Response to Larotrectinib as Primary Systemic Therapy for Unresectable Mammary Analog Secretory Carcinoma of the Parotid Gland

Presentation: D191
Topic: Salivary
Type: Poster
Date: Wednesday, May 1, 2019 (1:00 PM - 7:00 PM) | Thursday, May 2, 2019 (9:00 AM - 7:00 PM)
Session: Wednesday, May 1, 2019 (1:00 PM - 7:00 PM) | Thursday, May 2, 2019 (9:00 AM - 7:00 PM)
Authors: Haley N Kemp, MPAS, PAC1, Ly Nguyen1, Sandra Montez1, Diana Bell1, Filip Janku1, Maura L Gillison1, Ehab Y Hanna1, Nora Ku2, David Hong1, Xiuning Le1
Institution(s): 1MD Anderson Cancer Center, 2Loxo Oncology, Inc

Background: Mammary analogue secretory carcinoma (MASC) is a newly defined entity among salivary gland malignancies. They usually represent locally advanced disease with a strong male dominance.  Similar to their breast cancer counterpart, MASC tumors commonly harbor an ETV6-NTRK3 translocation, which makes MASC potentially susceptible to inhibition of TRK proteins.  Larotrectinib is a potent and highly selective small-molecule inhibitor of TRK proteins. Its efficacy has been demonstrated in an age- and tumor type- agnostic therapeutic program with an objective response rate of 75% per independent review in the first 55 sequentially enrolled NTRK fusion cancer patients. In this cohort, 3 patients with salivary gland carcinoma achieved complete response.

Case report: Our patient was a 37-year-old male who presented with one-year history of right parotid mass. At outside hospital, the surgical team attempted a parotidectomy, but was unable to completely excise the tumor due to facial nerve involvement. Pathological report showed low to intermediate grade secretory carcinoma with metastasis to two intraparotid lymph nodes. PET-CT disclosed a large right parotid mass, approximately at 5 x 2.4 x 2.0 cm^3 with no evidence of regional nodal or distant metastasis (Figure 1, left). The patient came to MD Anderson Cancer Center for further treatment recommendations.

Extensive local involvement of the entire parotid gland and stylomastoid space was confirmed and surgery was not recommended due to the involvement of the facial nerve and the high risk of not being able to achieve negative margins. Fluorescence in situ hybridization (FISH) of his tumor sample disclosed an ETV6-NTRK3 rearrangement, which was confirmed by NGS analysis. Subsequently, he was enrolled to the phase 2 larotrectinib trial, NAVIGATE (NCT02576431) and dosed at 100mg BID orally. He had an initial clinical response within 4 weeks with excellent control of facial pain and improved facial nerve function. He tolerated treatment well with mild fatigue and grade 1 elevated transaminases not requiring dose modification. He returned to work.  Serial MRI every 8 weeks showed gradual decrease in tumor size (Table 1). After 10 months of treatment, he has achieved a PR by RECIST (73% decrease in the primary mass from baseline) and PET-CT showed a complete metabolic response (Figure 1, right). Because of the complete metabolic response, it was deemed that there were no active residual tumor cells and surgery was deferred to the continuation of larotrectinib, which is ongoing.

Discussion: As MASC of salivary gland is a rare entity and access to TRK inhibitors is still limited to the clinical trial setting, we present our experience on one patient with unresectable ETV6-NTRK3 fusion MASC of the salivary gland who had achieved RECIST PR and complete metabolic response with larotrectinib monotherapy. This case highlights the efficacy of larotrectinib as primary systemic monotherapy in treating MASC of salivary gland, rendering an unresectable case to not needing surgery. We believe this case is valuable to other providers in the head and neck medical and surgical field treating salivary gland tumors and highlights the role of molecular profiling in this group of patients.

Fig. 1