What question did this study set out to answer?

This study aims to establish the maximum tolerated dose of erlotinib and evaluate patient outcomes after reirradiation for recurrent HNSCC.

April 13, 2026Open Access

Survival and Quality of Life After Reirradiation With Concurrent Pemetrexed/Erlotinib Followed by Maintenance Erlotinib for Recurrent/Second Primary Head and Neck Squamous Cell Carcinoma: Final Report of a Phase I/II Trial

Key Points

This study aims to establish the maximum tolerated dose of erlotinib and evaluate patient outcomes after reirradiation for recurrent HNSCC.
Conducted a multi-institutional phase I/II clinical trial.
Enrolled patients with recurrent/second primary HNSCC within the 45 Gy isodose line.
Administered concurrent pemetrexed/erlotinib followed by maintenance erlotinib.
Used a 3+3 design to determine maximum tolerated dose.
Collected adverse events and quality of life outcomes at multiple time points.
Maximum tolerated dose of erlotinib was established at 125 mg.
Observed 25 out of 27 patients with grade 3+ adverse events.
Median progression-free survival was 8.5 months, and overall survival was 11.2 months.
One-year progression-free and overall survival rates were 33% and 44%, respectively.
Quality of life assessments showed no significant changes from baseline to six months.

Abstract

Introduction For patients with recurrent/second primary (R/SP) head and neck squamous cell carcinoma (HNSCC) within a previously irradiated volume that is not amenable to surgical resection, reirradiation may be employed with curative intent. The optimal regimen for concurrent chemotherapy with reirradiation has not been determined. We sought to determine the maximum tolerated dose (MTD) of concurrent erlotinib in patients treated with definitive reirradiation, to determine disease response, PFS, and OS in patients treated with concurrent pemetrexed/erlotinib and maintenance erlotinib, and to describe quality of life (QOL) over time in this cohort. Methods A multi-institutional phase I/II clinical trial enrolled patients with R/SP HNSCC with disease within the 45 Gy isodose line. Patients were treated with concurrent pemetrexed/erlotinib followed by maintenance erlotinib. The MTD of concurrent erlotinib was determined using a 3+3 design. Adverse events (AEs) and patient-reported outcomes of QOL, including the Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN) and MD Anderson Dysphagia Inventory (MDADI) and the Performance Status Scale for Head and Neck Cancer (PSS-HN), were collected at baseline, 1, 6, and 12 months after RT. Results In total, 27 patients were enrolled: 15 in phase I and 12 in phase II. Median prior RT dose was 66 Gy, and median reirradiation dose was 60 Gy. Two DLTs were observed in the 150 mg group; the MTD of erlotinib was 125 mg. Twenty-five of 27 patients experienced grade 3+ AEs. Best response was complete, partial, stable, and progressive in seven, seven, five, and four patients, respectively. Median PFS was 8.5 months, and median OS was 11.2 months. One-year PFS and OS rates were 33% and 44%, respectively. Mean FACT-HN trial outcome index ranged from 52 to 58 across all time points. Mean MDADI global and composite scores ranged from 57-75 to 56-66 over time, respectively. No differences in mean FACT-HN, MDADI, and PSS-HN scores were identified from baseline to six months. Conclusions In patients with R/SP HNSCC treated with reirradiation with concurrent pemetrexed/erlotinib followed by maintenance erlotinib, toxicity is high, disease control is consistent with prior reirradiation studies, and patient-reported QOL is unchanged within a short-term follow-up of six months.

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