Abstract
BackgroundAnti-EGFR-based therapies have limited success in HNSCC patients. Predictive biomarkers are greatly needed to identify the patients likely to be benefited from these targeted therapies. Here, we present the prognostic and predictive association of biomarkers in HPV-negative locally advanced (LA) HNSCC patients.MethodsTreatment-naive tumour tissue samples of 404 patients, a subset of randomised Phase 3 trial comparing cisplatin radiation (CRT) versus nimotuzumab plus cisplatin radiation (NCRT) were analysed to evaluate the expression of HIF1α, EGFR and pEGFR by immunohistochemistry and EGFR gene copy change by FISH. Progression-free survival (PFS), locoregional control (LRC) and overall survival (OS) were estimated by Kaplan–Meier method. Hazard ratios were estimated by Cox proportional hazard models.ResultsBaseline characteristics of the patients were balanced between two treatment groups (CRT vs NCRT) and were representative of the trial cohort. The median follow-up was of 39.13 months. Low HIF1α was associated with better PFS [HR (95% CI) = 0.62 (0.42–0.93)], LRC [HR (95% CI) = 0.56 (0.37–0.86)] and OS [HR (95% CI) = 0.63 (0.43–0.93)] in the CRT group. Multivariable analysis revealed HIF1α as an independent negative prognostic biomarker. For patients with high HIF1α, NCRT significantly improved the outcomes [PFS:HR (95% CI) = 0.55 (0.37–0.82), LRC:HR (95% CI) = 0.55 (0.36–0.85) and OS:HR (95% CI) = 0.54 (0.36–0.81)] compared to CRT. While in patients with low HIF1α, no difference in the clinical outcomes was observed between treatments. Interaction test suggested a predictive value of HIF1α for OS (P = 0.008).ConclusionsHigh HIF1α expression is a predictor of poor clinical response to CRT in HPV-negative LA-HNSCC patients. These patients with high HIF1α significantly benefited with the addition of nimotuzumab to CRT.Clinical trial registrationRegistered with the Clinical Trial Registry of India (Trial registration identifier—CTRI/2014/09/004980).
Highlights
Anti-epidermal growth factor receptor (EGFR)-based therapies have limited success in Head and neck squamous cell carcinomas (HNSCCs) patients
Patil et al recently reported improved progression-free survival (PFS) [hazard ratio, hazard ratios (HR) = 0.69 (0.53–0.89)] and locoregional control (LRC) [HR = 0.67 (0.50–0.89)] in unselected locally advanced (LA)-HNSCC (> 94% HPVnegative) patients treated with nimotuzumab plus cisplatin radiation compared to the patients treated with only cisplatin radiation in a Phase 3-randomised trial conducted in India.[6]
Prognostic biomarkers are extensively studied in HNSCCs, but they have limited utility in patients’ treatment decisions
Summary
Anti-EGFR-based therapies have limited success in HNSCC patients. Predictive biomarkers are greatly needed to identify the patients likely to be benefited from these targeted therapies. CONCLUSIONS: High HIF1α expression is a predictor of poor clinical response to CRT in HPV-negative LA-HNSCC patients. Addition of anti-EGFR monoclonal antibody (mAb) to the chemoradiation regimen has largely met with limited success in these patients.[3] Nimotuzumab (h-R3) is a humanised IgG1 mAb against EGFR shown to have low toxicity as compared to other anti-EGFR mAbs.[4,5] Patil et al recently reported improved progression-free survival (PFS) [hazard ratio, HR (95% CI) = 0.69 (0.53–0.89)] and locoregional control (LRC) [HR (95% CI) = 0.67 (0.50–0.89)] in unselected LA-HNSCC (> 94% HPVnegative) patients treated with nimotuzumab plus cisplatin radiation compared to the patients treated with only cisplatin radiation in a Phase 3-randomised trial conducted in India.[6]
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