- Design:
- Multicenter, open-label, phase II / III noninferiority RCT:
- In resected, high-risk LA-SCCHN:
- Features such as positive / close margin and / or ENE
- In resected, high-risk LA-SCCHN:
- Randomized to:
- q3-weekly cisplatin 100 mg m² × 2 to 3 with RT vs
weekly cisplatin 40 mg / m² with the same RT
- q3-weekly cisplatin 100 mg m² × 2 to 3 with RT vs
- Primary (phase III):
- Overall survival (OS); NI margin HR 1.32 PubMed
- Multicenter, open-label, phase II / III noninferiority RCT:
- Patients and follow-up:
- 261 enrolled:
- 132 q3-weekly
- 129 weekly
- Planned third interim analysis
- Median follow-up 2.2 years at the time of the report;:
- Updated curves included in the article figures PubMed
- Efficacy:
- Noninferiority met
- OS:
- Weekly noninferior to q3-weekly:
- HR 0.69, 99.1% CI 0.374–1.273; one-sided P for NI 0.0027 < 0.0043
- Kaplan–Meier curves:
- Show overlapping survival with no detriment for weekly dosing PubMed
- Weekly noninferior to q3-weekly:
- Relapse-free survival (RFS):
- KM curves presented:
- No signal of inferiority for weekly dosing in subgroup displays PubMed
- KM curves presented:
- Safety (clinically meaningful reductions with weekly dosing):
- Grade ≥ 3 neutropenia:
- 35% weekly vs 49% q3-weekly
- Infections (grade ≥ 3):
- 7% weekly vs 12% q3-weekly
- Renal impairment and hearing impairment:
- Less frequent with weekly cisplatin:
- Favors organ preservation of kidney / ear
- Less frequent with weekly cisplatin:
- Treatment-related deaths:
- 0 in q3-weekly
- 2 (1.6%) in weekly arm (rare) PubMed
- Grade ≥ 3 neutropenia:
- 261 enrolled:
- Interpreting the curves and endpoint strategy:
- The trial was powered for OS noninferiority, not superiority:
- The KM OS plots (and RFS plots) are consistent with therapeutic equivalence on survival while achieving lower nephro / ototoxicit:
- A clinically relevant trade-off in the post-op population where competing risks (nutrition, wound healing, dysphagia) matter PubMed
- The KM OS plots (and RFS plots) are consistent with therapeutic equivalence on survival while achieving lower nephro / ototoxicit:
- The trial was powered for OS noninferiority, not superiority:
- External context and follow-ups:
- Editorial perspective:
- JCOG1008 provides some of the strongest evidence supporting weekly cisplatin as a standard alternative in the adjuvant setting: PMC
- Subsequent / supplementary analyses continue to explore renal events and adherence:
- Without overturning the primary conclusion of noninferior OS with improved tolerability PMC+1
- Subsequent / supplementary analyses continue to explore renal events and adherence:
- JCOG1008 provides some of the strongest evidence supporting weekly cisplatin as a standard alternative in the adjuvant setting: PMC
- Editorial perspective:
- Practical takeaways for tumor board:
- Either schedule is acceptable:
- For post-op high-risk patients (positive / close margin and / or ENE):
- Weekly 40 mg / m² is a guideline-consistent alternative to 100 mg / m² q3-weekly:
- With less nephrotoxicity and ototoxicity PubMed
- Weekly 40 mg / m² is a guideline-consistent alternative to 100 mg / m² q3-weekly:
- For post-op high-risk patients (positive / close margin and / or ENE):
- Maintain attention to cumulative dose (aim ≥ 200 mg /m² overall when feasible) and supportive care:
- Weekly scheduling can improve deliverability in frailer patients.:
- General principle supported across cisplatin CRT literature MDPI
- Weekly scheduling can improve deliverability in frailer patients.:
- Either schedule is acceptable:
- Key citation:
- Kiyota N, et al. JCOG1008—J Clin Oncol. 2022;40:1980–1990.
Rodrigo Arrangoiz MS, MD, FACS, FSSO 