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Clinical Trial
. 2021 Sep:162:60-67.
doi: 10.1016/j.radonc.2021.06.037. Epub 2021 Jul 5.

High-dose irradiation in combination with non-ablative low-dose radiation to treat metastatic disease after progression on immunotherapy: Results of a phase II trial

Roshal R Patel  1 , Kewen He  2 , Hampartsoum B Barsoumian  3 , Joe Y Chang  3 , Chad Tang  3 , Vivek Verma  3 , Nathan Comeaux  3 , Stephen G Chun  3 , Saumil Gandhi  3 , Mylene T Truong  4 , Jeremy J Erasmus  4 , David S Hong  5 , Percy P Lee  3 , Matthew S Ning  3 , Quynh-Nhu Nguyen  3 , John V Heymach  6 , Mehmet Altan  6 , George Blumenschein  6 , Frank V Fossella  6 , Duygu Sezen  7 , Dawei Chen  1 , Brett W Carter  4 , Michael A Davies  8 , Isabella C Glitza  6 , Adi Diab  8 , Renata Ferrarotto  6 , Maria E Cabanillas  9 , Ying Yuan  10 , Shalin J Shah  3 , Edwin R Parra  11 , Baohua Sun  11 , Maria Angelica Cortez  3 , James W Welsh  12
Affiliations
Clinical Trial

High-dose irradiation in combination with non-ablative low-dose radiation to treat metastatic disease after progression on immunotherapy: Results of a phase II trial

Roshal R Patel et al. Radiother Oncol. 2021 Sep.

Abstract

Aim: To report early findings from a phase II trial of high-dose radiotherapy (HD-RT) with or without low-dose RT (LD-RT) for metastatic cancer.

Methods: Eligible patients had metastatic disease that progressed on immunotherapy within 6 months. Patients were given either HD-RT (20-70 Gy total; 3-12.5 Gy/f), or HD-RT + LD-RT (0.5-2 Gy/f up to 1-10 Gy total) to separate lesions, with continued immunotherapy. Radiographic response was assessed per RECIST 1.1 and Immune-Related Response Criteria (irRC). Primary endpoints: (1) 4-month disease control (DCR, complete/partial response [CR/PR] or stable disease [SD]) or an overall response (ORR, CR/PR) at any point in ≥10% of patients, per RECIST 1.1; (2) dose-limiting toxicity within 3 months not exceeding 30%. Secondary endpoint was lesion-specific response.

Results: Seventy-four patients (NSCLC, n = 38; melanoma n = 21) were analyzed (39 HD-RT and 35 HD-RT + LD-RT). The median follow-up time was 13.6 months. The primary endpoint was met for 72 evaluable patients, with a 4-month DCR of 42% (47% [16/34] vs. 37% [14/38] in HD-RT + LD-RT vs. HD-RT, P = 0.38), and 19% ORR at any time (26% [9/34] vs. 13% [5/38] in HD-RT + LD-RT vs. HD-RT, P = 0.27). Three patients had toxicity ≥grade 3. LD-RT lesion response (53%) was improved compared to nonirradiated lesions in HD-RT + LD-RT (23%, P = 0.002) and HD-RT (11%, P < 0.001). T- and NK cell infiltration was enhanced in lesions treated with LD-RT.

Conclusions: HD-RT plus LD-RT safely improved lesion-specific response in patients with immune resistant solid tumors by promoting infiltration of effector immune cells into the tumor microenvironment.

Keywords: Immunotherapy resistance; Low-dose radiotherapy; Metastatic cancer; Radioimmunotherapy; Salvage radiotherapy.

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