Cancer Research and Treatment

Original Articles

Head and Neck cancer

Phase II Trial of Combined Durvalumab Plus Tremelimumab with Proton Therapy for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Hana Kim, Sehhoon Park, Hyun Ae Jung, Se-Hoon Lee, Keunchil Park, Yong Chan Ahn, Dongryul Oh, Myung-Ju Ahn; Cancer Res Treat. 2023;55(4):1104-1112. Published online May 17, 2023; DOI: https://doi.org/10.4143/crt.2023.502

Abstract PDF Supplementary Material PubReader ePub

Purpose
This phase II study investigated whether durvalumab/tremelimumab with proton therapy improves the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) in heavily treated recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) patients.
Materials and Methods
Patients who previously received more than one chemotherapy, including at least one platinum-based regimen, and who had at least two measurable lesions were enrolled. Patients received 1,500 mg durvalumab intravenously combined with 75 mg tremelimumab intravenously every 4 weeks for four cycles followed by 1,500 mg durvalumab every 4 weeks. After one cycle of the durvalumab/tremelimumab treatment, proton therapy was given with a total dose of 25 Gy in 5 Gy daily fractions to one of the measurable lesions. We also assessed the ORR in the target lesion outside the radiation field to evaluate the abscopal effect.
Results
Thirty-one patients were enrolled between March 2018 and July 2020. With 8.6 months of follow-up, the ORR was 22.6% (7/31), including one complete response and six partial responses. The median OS was 8.4 months (95% confidence interval [CI], 2.5 to 14.3) and the median PFS was 2.4 months (95% CI, 0.6 to 4.2). Among the 23 evaluable patients who completed proton therapy, the ORR was 30.4% (7/23). The median OS was 11.1 months (95% CI, 6.5 to 15.8), and the median PFS was 3.7 months (95% CI, 1.6 to 5.7). Grade 3 or higher adverse events were observed in six patients (19.4%) as follows: anemia (n=1), constipation (n=1), electrolyte imbalances (n=2), hyperglycemia (n=1), and pneumonia (n=1).
Conclusion
The combination of durvalumab/tremelimuab with proton therapy was tolerated well and had encouraging anti-tumor efficacy in non-irradiated tumor lesions of heavily treated HNSCC patients.

Citations

Citations to this article as recorded by

Abscopal effect in maxillary sinus cancer: Insights from two case reports and a literature review
Akihiro Sakai, Koji Ebisumoto, Hiroaki Iijima, Mayu Yamauchi, Daisuke Maki, Tsuyoshi Fukuzawa, Kenji Okami
Cancer Reports.2024;[Epub] CrossRef
Solid tumours showing oligoprogression to immune checkpoint inhibitors have the potential for abscopal effects
Makoto Ito, Souichiro Abe, Sou Adachi, Yukihiko Oshima, Arisa Takeuchi, Wataru Ohashi, Takashi Iwata, Tetsuya Ogawa, Akiko Ota, Yasuaki Kubota, Takahito Okuda, Kojiro Suzuki
Japanese Journal of Radiology.2024; 42(4): 424. CrossRef
Durvalumab with or without tremelimumab for patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a systematic review and meta-analysis
Xiao Han, Haidong Zhang, Kai Sun, Jing Li, Wanjuan Wu, Kai Liu, Zhenkun Yu
Frontiers in Immunology.2024;[Epub] CrossRef
Kaplan lecture 2023: lymphopenia in particle therapy
Marco Durante
International Journal of Radiation Biology.2024; 100(5): 669. CrossRef
Clinical application of high‐LET radiotherapy combined with immunotherapy in malignant tumors
Kexin Meng, Haijun Lu
Precision Radiation Oncology.2024; 8(1): 42. CrossRef
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Anchi Sun, Zhiwei Xing, Rongrong Lv, Pengyuan Niu, Bao Zhao, Shiyin Ma, Hui Li
Medical Oncology.2024;[Epub] CrossRef
A review and bibliometric analysis of global research on proton radiotherapy
Ge Song, Zhi Zheng, Yingming Zhu, Yaoting Wang, Song Xue
Medicine.2024; 103(19): e38089. CrossRef
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Rina Jiang, Mike Fritz, Syril Keena T. Que
Cancers.2024; 16(10): 1800. CrossRef
Radiotherapy and immunology
Liangliang Wang, Connor Lynch, Sean P. Pitroda, András Piffkó, Kaiting Yang, Amy K. Huser, Hua Laura Liang, Ralph R. Weichselbaum
Journal of Experimental Medicine.2024;[Epub] CrossRef
The Evolving Paradigm of Immunotherapy in Head-and-neck Squamous Cell Cancers
Riccardo Gili, Paolo Bossi
Journal of Head & Neck Physicians and Surgeons.2024; 12(1): 13. CrossRef
Neoadjuvant Immunotherapy in Head and Neck Cancers: A Paradigm Shift in Treatment Approach
Alessia Zotta, Maria Luisa Marciano, Francesco Sabbatino, Alessandro Ottaiano, Marco Cascella, Monica Pontone, Massimo Montano, Ester Calogero, Francesco Longo, Morena Fasano, Teresa Troiani, Fortunato Ciardiello, Fabiana Raffaella Rampetta, Giovanni Salz
Biomedicines.2024; 12(10): 2337. CrossRef
Emerging Radiotherapy Technologies for Head and Neck Squamous Cell Carcinoma: Challenges and Opportunities in the Era of Immunotherapy
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Cancers.2024; 16(24): 4150. CrossRef

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Apatinib Combined with Local Irradiation Leads to Systemic Tumor Control via Reversal of Immunosuppressive Tumor Microenvironment in Lung Cancer: Li-jun Liang, Chen-xi Hu, Yi-xuan Wen, Xiao-wei Geng, Ting Chen, Guo-qing Gu, Lei Wang, You-you Xia, Yong Liu, Jia-yan Fei, Jie Dong, Feng-hua Zhao, Yiliyar Ahongjiang, Kai-yuan Hui, Xiao-dong Jiang; Cancer Res Treat. 2020;52(2):406-418. Published online September 3, 2019; DOI: https://doi.org/10.4143/crt.2019.296

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to investigate the potential systemic antitumor effects of stereotactic ablative radiotherapy (SABR) and apatinib (a novel vascular endothelial growth factor receptor 2 inhibitor) via reversing the immunosuppressive tumor microenvironment for lung carcinoma.
Materials and Methods
Lewis lung cancer cells were injected into C57BL/6 mice in the left hindlimb (primary tumor; irradiated) and in the right flank (secondary tumor; nonirradiated). When both tumors grew to the touchable size, mice were randomly divided into eight treatment groups. These groups received normal saline or three distinct doses of apatinib (50 mg/kg, 150 mg/kg, and 200 mg/kg) daily for 7 days, in combination with a single dose of 15 Gy radiotherapy or not to the primary tumor. The further tumor growth/regression of mice were followed and observed.
Results
For the single 15 Gy modality, tumor growth delay could only be observed at the primary tumor. When combining SABR and apatinib 200 mg/kg, significant retardation of both primary and secondary tumor growth could be observed, indicated an abscopal effect was induced. Mechanism analysis suggested that programmed death-ligand 1 expression increased with SABR was counteract by additional apatinib therapy. Furthermore, when apatinib was combined with SABR, the composition of immune cells could be changed. More importantly, this two-pronged approach evoked tumor antigen–specific immune responses and the mice were resistant to another tumor rechallenge, finally, long-term survival was improved.
Conclusion
Our results suggested that the tumor microenvironment could be managed with apatinib, which was effective in eliciting an abscopal effect induced by SABR.

Citations

Citations to this article as recorded by

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