No abstract

Objectives. Salivary duct carcinoma (SDC) is a rare and aggressive malignancy with high mortality and poor response to treatment. A significant fraction of SDCs are HER2 positive. This retrospective review examines HER2 testing in SDC and the outcome of trastuzumab-based therapy in adjuvant and palliative settings. Methods. A total of 13 patients with SDC and HER2/neu expression by immunohistochemistry of 1-3ϩ were treated with trastuzumab in adjuvant (n ϭ 8) or palliative (n ϭ 5) setting. Adjuvant therapy consisted of concurrent radiation and chemotherapy with weekly paclitaxel, carboplatin, and trastuzumab (TCH) for 6 weeks followed by TCH for 12 weeks and trastuzumab alone for 1 year. Palliative treatment for metastatic disease consisted of TCH every 3 weeks for 6 cycles followed by trastuzumab for variable time periods with or without second-line chemotherapy for progression. All patients had fluorescence in situ hybridization testing for HER2/ neu gene amplification. Results. The median duration of follow-up was 27 months (range: 8 -48 months). In all, 62% of adjuvant patients (5/8) had no evidence of disease more than 2 years from completion of therapy. All patients with metastatic disease (5/5 patients) responded to treatment with TCH. One patient achieved a complete response and remains with no evidence of disease 52 months after initiation of TCH. The median duration of response was 18 months (range: 8 -52 months). Conclusion. HER2/neu positivity and treatment with trastuzumab correlated well with long-term survival and response in our patients. Based on this data, we propose that HER2/neu status be examined routinely in all patients with SDCs and the treatment be directed accordingly. The Oncologist 2013;18: 294 -300 Implications for Practice: Salivary duct carcinoma (SDC) is an extremely rare and aggressive type of salivary gland cancer with high morbidity and mortality. Current treatment options of surgery with or without radiation therapy provide limited benefit. Conventional chemotherapeutic agents have been utilized in the palliative setting with modest results. Randomized prospective clinical trials are difficult due to the rarity of the disease. Newer treatment strategies are needed to improve outcomes. At DanaFarber Cancer Institute, we treated HER2 positive SDCs with trastuzumab-based therapy with excellent results. Patients with HER2 positive SDC received a combination of paclitaxel, carboplatin and trastuzumab (TCH) in the palliative or adjuvant setting. Although the results below are from a small cohort of patients, treatment with trastuzumab correlated well with long-term survival and response to therapy. The unique application of this treatment in the adjuvant and palliative setting is practice changing and could have direct clinical implications.

Purpose: Targeting mutations leading to PI3K/mTOR/Akt activation are of interest in thyroid cancer (TC). We evaluated the efficacy of everolimus in aggressive, radioactive iodine refractory (RAIR) TC and correlated tumor mutational profiling with response. Exploratory medullary and anaplastic TC cohorts were included.Experimental Design: This single-arm, multi-institutional phase II study was conducted from 2009-2013 in patients with incurable RAIR TC who had radiographic progression six months prior to enrollment. The primary endpoint was progression-free survival (PFS) with a median follow-up of 31.8 months. The study is closed to enrollment but treatment and follow-up are ongoing. A targeted next-generation sequencing platform was used for mutational analysis.Results: Thirty-three patients with differentiated TC (DTC), 10 with medullary TC (MTC), and 7 with anaplastic TC (ATC) enrolled. For the DTC cohort, median PFS was 12.9 months (95% CI, 7.3-18.5) with a 2-year PFS of 23.6% (95% CI, 10.5-39.5). Median OS was not reached; 2-year OS was 73.5% (95% CI, 53.8-85.8). Among ATC patients, 1 had a partial response and was progression-free until 17.9 months post study entry and one had disease stability for 26 months, respectively. The genomically profiled cohort enriched for PI3K/mTOR/Akt alterations. PI3K/mTOR/Akt mutated ATC subgroups appeared to benefit from everolimus. Treatmentrelated adverse events were as anticipated. Conclusion:Everolimus has significant anti-tumor activity in TC. While genomic profiling does not currently guide therapeutic selection in TC patients, these data have important implications when considering the use of an mTOR inhibitor in an era of precision medicine.

BACKGROUND Oral mucositis (OM) is a significant toxicity of induction chemotherapy for locally advanced head and neck cancer (LAHNC). The safety and tolerability of AG013, an oral rinse containing recombinant Lactococcus lactis secreting mucosal protectant human trefoil factor 1 (hTFF1), was evaluated in a phase 1b study in LAHNC subjects who received induction with cisplatin, 5‐fluorouracil, with or without docetaxel. Preliminary efficacy data were also obtained. METHODS A total of 25 of 52 LAHNC subjects who were followed during induction cycle 1 developed ulcerative oral mucositis (UOM; World Health Organization grade > 2) and were randomized to AG013:placebo (5:2 ratio) for cycle 2. Dosing schedules of 1, 3, or 6 times daily were evaluated (2 × 1011, 6 × 1011, and 1.2 × 1012 colony forming units per day, respectively). OM was evaluated daily from cycle 2, day 1 through 14, using World Health Organization criteria. Pharmacokinetic assessment was also conducted. RESULTS AG013 bacteria were not detected in blood. Oral live AG013 bacterial and hTFF1 levels in saliva and oral mucosa were equivalent among treatment groups. The most frequently occurring adverse events were nausea, oral pain, fatigue, diarrhea, and mucosal inflammation. Only 12% (3 of 25 adverse events), mainly nausea, were attributed to the investigational medicinal product: AG013 or placebo. Efficacy analysis showed a 35% reduction in percentage of days with UOM in AG013‐subjects versus placebo. All placebo subjects experienced ≥ 2 days of UOM, whereas 29% of AG013 subjects had UOM for 0 or 1 day. AG013 use resulted in fewer unscheduled office and emergency room visits. No differences were noted in mouth and throat soreness, opioid use, or gastrostomy tube placement. CONCLUSIONS AG013 was safe and well tolerated. Preliminary efficacy data support further study. Cancer 2013;119:4268–4276. © 2013 American Cancer Society.