Session Item

We herein report the results of the interim analysis of a phase 2 clinical trial to assess the overall response rate(ORR) to gemcitabine & cisplatin(GC) based neoadjuvant chemotherapy(NACT) followed by dysphagia optimised intensity modulated radiotherapy(Do-IMRT) with concurrent weekly cisplatin in patients with locally advanced nasopharyngeal carcinoma(LA-NPC).

We hypothesised that compared to historical control, the use of NACT  followed by cisplatin-based Do-IMRT in stage II-IVA NPC will improve the complete response(CR) rate from 70% to 90% & the ORR from 80% to 95% at 3 months after completion of CRT. The target sample was 25. Patients with stage II-IVA NPC received 3 cycles of 3-weekly NACT with cisplatin(80mg/m² IV divided over D1,D2) & gemcitabine(1g/m² IV D1,D8) followed by Do-IMRT (65Gy,60Gy,54Gy/30fractions/6weeks to high, intermediate & low risk PTVs respectively by simultaneous integrated boost) with concurrent cisplatin(40mg/m² IV weekly). Clinicoradiological response assessment was done at 3 weeks post-NACT & 3 months post-CRT using RECISTv1.1. PFS & OS were assessed by Kaplan-Meier method. Swallowing evaluation was done by using MD Anderson Dysphagia Inventory(MDADI) questionnaire at baseline, immediately and 3 & 6 months post-CRT. Serial changes in MDADI composite scores(CS) at all time points were analysed by Friedman test &  pair wise comparison was done by Wilcoxon signed rank test. Serial plasma EBV-DNA titres were assessed by real-time PCR.

Out of a total of 30 screened patients, 23 were eligible and recruited in this study from 25-Sep-2020 to 01-Jan-2022. The database was locked on 15-June-2022. The median age at diagnosis was 34 years (range:15-65 years). 82.6% of the patients had undifferentiated NPC & 91.3% stained positive for EBV-LMP1. 21 out of 23 patients completed NACT with 9.1% & 95.5% CR rate & ORR to NACT, respectively. 20 out of these 21 patients had been started on CRT & 18 had completed CRT. The CR rate & ORR after CRT were 78.6% & 92.9% respectively. 1 patient had locoregional progressive disease(PD) and 1 had solitary lung metastasis. The median plasma EBV-DNA copies/ml. dropped from 544(at baseline) to 2(after NACT) (p<0.001) & subsequently became nil in all evaluable patients at 1 & 3 months post-CRT. The median duration of follow-up was 13.06 months. The median PFS & OS had not been reached. The actuarial PFS & OS rates were 100% & 90.3% at 1 year and 80.8% & 73.6% at 2 years, respectively. The incidence of severe haematological & non-haematological toxicities were 17.4% & 4.3% during NACT and 20% & 25% during CRT, respectively. No severe late toxicity was noted. Median MDADI-CS dipped from 94.73 to 56.84 post-CRT, with a steady rise to 89.71 and 93.15 at 3 & 6 months post-CRT, respectively (p-value<0.001), due to resolution of acute swallowing toxicities.

GC-based NACT followed by cisplatin-enhanced Do-IMRT was feasible and led to high ORR &  favourable toxicity profile in patients with LA-NPC.