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  • Author: Connie Siew Poh Yip x
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Janice Ser Huey Tan Division of Radiation Oncology, National Cancer Centre Singapore, Hospital Boulevard, Singapore

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Timothy Kwang Yong Tay Department of Pathology, Singapore General Hospital, Singapore

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Enya Hui Wen Ong Division of Radiation Oncology, National Cancer Centre Singapore, Hospital Boulevard, Singapore

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Michael Fehlings ImmunoScape, 1 Scotts Road #24-10, Singapore

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Daniel Shao-Weng Tan Division of Medical Oncology, National Cancer Centre Singapore, Hospital Boulevard, Singapore

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Nadiah Binte Sukma Department of Pathology, Singapore General Hospital, Singapore

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Eileen Xueqin Chen Department of Pathology, Singapore General Hospital, Singapore

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Jen-Hwei Sng Department of Pathology, Singapore General Hospital, Singapore

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Connie Siew Poh Yip Division of Radiation Oncology, National Cancer Centre Singapore, Hospital Boulevard, Singapore

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Kok Hing Lim Department of Pathology, Singapore General Hospital, Singapore

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Darren Wan-Teck Lim Division of Medical Oncology, National Cancer Centre Singapore, Hospital Boulevard, Singapore

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Narayanan Gopalakrishna Iyer Division of Surgical Oncology, National Cancer Centre Singapore, Hospital Boulevard, Singapore

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Jacqueline Siok Gek Hwang Department of Pathology, Singapore General Hospital, Singapore

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Melvin Lee Kiang Chua Division of Radiation Oncology, National Cancer Centre Singapore, Hospital Boulevard, Singapore

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Mei-Kim Ang Division of Medical Oncology, National Cancer Centre Singapore, Hospital Boulevard, Singapore

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Objective

Anaplastic thyroid cancer (ATC) is an aggressive disease associated with poor outcomes and resistance to therapies. Our study aim was to evaluate the activity of a combinatorial regimen of sandwich sequencing of pembrolizumab immunotherapy and hypofractionated radiotherapy (RT).

Methods

In this case series, patients with ATC received hypofractionated RT (QUAD-shot) and intravenous pembrolizumab 200 mg every 3–4 weeks. Pembrolizumab was continued until disease progression or up till 24 months. Concurrent lenvatinib treatment was allowed. Primary endpoint was best overall response (BOR) and progression-free survival (PFS). Additionally, we performed immune profiling of circulating T cells in a responder to investigate the immune response to our combinatorial treatment.

Results

At median follow-up of 32.6 months (IQR: 26.4–38.8), of a cohort of five patients, BOR was 80%; with two complete responses (CR) and two partial responses (PR). Patients who achieved CR remained disease-free at last follow-up. Median PFS was 7.6 months (IQR: 6.2–NR), and 1-year PFS and overall survival rate was 40% (95% CI: 13.7–100) for both. Treatment was well-tolerated, with mostly grade 1–2 adverse events. Immune profiling of one partial responder revealed an increase in activated CD4 and CD8 T cells post-QUAD-shot RT, which was further enhanced during the maintenance phase of pembrolizumab.

Conclusion

Herein, we report a case series of five patients with ATC, with two long-term survivors who were treated with surgical debulking followed by QUAD-shot RT and pembrolizumab, possibly due to synergy of local and systemic treatments in activating anti-tumour immunogenic cytotoxicity. This regimen warrants further investigation in a larger cohort of patients.

Open access