Phase II study of trastuzumab-pkrb and docetaxel anhydrous combination therapy in recurrent or metastatic salivary ductal carcinomas (KCSG HN18-08/KM11).

Abstract

6018 Background: Salivary gland cancers (SGCs) are relatively rare, accounting for 1-6% of all neoplasms of the head and neck, have diverse disease course with respect to origin and pathology. Salivary duct carcinoma (SDC) is the most aggressive tumor subtype of primary SGC, showing high rates of local recurrence and distant metastases. In regard to previous studies which reported a high prevalence of HER2 positivity in SDCs, we conducted a single-arm, phase II study to evaluate the antitumor activity and safety of Herzuma (a trastuzumab biosimilar which demonstrated an equivalent efficacy to reference trastuzumab) in combination with docetaxel anhydrous (Nanoxel) in patients with HER2-positive advanced SDCs. Methods: Eligible patients had histologically confirmed HER2-positive (defined as IHC≥2+ and/or FISH HER2/CEN17 ratio ≥2.0) recurrent/metastatic SDC, or subtypes of SGC that were pathologically similar to SDC (excluding ACCs). They received Herzuma (8mg/kg i.v. loading dose, followed by 6mg/kg i.v.) and Nanoxel (75mg/m2 i.v.) every 3 weeks. The primary endpoint was the investigator-assessed objective response rate (ORR) according to RECIST v1.1. Secondary endpoints were overall survival (OS), progression-free survival (PFS), and safety. The calculated sample size was 43 patients for H1 of ORR ≥40%. Safety was evaluated by CTCAE v4.0. Results: A total of 43 patients were enrolled. Patient characteristics included: median age 60 (range 35–81); 86% male; 84% ECOG1; 84% SDC, 9% adenocarcinoma, 2% high grade mucoepidermoid carcinoma, and 5% other subtypes. Confirmed ORR was seen in 67% (95% CI, 52–81). No patient had a complete response as their BOR, 29 (67%) had a partial response, 11 (26%) had stable disease, 1 (2%) had progressive disease, and 2 (5%) were unevaluable. The DCR was 93% (95% CI, 81–99). The median PFS and OS were 8.2 months (95% CI, 6.7–9.7) and 23.3 months (95% CI, 19.9–26.7), respectively. Thirty-eight (88%) patients experienced a treatment-related AE (TRAE), with 15 (35%) patients experiencing ≥grade 3 TRAE including: neutropenia (10), febrile neutropenia (4), anemia (1), sepsis (1), anaphylaxis (1), decreased LVEF (1). There were no treatment-related deaths. Conclusions: The study met the primary endpoint of ORR. Herzuma and Nanoxel combination therapy demonstrated a promising treatment outcome in patients with HER2-positive recurrent/metastatic SDC. Clinical trial information: NCT03614364.