Survival benefit of HER2-targeted or androgen deprivation therapy in salivary duct carcinoma

Abstract

Background: The efficacy and safety of human epidermal growth factor receptor 2 (HER2)-targeted therapy and androgen deprivation therapy (ADT) for locally advanced or recurrent or metastatic (LA/RM) salivary duct carcinoma (SDC) have been reported in prospective studies. However, the survival benefit of these therapies to conventional therapy remains controversial, and whether HER2-targeted therapy or ADT should be chosen in HER2- and androgen receptor (AR)-positive SDC patients remains unknown. Methods: Overall, 323 LA/RM SDC patients treated at seven institutions between August 1992 and June 2020 were retrospectively enrolled. The primary aim was to analyze the effect of HER2-targeted therapy and ADT on overall survival from the diagnosis of LA/RM disease to death from any cause (OS1). The secondary indicators included the overall response rate (ORR), clinical benefit rate (CBR), overall survival from therapy initiation for LA/RM disease (OS2), progression-free survival (PFS), time to second progression (PFS2), duration of response (DoR), and duration of clinical benefit (DoCB) of HER2-targeted therapy or ADT as first-line therapy for HER2-positive/AR-positive SDC. Results: Patients treated with HER2-targeted therapy or ADT had longer OS1 than those treated without these therapies (Median OS1: historical control, 21.6 months; HER2-targeted therapy, 50.6 months; ADT, 32.8 months; HER2-targeted therapy followed by ADT, 42.4 months; and ADT followed by HER2-targeted therapy, 45.2 months, p < 0.001). Among HER2-positive/AR-positive SDC patients, although HER2-targeted therapy had better ORR, CBR, and PFS than those of ADT as first-line therapy, we found no significant differences between HER2-targeted therapy and ADT regarding OS2, PFS2, DoR, and DoCB. Conclusion: Patients treated with HER2-targeted therapy and ADT showed longer survival in LA/RM SDC. HER2-targeted therapy can be recommended prior to ADT for HER2-positive/AR-positive SDC. It is warranted to establish a biomarker that could predict the efficacy of clinical benefit or better response in ADT.

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“…Studies with anti-HER-2 therapies showed that ORR was more than 50% in patients with SDC. Chemotherapy combined with HER-2 blockade included docetaxel in three studies [23, 24, 26], pertuzumab in one [25], and docetaxel with pertuzumab in another [28]. Trials with feasible ORR only targeted SDC [23, 24, 26, 28] and not the whole SGC.…”

“…Chemotherapy combined with HER-2 blockade included docetaxel in three studies [23, 24, 26], pertuzumab in one [25], and docetaxel with pertuzumab in another [28]. Trials with feasible ORR only targeted SDC [23, 24, 26, 28] and not the whole SGC. HER-2-targeted therapy cannot be applied to a large range of patients with SGC because HER-2, except in SDC, is not commonly expressed in SGC [29].…”

“…Because HER family proteins play a critical role in carcinoma proliferation [17], anti-HER family therapies are used in various types of carcinoma [18]. Previous reports regarding anti-HER family therapies for patients with SGC are summarized in Table 2 [19][20][21][22][23][24][25][26][27][28]. Studies with anti-HER-2 therapies showed that ORR was more than 50% in patients with SDC.…”

“…In our study, more than half of the patients were patients with SDC. As anti-HER-2 and anti-androgen receptor therapies have been effective in patients with SDC [26,[31][32][33][34][35], SDC would be suitable for treatment with molecular-targeted therapy, including EGFR blockade. Molecular-targeted therapy is mainly divided into tyrosine kinase inhibitors and molecule-targeted antibodies.…”

“…Expression of the corresponding protein is necessary for reactivity in molecular-targeted therapy. All the previous studies regarding anti-HER-2 therapies subjected to HER-2 positive SGC patients [19,[23][24][25][26]28]. However, previous studies using anti-EGFR therapies with poor clinical outcomes included patients with negative EGFR [21,22,27].…”