Meta-Analysis Indicates Addition of Taxane to Cisplatin/5-FU Induction Improves Outcome in Locally Advanced Head and Neck Cancers
Cisplatin plus fluorouracil (5-FU) induction chemotherapy has been compared with taxane (docetaxel or paclitaxel), cisplatin, and 5-FU in randomized trials in locoregionally advanced head and neck cancers. An updated individual patient data meta-analysis reported in the Journal of Clinical Oncology by Pierre Blanchard, MD, and colleagues in the Meta-Analysis of Chemotherapy in Head and Neck Cancer, Induction Project, Collaborative Group was performed to compare outcomes with taxane/cisplatin/5-FU vs cisplatin/5-FU induction therapy in this setting. Taxane/cisplatin/5-FU was associated with significant improvements in overall survival, progression-free survival, locoregional failure, and distant failure.
Study Details
The analysis included five randomized trials representing 1,772 patients with locoregionally advanced head and neck cancers, with updated individual patient data being retrieved for all trials. Patients had a mean age of 56 years, and most were male (90%) and had ECOG performance status of 0 or 1 (99%). Most tumors were locally advanced (T3-T4 in 85%, N2-3 in 62%); 39% of the tumors arose in the oropharynx and 25% in the hypopharynx.
Improved Overall Survival
Median follow-up was 4.9 years. The hazard ratio (HR) for death for taxane/cisplatin/5-FU vs cisplatin/5-FU was 0.79 (95% confidence interval [CI] = 0.70–0.89, P < .001), with an absolute overall survival benefit of 7.4% at 5 years for taxane/cisplatin/5-FU (35.0% vs 42.4%). Heterogeneity was significant (P = .08, I2 = 51%) and related to one trial; after exclusion of this trial, there was no heterogeneity (P = .99, I2 = 0%) and the hazard ratio for death was 0.72 (95% CI = 0.630.83). There was no interaction between treatment effect and patient covariates of age, sex, performance status, tumor stage, or site.
The difference in overall survival was related to a reduction of head and neck cancer mortality in favor of taxane/cisplatin/5-FU (HR = 0.74, 95% CI = 0.65–0.84, P < .001), with an absolute difference at 5 years of 9.3% (50.8% vs 60.1%). No significant difference in noncancer mortality was observed (HR = 1.12, 95% CI = 0.82–1.51, P = .47).
Improved Progression-Free Survival, Locoregional and Distant Failure
Taxane/cisplatin/5-FU induction was also associated with significant improvements in: progression-free survival, with a hazard ratio of 0.78 (95% CI = 0.69-0.87, P < .001) and an absolute benefit at 5 years of 7.1% (28.4% vs 35.5%); locoregional failure, with a hazard ratio of 0.79 (95% CI = 0.66–0.94, P = .007) and an absolute benefit of 7.4% at 5 years (44.2% vs 51.6%); and distant failure, with a hazard ratio of 0.63 (95% CI = 0.45–0.89, P = .009) and an absolute benefit of 6.4% at 5 years (13.7% vs 20.1%). There was no heterogeneity between trials for progression-free survival, locoregional failure, and distant failure analyses.
Compliance with concomitant chemotherapy differed significantly (P = .02) between taxane/cisplatin/5-FU and cisplatin/5-FU for trials with planned chemoradiotherapy, with more patients in the taxane/cisplatin/5-FU arms receiving the concomitant chemotherapy as planned (49% vs 43%) and fewer not receiving any chemotherapy (31% vs 38%). Compliance with radiation therapy was also significantly better in the taxane/cisplatin/5-FU arms, with 73% starting the planned therapy vs 67% in the cisplatin/5-FU arms (P = .004).
Although no data on tumor response were collected, the investigators posited that these differences might be attributable to a higher response rate with taxane/cisplatin/5-FU, with fewer cisplatin/5-FU patients being candidates by protocol for radiation therapy or concomitant treatment. Among patients who started chemoradiotherapy, there was no difference in compliance with concomitant chemotherapy.
The investigators concluded: “Although induction [taxane/cisplatin/5-FU] is superior to [cisplatin/5-FU] in terms of [overall survival, progression-free survival], and locoregional and distant control, its precise role compared with upfront [chemoradiotherapy] in the management of locoregionally advanced head and neck squamous cell carcinomas remains to be defined.”
For full disclosures of the study authors, visit jco.ascopubs.org.
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