gy/28 fr) with concurrent S-1 (40 mg/m2/dose, b.i.d. on the day of irradiation). Pts in Arm B received induction gemcitabine (GEM) (1,000 mg/m2, iv, days 1, 8 and 15, every 4 weeks) for 12 weeks, and then, only pts with controlled disease received same CRT as Arm A. After CRT, GEM was continued until disease progression or unacceptable toxicity in both arms. Decision rule was set as follows: Arm B, which was expected to be less-toxic, will be considered more promising if point estimate of HR of OS for Arm B to Arm A is smaller than 1.186.
In the final analysis, 2-year OS for Arm A/B were 36.9/18.9% and HR was 1.26 [95%CI 0.82-1.93]. 2-year progression-free survival were 8.6/4.2% (HR 1.03), and 2-year distant metastasis-free survival were 14.8/4.2% (HR 1.20). Incidences of grade 3/4 toxicities in Arm A/B were leukopenia 62/61%, neutropenia 54/57%, anemia 18/12%, thrombocytopenia 10/14%, anorexia 16/4%, fatigue 8/4%, nausea 8/2%, diarrhea 6/4%, gastroduodenal (GD) hemorrhage 10/6%, GD ulcer 6/4%, and biliary infection 20/27%. Three treatment-related deaths occurred in Arm A (pneumonitis, GD hemorrhage, biliary infection).
Compared to CRT alone, CRT with Induction CT of gemcitabine resulted in a poorer long-time outcome, in spite of a favorable short-time outcome.
Clinical trial identification
Legal entity responsible for the study
Grants from MHLW, Japan. Grants from Japan AMED.
T. Ioka: Honoraria: Eisai, Nippon Kayaku, Taiho Pharmaceutical. Consultant: Taiho Pharmaceutical. Funding: Eisai, Taiho Pharmaceutical. Grants: MHLW, Japan, Japan AMED. A. Fukutomi: Honoraria: Eli Lilly, Taiho Pharmaceutical. Research funding: Taiho Pharmaceutical. Grants: MHLW, Japan. Grants: Japan AMED. J. Mizusawa, H. Katayama, S. Nakamura, Y. Ito, N. Hiraoka, K. Sugimori, K. Shimizu, M. Ozaka, H. Yanagimoto, T. Azuma, N. Sata: Grants: MHLW, Japan, Japan AMED. M. Ueno: Honoraria: Eli Lilly, Novartis, Taiho Pharmaceutical. Research funding: Eisai, Taiho Pharmaceutical. Grants: MHLW, Japan, Japan AMED. M. Ikeda: Honoraria: Taiho Pharmaceutical. Grants: MHLW, Japan, Japan AMED.
T. Okusaka: Research funding and Honoraria: Eli Lilly, Taiho Pharmaceutical. Grants: MHLW, Japan, Japan AMED. S. Nakamori: Research funding: Eizai. Grants: MHLW, Japan, Japan AMED. A. Hosokawa: Honoraria: Eisai, Taiho Pharmaceutical. Research funding: Taiho Pharmaceutical. Grants: MHLW, Japan, Japan AMED. T. Mine: Resarch funding: Eli Lily, Taiho Pamrmaceutical. Grants: MHLW, Japan, Japan AMED. J. Furuse: Personal financial interests: Eizai, Eli Lilly, Nippon Kayaku, Novartis, Pfizer, Sandoz, Taiho Pharmaceutical, Takeda Pharmaceutical. Institutional financial interests: Taiho Pharmaceutical. Grants; MHLW, Japan, Japan AMED.