852MO - REWRITE–GORTEC 2018-02: Radiotherapy-durvalumab without prophylactic neck irradiation in squamous cell carcinoma of the head and neck

Background

REWRITE, a multi-center single-arm phase II trial, was conducted to evaluate the neck control with durvalumab and RT restricted to the primary tumor site, with largely reduced-volume prophylactic neck irradiation (PNI) of N0 regions, in patients (pts) with SCCHN.

Methods

Pts with SCCHN T1-T4, N0-N2b non palpable, and only homolateral lymph node (LN) in radiological examinations, deemed ineligible for concomitant RT-CT were enrolled in this study. RT was delivered to the primary tumor and involved LN to a dose of 70Gy/33F over 6.5 weeks. Target volume included nodal level immediately adjacent to primary tumor/invaded LN to 52.8Gy, without any other PNI. Durvalumab was delivered during RT (1125 mg, Q3W) and was continued Q4W at 1500 mg for 6 months. The primary endpoint was regional nodal control rate in non-irradiated neck at 1 year, with an expected control rate of 92%.

Results

57 pts (median age=74 years, male = 72%) were included. The main primary tumor site was larynx (n=22, 39%) and oropharynx (n=15, 26%). The main T staging was T2 (N=23, 40%) and T4 (N=20, 35%). N staging was N1-N2b for 18 pts (31%). PS was 1 for 31 pts (54%) and 2 for 16 pts (28%). Durvalumab was delivered for 3 cycles during RT for 46 pts (80%). 29 pts (50%) could receive 6 months adjuvant durvalumab as planned. 56/57 pts were eligible for the evaluation of primary endpoint. 2 patients (3.6% [IC95% = 0.44; 12.31%]) had a progression disease in non-irradiated N0 neck at 1 year, corresponding to a neck control rate of 96.4%. 23 pts had a relapse, with a majority occurring in primary tumor (n=14). 1-year OS rate was 70% [95% CI 56-80%]. RT was well tolerated, with 4 G3 toxicity occurred in 3 pts (mucositis, dysphagia and pneumonia aspiration). Two pts had a G5 durvalumab related toxicity (interstitial pneumonia and diabetes) and 1 patient had a G5 durvalumab and RT related toxicity (Mucositis).

Conclusions

The primary endpoint was met showing that very limited N0 neck irradiation was associated with a very low probability of nodal relapse in non-irradiated neck in this subset of frail pts with T1-T4 SCCHN. The regional control rate compared favorably to that observed in case of large PNI.

Clinical trial identification

EU Clinical Trials Register: 2018-001976-39.

Editorial acknowledgement

Legal entity responsible for the study

GORTEC.

Funding

AstraZeneca.

Disclosure

All authors have declared no conflicts of interest.