851MO - Final analysis of a phase II/III trial of post-operative chemoradiotherapy comparing 3-weekly cisplatin with weekly cisplatin in high-risk patients with squamous cell carcinoma of the head and neck (JCOG1008)

Background

JCOG1008 was a multi-institutional randomized phase II/III trial which compared weekly cisplatin (CDDP)+RT (40 mg/m², qwk, 66 Gy/33Fr) with 3-weekly CDDP+RT (100 mg/m², q3wk, 66 Gy/33Fr) in post-operative high-risk squamous cell carcinoma of the head and neck (SCCHN). Interim analysis had demonstrated the non-inferiority of weekly CDDP+RT in overall survival (OS) with a better acute toxicity profile (J Clin Oncol. 2022;40(18):1980-1990). Here, we report the final analysis of JCOG1008.

Methods

The aim of the trial was to confirm the non-inferiority of weekly CDDP+RT (Arm B) to 3-weekly CDDP+RT (Arm A) in patients (pts) with post-operative high-risk SCCHN. Primary endpoint of phase III was OS, and secondary endpoints included relapse-free survival (RFS), local relapse-free survival (LRFS) and adverse events (AEs). A non-inferiority margin of hazard ratio (HR) was set at 1.32. The data used in this final analysis were obtained at 5 years after last patient enrollment.

Results

Between Oct 2012 and Dec 2018, 261 pts were enrolled (Arm A 132 pts, Arm B 129 pts). At final analysis with a median follow-up of 5.6 years, 5-year OS was 58.7% in Arm A and 71.2% in Arm B (HR 0.76, 95% CI, 0.52-1.12 [<1.32]), which maintained the non-inferiority of Arm B. 5-year RFS/LRFS was 53.0%/57.2% in Arm A and 64.3%/68.8% in Arm B (HR 0.81, [95% CI, 0.57-1.16]; HR 0.79, [95% CI, 0.54-1.14]), respectively. There were fewer deaths from any cause and cancer-specific deaths in Arm B (Arm A; 60/45 vs. Arm B; 48/32). Regarding disease events, local recurrence occurred in 21 pts in Arm A and 19 pts in Arm B; distant recurrence only occurred in 34 pts in Arm A and 24 pts in Arm B; and second primary disease occurred in 27 pts in Arm A and 31 pts in Arm B, the most common site of which was the esophagus. Regarding late AEs, any grade/grade 3 or more late AEs occurred in 91.5%/10.1% in Arm A and 94.2%/13.2% in Arm B.

Conclusions

At final analysis with 5-year follow up, the non-inferiority of weekly CDDP+RT was maintained. These results further support the use of weekly CDDP+RT as standard treatment.

Clinical trial identification

jRCTs031180135.

Editorial acknowledgement

Legal entity responsible for the study

Head and Neck Cancer Study Group of the Japan Clinical Oncology Group (JCOG-HNCSG).

Funding

The National Cancer Center Research and Development Funds and Japan Agency for Medical Research and Development (AMED).

Disclosure

M. Tahara: Financial Interests, Personal, Advisory Board: Merck Biopharma, Ono pharma, MSD, Pfizer, Bayer, Lilly, Rakuten Medical, Boehringer Ingelheim, AstraZeneca; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Eisai, Novartis; Financial Interests, Institutional, Local PI: MSD, AstraZeneca, Ono Pharma, Novartis, Pfizer, Bristol Myers Squibb, Loxo, GSK, Lilly, Rakuten Medical, Bayer, Merck Biophama; Financial Interests, Institutional, Research Grant: Bayer. N. Kiyota: Financial Interests, Personal, Invited Speaker: Ono pharmaceutical, Bristol Myers Squibb, Bayer, MSD, Eisai, Lilly, Novartis, Meck Biopharma; Financial Interests, Institutional, Local PI: Ono pharmaceutical, AstraZeneca, Rakuten Medical, Roche, Bayer, Boehringer Ingelheim, Lilly, Abbvie, GSK; Financial Interests, Institutional, Steering Committee Member: Adlai Nortye. N. Hanai: Financial Interests, Personal, Invited Speaker: Rakuten Medical K.K.; Financial Interests, Institutional, Local PI: MSD K.K, Adley Nortye. T. Fujii: Financial Interests, Personal, Invited Speaker: Merck Biopharma Co, Ltd, Taiho Phamaceutical Co, Ltd, Rakuten Medical, MSD, Medtronic. K. Tanaka: Financial Interests, Personal, Invited Speaker: AstraZeneca K.K, Merck Biopharma Co. Ltd, Eisai Co. Ltd, Bristol Myers Squibb Co. Ltd, Ono pharmaceutical Co. Ltd, MSD K.K, Chugai Pharmaceutical Co. Ltd, Takeda Pharmaceutical Co. Ltd, Taiho Pharmaceutical Co. Ltd, Novartis Pharma K.K, Kyowa Hakko Kirin Co. Ltd. T. Kodaira: Financial Interests, Personal, Invited Speaker: Merck Serono Co, Accuray Co, Ozuka Pharmaceutical Co, AstraZeneca Co, Jansen Pharmaceutical K.K, MSD co, Hitachi Co.; Financial Interests, Institutional, Advisory Board: Canon Co. J. Mizusawa: Financial Interests, Personal, Other, Honoraria: Chugai pharmaceutical, Taiho pharmaceutical; Other, My spouse receives salary: Pfizer. K. Nakamura: Financial Interests, Personal, Invited Speaker: Chugai, Taiho, AstraZeneca, Lilly, Takeda. R. Hayashi: Financial Interests, Institutional, Advisory Board: Rakuten Medical; Financial Interests, Coordinating PI: Shimadzu. All other authors have declared no conflicts of interest.