Long-Term Follow-Up of JCOG1008, a Randomized Phase II/III Trial of Chemoradiotherapy Comparing 3-Weekly Cisplatin With Weekly Cisplatin in Postoperative Head and Neck Cancer

Author(s): Makoto Tahara, MD, PhD1; Naomi Kiyota, MD, PhD2; Takeshi Kodaira, MD, PhD3; Hiroshi Nishino, MD, PhD4; Yukinori Asada, MD, PhD5; Hiroki Mitani, MD, PhD6; Yuji Hirayama, MD7; Yusuke Onozawa, MD8; Naoki Nishio, MD, PhD9; Nobuhiro Hanai, MD, PhD3; Akira Ohkoshi, MD, PhD10; Hiroki Hara, MD11; Nobuya Monden, MD, PhD12; Masato Nagaoka, MD, PhD13; Shujiro Minami, MD, PhD14; Kaoru Tanaka, MD, PhD15; Takashi Fujii, MD16; Seiichi Yoshimoto, MD, PhD17; Tsutomu Ueda, MD, PhD18; Yo Kishimoto, MD, PhD19; Akihiro Homma, MD, PhD20; Nobuhiko Oridate, MD, PhD21; Kenji Okami, MD, PhD22; Hirokazu Uemura, MD, PhD23; Katsunori Katagiri, MD, PhD24; Tomoko Yamazaki, MD, PhD, DDS25; Takahiro Asakage, MD, PhD26; Yuki Saito, MD, PhD27; Shigeyuki Murono, MD, PhD28; Junki Mizusawa, PhD29; Kenichi Nakamura, MD, PhD, MBA17; Ryuichi Hayashi, MD1; on behalf of the Head and Neck Cancer Study Group of the Japan Clinical Oncology Group (JCOG-HNCSG);
Source: DOI: 10.1200/JCO-25-01708
Original Article
Professional photo of Anjan J Patel, MD

Dr. Anjan Patel's Thoughts

This 5-year update should settle the debate for many of us: in 261 patients receiving postoperative chemoradiation for high-risk head and neck squamous cell carcinoma (SCC), weekly cisplatin (40 mg/m²) stayed noninferior to 3-weekly 100 mg/m², and 5-year overall survival (OS) actually ran numerically higher (71% vs 59%), with less acute toxicity and no meaningful difference in late toxicity. Before anyone reads superiority into that, the 3-weekly arm carried more T4, N2–3, and hypopharyngeal disease, the noninferiority margin was generous, and the cohort was all Japanese, small, and treated before immunotherapy. For our postop patients, weekly cisplatin now looks like a fully defensible standard rather than a fallback for patients who can’t tolerate the bolus dose.

ABSTRACT

The interim analysis of JCOG1008 demonstrated that chemoradiotherapy with cisplatin 40 mg/m2 once a week for seven cycles (weekly cisplatin) was noninferior in terms of overall survival (OS) compared with chemoradiotherapy with cisplatin 100 mg/m2 once every 3 weeks for three cycles (3-weekly cisplatin) for postoperative high-risk locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). This report presents the long-term follow-up results of JCOG1008. In this phase II/III trial, patients with postoperative high-risk LA-SCCHN were randomly assigned to receive either chemoradiotherapy with 3-weekly cisplatin or with weekly cisplatin. A total of 261 patients were enrolled. At the final analysis, with a median follow-up of 5.6 years, 5-year OS was 58.7% in the 3-weekly arm and 71.2% in the weekly arm (hazard ratio, 0.76 [95% CI, 0.52 to 1.12 [<1.32]]), confirming the noninferiority of the weekly regimen. Both 5-year relapse-free survival (RFS) and 5-year local RFS were numerically better in the weekly arm. No late adverse event showed more than a 10% difference between the two arms. In conclusion, 5-year follow-up confirmed that chemoradiotherapy with weekly cisplatin is noninferior in OS to chemoradiotherapy with 3-weekly cisplatin in patients with postoperative high-risk LA-SCCHN. These results further support the use of weekly cisplatin plus radiotherapy as a reasonable alternative for this patient population.

Author Affiliations

1National Cancer Center Hospital East, Kashiwa, Japan; 2Kobe University Hospital, Cancer Center, Kobe, Japan; 3Aichi Cancer Center Hospital, Nagoya, Japan; 4Jichi Medical University Hospital, Shimotsuke, Japan; 5Miyagi Cancer Center, Natori, Japan; 6Cancer Institute Hospital, Tokyo, Japan; 7Hyogo Cancer Center, Akashi, Japan; 8Shizuoka Cancer Center, Shizuoka, Japan; 9Nagoya University Hospital, Nagoya, Japan; 10Tohoku University Hospital, Sendai, Japan; 11Saitama Cancer Center, Ina, Japan; 12NHO Shikoku Cancer Center, Matsuyama, Japan; 13Jikei University School of Medicine, Tokyo, Japan; 14NHO Tokyo Medical Center, Tokyo, Japan; 15Kindai University Hospital, Sakai, Japan; 16Osaka International Cancer Institute, Osaka, Japan; 17National Cancer Center Hospital, Tokyo, Japan; 18Hiroshima University Hospital, Hiroshima, Japan; 19Kyoto University, Kyoto, Japan; 20Hokkaido University Hospital, Sapporo, Japan; 21Yokohama City University Hospital, Yokohama, Japan; 22Tokai University School of Medicine, Isehara, Japan; 23Nara Medical University, Kashihara, Japan; 24Iwate Medical University, Shiwa, Japan; 25Saitama Medical University International Medical Center, Hidaka, Japan; 26Institute of Science Tokyo Hospital, Tokyo, Japan; 27The University of Tokyo Hospital, Tokyo, Japan; 28Fukushima Medical University Hospital, Fukushima, Japan; 29Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan

Leave a Comment

Your email address will not be published. Required fields are marked *

Related Articles

Amivantamab in Recurrent/Metastatic Head and Neck Squamous Cell Cancer After Checkpoint Inhibitor and Chemotherapy: Pivotal Results From the Phase Ib/II OrigAMI-4 Study

Epidermal growth factor receptor (EGFR) and MET are overexpressed in recurrent/metastatic (R/M) head/neck squamous cell cancer (HNSCC).
Subcutaneous amivantamab administered every 3 weeks in participants with non-human papillomavirus R/M HNSCC after PD-(L)1 inhibitor and platinum-based chemotherapy. prior anti EGFR and HPV positive patients were excluded. In 102 participants, blind independent central review assessed objective response rates (ORRs) was 42% (around 20% for second line chemotherapy or cetuximab) the complete response rate was 15%. At a median follow-up of 11.8 months, median progression-free survival (PFS) and overall survival (OS) were 6.8 months and 12.5 months respectively. A non-chemotherapy option for HPV negative patients with promising outcome. Toxicity can still be an issue with those pts

Read More »

Pembrolizumab With or Without Lenvatinib as First-Line Therapy for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Phase III LEAP-010 Study

Combination improved progression-free survival (PFS) 6.2 months vs 2.8 months, hazard ratio (HR) 0.64 but not overall survival (OS) (15 months for combination vs 17.9 months for pembro), no safety concerns. Overall, although the combination demonstrated a clinically meaningful PFS advantage, the absence of an OS benefit limits its impact on standard first-line treatment, where survival remains the key endpoint.

Read More »

Neoadjuvant and Adjuvant Pembrolizumab in Locally Advanced Head and Neck Cancer

The KEYNOTE-689 trial evaluated perioperative pembrolizumab + SOC (surgery + adjuvant RT ± cisplatin) in resectable, locally advanced head and neck squamous-cell carcinoma (HNSCC) that is at least 1% PDL1 positive. The addition of pembrolizumab significantly improved 3-year event-free survival (EFS) in all PD-L1 subgroups: CPS≥10 (59.8% vs 45.9%), CPS≥1 (58.2% vs 44.9%), and the total population (57.6% vs 46.4%). Three-year overall survival (OS) also favored pembrolizumab: CPS≥10 (68.2% vs 59.2%), CPS≥1 (69.0% vs 60.2%), and total (68.4% vs 61.1%), though OS was not formally tested at this interim. Toxicities were as expected. Bottom line: perioperative pembro is now a part of the treatment paradigm for locally advanced HNCSCC with PDL1 expression.

Read More »
Load More