Paclitaxel/carboplatin with or without cetuximab for treatment of carcinoma with unknown primary (PACET-CUP): Results of a multi-center randomized phase II AIO trial.

Abstract

4120 Background: Paclitaxel/carboplatin is one of the standard regimens for empiric treatment of patients (pts) with carcinoma with unknown primary (CUP) when a specific therapy is not available. The EGFR antibody cetuximab demonstrated efficacy in several cancer types. Methods: Pts with newly diagnosed non-resectable, undifferentiated or adeno-CUP were randomized to 6 cycles paclitaxel 175 mg/m² and carboplatin AUC 5 every three weeks (arm A) or the same chemotherapy plus cetuximab (400 mg/m², then 250 mg/m² weekly; arm B) at 13 German centres. CUP pts belonging to favorable prognosis groups [i.e. women with isolated peritoneal carcinomatosis or axillary lymph node metastases, men with retroperitoneal lymph nodes, pts with specific tumor entities according to histology / immunohistochemistry] were excluded from the trial. The primary endpoint was progression-free survival (PFS), secondary endpoints were response rate (RR) and overall survival (OS). Results: Between 03/2010 and 03/2017, 72 pts were randomized to arm A and 78 pts to arm B. The median age was 61 years, 84 pts were male (40 and 44 pts in arm A and B). 58 pts had a performance status (PS) of 0 (24 and 34 pts), 89 pts a PS of 1 (47 and 42 pts in arm A and B), and one patient in arm A had a PS of 2. PFS and OS did not differ between arms. The median PFS was 3.7 [95%CI: 3.0 - 4.4] and 4.6 [95%CI: 2.9 - 6.2] months in arms A and B (HR 0.98 [95%CI: 0.70-1.37]), the median OS 8.1 [95%CI: 6.5 - 9.8] and 7.4 [95%CI: 5.1 - 9.6] months in arms A and B, respectively (HR 1.10 [95%CI: 0.77 - 1.56]). There was a statistically non-significant trend towards a higher RR with cetuximab: 11 pts had a partial response in arm A (15% [95%CI: 7.9 - 26%]), and 17 pts in arm B (22% [95%CI: 13%-33%], p = 0.30). Twenty-five pts in each arm had stable disease, and 36 pts in each arm had progressive disease or were not evaluable for response. Conclusions: This study represents one of the largest trials in pts with CUP and demonstrates that randomized trials are feasible in this disorder with high medical need. The outcome of CUP pts in the unfavorable prognosis group was not improved by adding cetuximab to empiric therapy paclitaxel/carboplatin. Clinical trial information: NCT00894569.