Dose-finding and efficacy confirmation trial of the superselective intra-arterial infusion of cisplatin and concomitant radiotherapy for locally advanced maxillary sinus cancer (JCOG1212): Results of the efficacy confirmation phase in the T4a cohort.
Authors: Akihiro Homma, Kazuto Matsuura, Rikiya Onimaru, Daisuke Yoshida, Hirotaka Shinomiya, Akira Ohkoshi, Ryuichi Hayashi, Yuki Saito, Hiroyuki Tachibana, Kiyoto Shiga, Tsutomu Ueda, Yukinori Asada, Hirokazu Uemura, Akira Seto, Takeshi Beppu, Kazuki Ishikawa, Masashi Mikami, Kenichi Nakamura, Haruhiko Fukuda, Naomi Kiyota
Journal: Journal of Clinical Oncology (2022)

6014 Background: The JCOG1212 trial seeks to evaluate the safety and efficacy of the superselective intra-arterial infusion of high-dose cisplatin with concomitant radiotherapy (RADPLAT) for patients (pts) with T4aN0M0 or T4bN0M0 maxillary sinus squamous cell carcinomas (MS-SCC). T4aN0M0 MS-SCC requires radical surgery with or without complete resection of the orbital contents as a standard treatment, which results in disfigurement and functional impairment. We herein report the results of the efficacy confirmation phase in the T4a cohort. Methods: Eligible pts with T4aN0M0 MS-SCC were registered and received cisplatin 100 mg/m 2 intra-arterially weekly for 7 weeks with concomitant radiotherapy (total 70 Gy) as determined by the results of the previous dose-finding phase. The trial investigated the 3-year overall survival (3yr OS) of RADPLAT to demonstrate its non-inferiority to surgery, the current standard of care, and its superiority to IV-CRT, which is used for pts refusing surgery. From the results of observational study undertaken by our group, the historical control for the 3yr OS was set at 80% for surgery and 65% for IV-CRT. A margin of 15% was set to demonstrate its non-inferiority to surgery and superiority to IV-CRT. Thus, when the lower boundary of the two-sided 90% confidence interval (CI) exceeds the threshold of 65% for 3yr OS, RADPLAT will be confirmed as the new standard. A sample size of 62 was required to achieve 80% power with a one-sided 5% significance level. Results: From April 2014 to August 2018, 65 pts were registered in the T4a cohort from 18 institutions, consisting of 54 males and 11 females with a median age of 64 years (range, 40-78 years) and ECOG PS 0/1 (58/7). After the exclusion of one ineligible patient, 64 pts were included in the primary analysis of efficacy and safety. The complete clinical remission rate was 73.4% (47/64, 95% CI, 60.9%-83.7%), with 15 showing CR and 32 showing good PR. The median follow-up was 4.5 years in all eligible pts and the primary endpoint for 3yr-OS was 82.8% (90% CI, 73.4%-89.2%), which met the prespecified hypothesis. The 3yr event-free survival and 3yr local event-free survival were 60.9% (95% CI, 47.9%-71.7%) and 65.6 % (95% CI, 52.5%-75.8%), respectively. With regard to acute adverse events, neutropenia (≥ grade 3), increased creatinine (≥ grade 2), hearing impairment (≥ grade 2), mucositis (≥ grade 3), and stroke (≥ grade 2) were observed in 14.1%, 3.1%, 3.1%, 20.3%, and 1.6% of pts, respectively. One treatment-related death due to a thromboembolic event was reported. Conclusions: RADPLAT is non-inferior to surgery and superior to IV-CRT for pts with T4aN0M0 MS-SCCs and showed manageable toxicities. Therefore, RADPLAT, as well as surgery, should be considered the new standard treatment option for these pts. Clinical trial information: UMIN000013706.