NCCN Endorses Goserelin in Salivary Gland Tumors in New Head and Neck Cancers Guidelines

On October 24, 2023, TerSera Therapeutics LLC announced that The National Comprehensive Cancer Network (NCCN) Head and Neck Cancers Panel recommended the GnRH agonist goserelin in certain circumstances for patients with recurrent, unresectable, or metastatic salivary gland tumors who were not eligible for surgery or radiation therapy.¹

Version 1.2024 of the NCCN Head and Neck Cancers Guidelines, which was released on October 9, 2023, included a category 2B recommendation for goserelin, identifying it as “useful in certain circumstances,” for patients with recurrent, unresectable, or metastatic salivary gland tumors with no radiation therapy or surgery option. The recommendation noted that there was no preferred regimen at this indication and that the choice of systemic therapy should be tailored to individual patients based on their therapy goals, performance status, and other characteristics.²

"The NCCN Head and Neck Cancers Panel has recognized goserelin as an option for patients with recurrent, unresectable, or metastatic salivary gland tumors," Nancy Martin, MD, PharmD, chief medical officer at TerSera, said in a news release.¹

The recommendation was supported by findings from the phase 2 Yatagarasu (NCT04325828) and BTCRC-HN17-111 (NCT03942653) studies. Yatagarasu enrolled patients with far locally advanced or recurrent/metastatic and androgen receptor (AR)-expressing salivary gland carcinoma; eligible patients received oral apalutamide (Erleada)240 mg once daily plus subcutaneous goserelin 3.6 mg once every 28 days. BTCRC-HN17-111 enrolled patients with incurable recurrent or metastatic AR-expressing salivary gland tumors who had not prior androgen deprivation therapy (ADT) or immune checkpoint therapy; eligible patients were treated with subcutaneous goserelin 3.6 mg once every 4 weeks and intravenous pembrolizumab (Keytruda) 200 mg every 3 weeks beginning 14 days after the start of goserelin therapy.^3,4

Findings from Yatagarasu showed that primary response-evaluable patients (n = 24) achieved an objective response rate (ORR) of 25% (95% CI, 9.8%-46.7%), all of which were partial responses (PRs). The median duration of response was not estimable (NE; 95% CI, 6.64-NE), and the median time to response was 1.87 months (range, 1.7-3.7). The clinical benefit rate (CBR) and disease control rate were 50.0% (95% CI, 29.1%-70.9%) and 70.8% (95% CI, 48.9%-87.4%), respectively. Investigators noted that although the study did not meet its primary end point of ORR by central review per RECIST v1.1 criteria, the combination displayed clinically meaningful activity with a well-tolerated safety profile.³

Data from BTCRC-HN17-111 demonstrated that patients who received pembrolizumab plus goserelin (n = 9) achieved an ORR of 22%; all responses were PRs in patients with ductal carcinomas. Six additional patients experienced stable disease (SD) for a CBR of 88%. The 6-month progression-free survival rate was 63% (95% CI, 19%-85%). Study authors concluded that the combination of pembrolizumab and goserelin displayed preliminary efficacy and was well tolerated in the first stage of the trial.⁴

Finally, results from a retrospective study revealed that patients who received ADT with once daily bicalutamide (Casodex) 150 mg or bicalutamide 50 mg once daily plus goserelin 3.6 mg every 4 weeks (n = 35) experienced a PR rate of 18% and an SD rate of 32%, for a CBR of 50%. The median PFS was 4 months (95% CI, 3-5). The median overall survival for patients who received any androgen deprivation therapy was 17 months (95% CI, 10-24) compared with 5 months (95% CI, 1‐9) among patients who received best supportive care (n = 43; P = .02). Investigators concluded by stating that they recommend ADT for the treatment of patients with AR-positive salivary duct carcinoma.⁵

Notably, goserelin has not yet been approved by the FDA for the treatment of patients with salivary gland carcinoma.¹

References

1. Goserelin included in the National Comprehensive Cancer Network (NCCN) head and neck cancers guidelines. News release.TerSera Therapeutics LLC. October 24, 2023. Accessed November 8, 2023. https://www.prnewswire.com/news-releases/goserelin-included-in-the-national-comprehensive-cancer-network-nccn-head-and-neck-cancers-guidelines-301965604.html#:~:text=%22The%20NCCN%20Head%20and%20Neck,Chief%20Medical%20Officer%20at%20TerSera
2. NCCN. Clinical Practice Guidelines in Oncology. Head and neck cancers, version 1.2024. Accessed November 8, 2023. https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf
3. Honma Y, Monden N, Yamazaki K, et al. Yatagarasu: a single-arm, open-label, phase 2 study of apalutamide (APA) plus goserelin (GOS) for patients (pts) with far locally advanced or recurrent/metastatic (fLA/RM) and androgen receptor (AR)-expressing salivary gland carcinoma (SGC). J Clin Oncol. 2022;40(suppl 16):6079. doi:10.1200/JCO.2022.40.16_suppl.6079
4. Patel M, Fujioka N, Pease DF, et al. BTCRC-HN17-111, a phase 2 trial of ADT (goserelin) in combination with pembrolizumab for patients with advanced salivary gland tumors expressing androgen receptor (AR). J Clin Oncol. 2022;40(suppl 16):e18091. doi:10.1200/JCO.2022.40.16_suppl.e18091
5. Boon E, van Boxtel W, Buter J, et al. Androgen deprivation therapy for androgen receptor–positive advanced salivary duct carcinoma: a nationwide case series of 35 patients in The Netherlands. Head Neck. 2018;40(3):605-613. doi:10.1002/hed.25035