Weekly Cisplatin Plus Radiation for Postoperative Head and Neck Cancer (JCOG1008): A Multicenter, Noninferiority, Phase II/III Randomized Controlled Trial.

Purpose: The standard treatment for postoperative high-risk locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) is chemoradiotherapy with 3-weekly cisplatin (100 mg/m ² ). However, whether chemoradiotherapy with weekly cisplatin (40 mg/m ² ) yields comparable efficacy with 3-weekly cisplatin in postoperative high-risk LA-SCCHN is unknown.
Patients and Methods: In this multi-institutional open-label phase II/III trial, patients with postoperative high-risk LA-SCCHN were randomly assigned to receive either chemoradiotherapy with 3-weekly cisplatin (100 mg/m ² ) or with weekly cisplatin (40 mg/m ² ) to confirm the noninferiority of weekly cisplatin. The primary end point of phase II was the proportion of treatment completion, and that of phase III was overall survival. A noninferiority margin of hazard ratio was set at 1.32.
Results: Between October 2012 and December 2018, a total of 261 patients were enrolled (3-weekly cisplatin, 132 patients; weekly cisplatin, 129 patients). At the planned third interim analysis in the phase III part, after a median follow-up of 2.2 (interquartile range 1.19-3.56) years, chemoradiotherapy with weekly cisplatin was noninferior to 3-weekly cisplatin in terms of overall survival, with a hazard ratio of 0.69 (99.1% CI, 0.374 to 1.273 [< 1.32], one-sided P for noninferiority = .0027 < .0043). Grade 3 or more neutropenia and infection were less frequent in the weekly arm (3-weekly v weekly, 49% v 35% and 12% v 7%, respectively), as were renal impairment and hearing impairment. No treatment-related death was reported in the 3-weekly arm, and two (1.6%) in the weekly arm.
Conclusion: Chemoradiotherapy with weekly cisplatin is noninferior to 3-weekly cisplatin for patients with postoperative high-risk LA-SCCHN. These findings suggest that chemoradiotherapy with weekly cisplatin can be a possible treatment option for these patients.
Competing Interests: Naomi KiyotaHonoraria: Ono Pharmaceutical, Bristol Myers Squibb Japan, Bayer, Chugai Pharma, Merck Serono, MSD, Eisai, AstraZenecaConsulting or Advisory Role: Shift Zero, Ono Pharmaceutical, Ascent Development ServicesSpeakers' Bureau: Ono Pharmaceutical, Bristol Myers Squibb Japan, Merck Serono, Eisai, Bayer, MSD, Chugai PharmaResearch Funding: Ono Pharmaceutical (Inst), Bristol Myers Squibb (Inst), Pfizer (Inst), Roche (Inst), Rakuten Medical (Inst), Adlai Nortye (Inst) Makoto TaharaHonoraria: Merck Serono, Bristol Myers Squibb, Eisai, Ono Pharmaceutical, MSDConsulting or Advisory Role: Ono Pharmaceutical, MSD, Pfizer, Bristol Myers Squibb, Rakuten Medical, Bayer, LillyResearch Funding: Merck Sharp & Dohme (Inst), AstraZeneca (Inst), Ono Pharmaceutical (Inst), Novartis (Inst), Pfizer (Inst), Bristol Myers Squibb (Inst), Rakuten Medical (Inst), Bayer (Inst), GlaxoSmithKline (Inst), Lilly (Inst) Junki MizusawaHonoraria: Chugai Pharma, Taiho Pharmaceutical Takeshi KodairaConsulting or Advisory Role: Ono Pharmaceutical, Chugai PharmaSpeakers' Bureau: Merck Serono, Hitachi, Bristol Myers Squibb Japan, Accuray, Elekta, Ono Pharmaceutical, Canon USA, AstraZeneca, Chugai Pharma Nobuhiro HanaiHonoraria: Ono Pharmaceutical, Bristol Myers Squibb, Merck, MSD K.K, Eisai, Ethicon/Johnson & Johnson, AmcoConsulting or Advisory Role: SanwaResearch Funding: Ono Pharmaceutical, Chugai Pharma, Rakuten Medical, Bristol Myers Squibb/Ono Pharmaceutical, GlaxoSmithKline K.K, MSD K.K Hiroki HaraHonoraria: Chugai Pharma, Taiho Pharmaceutical, Merck Serono, Yakult Honsha, Lilly, Ono Pharmaceutical, Takeda, Bristol Myers Squibb, Sanofi, MSD, Daiichi Sankyo, Kyowa Hakko Kirin, BayerConsulting or Advisory Role: Ono Pharmaceutical, MSD, Lilly, Boehringer Ingelheim, Dainippon SumitomoResearch Funding: AstraZeneca (Inst), Chugai Pharma (Inst), Merck Serono (Inst), MSD (Inst), Ono Pharmaceutical (Inst), Taiho Pharmaceutical (Inst), Boehringer Ingelheim (Inst), Dainippon Sumitomo Pharma (Inst), Daiichi Sankyo (Inst), Pfizer (Inst), Eisai (Inst), Incyte (Inst), BeiGene (Inst), Astellas Pharma (Inst), Bayer (Inst), Elevar Therapeutics (Inst) Kaoru TanakaHonoraria: AstraZeneca, Merck Serono, Ono Pharmaceutical, Bristol Myers Squibb, Eisai, MSD, Kyowa Kirin Co, Ltd Akihiro HommaConsulting or Advisory Role: Rakuten Medical Japan, Olympus Medical SystemsSpeakers’ Bureau: Bristol Myers Squibb Japan, Mitsubishi Tanabe Pharma, Eisai, Makichie, Merck Serono, MSD K.K, Ono Pharmaceutical, Sanofi, Nobelpharma, BayerResearch Funding: Taiho Pharmaceutical (Inst), Kyorin Pharmaceutical (Inst), Otsuka Pharmaceutical Factory (Inst), Eisai (Inst) Nobuhiko OridateSpeakers' Bureau: Ono Pharmaceutical, Bristol Myers Squibb Japan, Merck Biopharma/Japan, Taiho Pharmaceutical, MSDResearch Funding: Ono Pharmaceutical, Merck biopharma/Japan, Taiho Pharmaceutical, Daiichi Sankyo Japan Tsutomu UedaHonoraria: Mitsubishi Tanabe Pharma, Bayer, Taiho Pharmaceutical, MSD, Ono PharmaceuticalResearch Funding: Ono Pharmaceutical Kenichi NakamuraHonoraria: Bayer Yakuhin, Chugai Pharma, Taiho PharmaceuticalResearch Funding: Astellas Pharma (Inst), Eisai (Inst), Otsuka (Inst), Ono Pharmaceutical (Inst), Kyorin (Inst), Daiichi Sankyo (Inst), Taiho Pharmaceutical (Inst), Takeda (Inst), Chugai/Roche (Inst), Novartis (Inst), Pfizer (Inst), Bayer (Inst), Bristol Myers Squibb Japan (Inst), Boehringer Ingelheim Seiyaku (Inst) Ryuichi HayashiConsulting or Advisory Role: Rakuten Medical JapanNo other potential conflicts of interest were reported.