5753 - Trastuzumab plus docetaxel in patients with advanced HER2–positive salivary duct carcinoma: Exploratory biomarker analyses

Background

A phase II trial of trastuzumab plus docetaxel in patients with advanced HER2–positive salivary duct carcinoma (SDC) showed 70% of the overall response rate. However, biomarkers which predict survival in this population remain unknown.

Methods

A total of 91 patients with HER2–positive SDC treated with trastuzumab plus docetaxel were included. Age, sex, ECOG performance status (PS), status of visceral metastases, previous treatment, previous docetaxel exposure, previous combined androgen blockade, the best overall response to the treatment, pretreatment serum C-reactive protein (CRP) level, modified Glasgow Prognosis Score (mGPS), HER2 status (immunohistochemistry [IHC] score, HER2/CEP17 ratio, HER2 copy number, overall positivity according to ASCO/CAP Guidelines), mutational status of PIK3CA, HRAS, and TP53, IHC score of AR, Ki-67, CK5/6, p53, HER3, Akt, PI3K, FOXA1, adipophilin, mTOR and PTEN were assessed and correlated with progression-free survival (PFS) and overall survival (OS).

Results

Treatment response (PR or CR vs. SD or PD) and PTEN IHC score (1+ – 3+ vs. 0) were related with favorable PFS (hazard ratio [HR], 0.25 and 0.39, respectively) and OS (HR, 0.29 and 0.36, respectively). CRP (≥ 0.50 mg/dL) was related with shorter PFS (HR, 2.28) and OS (HR 4.46). Presence of previous treatment and mTOR IHC (1+ – 3+ vs. 0) had significant predictive value of better PFS (HR 0.47 and 0.22, respectively) but not significantly related with OS. ECOG PS of 1-2 (vs. 0), presence of visceral metastasis, and mGPS of 1-2 (vs. 0) had significant relationship with shorter OS but not with PFS. Neither previous docetaxel exposure nor previous combined androgen blockade did not affect the survival outcome. HER2, PIK3CA, HRAS and TP53 status did not related with survival.

Conclusions

Although HER2 status did not correlated with survival, its downstream factors PTEN and mTOR can serve as predictive biomarkers in patients with advanced SDC treated with trastuzumab plus docetaxel. Serum CRP level may predict survival of this population.

Clinical trial identification

UMIN000009437, Released on 03/12/2012.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

MEXT/JSPS.

Disclosure

All authors have declared no conflicts of interest.