An open-label, noninferiority phase III RCT of weekly versus three weekly cisplatin and radical radiotherapy in locally advanced head and neck squamous cell carcinoma (ConCERT trial).
Authors: Atul Sharma, Manish Kumar, Suman Bhasker, Alok Thakar, Raja Pramanik, Ahitagni Biswas, akash kumar, Kapil Sikka, Amit Chirom Singh, Supriya Mallick, Rajeev Kumar, S.V.S. Deo, Aanchal Kakkar, Saphalta Baghmar, Amit Sehrawat, Pooja Sethi, Ashok Kumar, Sandeep Seth, Ashish Dutt Upadhyay, Sanjay Thulkar
Journal: Journal of Clinical Oncology (2022)

6004 Background: CCRT using 3 weekly cisplatin (DDP) 100mg/m 2 is considered standard nonsurgical option for LAHNSCC. Many prefer DDP 40 mg/m 2 weekly assuming this to be non inferior, with better radio sensitization, and less toxic but without robust supporting evidence. We designed this non inferiority trial to compare 3 weekly DDP to weekly DDP. Methods: Multicentric non inferiority RCT to compare DDP 100 mg/m 2 (Control as C) 3 weekly x 3 times to 40 mg/m 2 (Test as T) weekly DDP x7 times with concurrent RT as definitive therapy in non nasopharyngeal LAHNSCC. Primary objective was 2 years loco regional control (LRC) rates. Secondary endpoints included OS, PFS, toxicity, compliance, others. Assuming LRC of 60%, power of 80%, alpha error of 5%, and non inferiority margin of 10% 143 patients in each arm were required (including 10% non evaluable etc). Results: Between April 2018 and January 2021, 278 were randomised. Median age was 56 years (range 19-70), 89.6% were males. Primary sites were, oropharynx (59.6%), larynx (17.5%), hypopharynx, and oral cavity (11.6%) each. TNM stage was, stage III (29.1%), stage IVA (50.5%), and IVB (20.4%). 13% of oropharyngeal who were tested for p16 were found positive. ECOG PS was 0-1 in 78.9%. 135 in each arm were eligible for treatment and 132 received some form of treatment. Baseline characteristics (Chi square/Fisher’s exact test) were well balanced except higher number of patients with LVEF &lt;50% in T arm (p=0.035). 87.2% of patients in C arm, and 81.6% in T arm received ≥ 60 Grays (p=.94), 78.6% in C and 81.6% patients in T arm received ≥ 200 mg/m2 of DDP (p=.31). There were more treatment delays in treatment in C arm (p=NS). Treatments interruptions (p=0.035), hospitalizations (p=0.004), use of additional IV fluids (p= &lt;.001), mucositis (p=.029), myelosuppression (P=.021), renal toxicity (p=&lt;.001), vomiting ((p=.002), hyponatremia (p=.004) were all significantly more in C arm. There were 10 toxic deaths in C arm and 7 in T arm. 81.6% in C arm and 85.4% patients in T arm achieved CR+PR (p=.055). LRC rates at 2 years were 57.69% in C arm and 61.53% in T arm, with an absolute difference of 3.84% and (one sided 95% CI= -6.15, 13.80) which is within the pre defined non inferiority margin of -10%. Cumulative 2 year LRC rates were 52.6% in T and 47.4% in C (log-rank p=0.426; HR 0.86 [95%CI: 0.60-1.23]) by parametric survival estimates with an absolute difference of 5.2% (95%CI= -7.7, 18.2) again within pre defined margin. There was no significant difference in median time to loco-regional failure (C=21.23 months and T= NR; p=.45), OS (C=30.50 months and T= 25.46; p=.59) and PFS (C=20.60 months and T= 20.66; p=.46). Conclusions: This academic trial confirms that CCRT with weekly DDP is non inferior to 3 weekly DDP, is better tolerated with less interruptions, hospitalizations, and toxicity and should now be considered as one of the standards. Clinical trial information: CTRI/2018/03/012422.