First-in-human study of SBRT and adenosine pathway blockade to potentiate the benefit of immunochemotherapy in early-stage luminal B breast cancer: results of the safety run-in phase of the Neo-CheckRay trial
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| Názov: | First-in-human study of SBRT and adenosine pathway blockade to potentiate the benefit of immunochemotherapy in early-stage luminal B breast cancer: results of the safety run-in phase of the Neo-CheckRay trial |
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| Autori: | Alex De Caluwe, Emanuela Romano, Philip Poortmans, Andrea Gombos, Elisa Agostinetto, Guilherme Nader Marta, Zoe Denis, Stylianos Drisis, Christophe Vandekerkhove, Antoine Desmet, Catherine Philippson, Ligia Craciun, Isabelle Veys, Denis Larsimont, Marianne Paesmans, Dirk Van Gestel, Roberto Salgado, Christos Sotiriou, Martine Piccart-Gebhart, Michail Ignatiadis, Laurence Buisseret |
| Zdroj: | J Immunother Cancer Journal for ImmunoTherapy of Cancer, Vol 11, Iss 12 (2023) Journal for ImmunoTherapy of Cancer |
| Informácie o vydavateľovi: | BMJ, 2023. |
| Rok vydania: | 2023 |
| Predmety: | Clinical/Translational Cancer Immunotherapy, Adult, Radiosurgery -- methods, Breast Neoplasms -- drug therapy -- radiotherapy, Adenosine, Radiotherapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Breast Neoplasms, Sciences bio-médicales et agricoles, B7-H1 Antigen -- therapeutic use, Middle Aged, Radiosurgery, Prognosis, Combined Modality Therapy, B7-H1 Antigen, 3. Good health, Humans, Female, Immunotherapy, Human medicine, 10. No inequality, RC254-282, Aged |
| Popis: | Background Luminal B breast cancer (BC) presents a worse prognosis when compared with luminal A BC and exhibits a lower sensitivity to chemotherapy and a lower immunogenicity in contrast to non-luminal BC subtypes. The Neo-CheckRay clinical trial investigates the use of stereotactic body radiation therapy (SBRT) directed to the primary tumor in combination with the adenosine pathway inhibitor oleclumab to improve the response to neo-adjuvant immuno-chemotherapy in luminal B BC. The trial consists of a safety run-in followed by a randomized phase II trial. Here, we present the results of the first-in-human safety run-in. Methods The safety run-in was an open-label, single-arm trial in which six patients with early-stage luminal B BC received the following neo-adjuvant regimen: paclitaxel q1w×12 → doxorubicin/cyclophosphamide q2w×4; durvalumab (anti-programmed cell death receptor ligand 1 (PD-L1)) q4w×5; oleclumab (anti-CD73) q2w×4 → q4w×3 and 3×8 Gy SBRT to the primary tumor at week 5. Surgery must be performed 2–6 weeks after primary systemic treatment and adjuvant therapy was given per local guidelines, RT boost to the tumor bed was not allowed. Key inclusion criteria were: luminal BC, Ki67≥15% or histological grade 3, MammaPrint high risk, tumor size≥1.5 cm. Primary tumor tissue samples were collected at three timepoints: baseline, 1 week after SBRT and at surgery. Tumor-infiltrating lymphocytes, PD-L1 and CD73 were evaluated at each timepoint, and residual cancer burden (RCB) was calculated at surgery. Results Six patients were included between November 2019 and March 2020. Median age was 53 years, range 37–69. All patients received SBRT and underwent surgery 2–4 weeks after the last treatment. After a median follow-up time of 2 years after surgery, one grade 3 adverse event (AE) was reported: pericarditis with rapid resolution under corticosteroids. No grade 4–5 AE were documented. Overall cosmetical breast evaluation after surgery was ‘excellent’ in four patients and ‘good’ in two patients. RCB results were 2/6 RCB 0; 2/6 RCB 1; 1/6 RCB 2 and 1/6 RCB 3. Conclusions This novel treatment combination was considered safe and is worth further investigation in a randomized phase II trial. Trial registration number NCT03875573. |
| Druh dokumentu: | Article Other literature type |
| Popis súboru: | 1 full-text file(s): application/pdf |
| Jazyk: | English |
| ISSN: | 2051-1426 |
| DOI: | 10.1136/jitc-2023-007279 |
| Prístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/38056900 https://doaj.org/article/a5ee6654546a4d7e98521bceca85490a https://hdl.handle.net/10067/2021080151162165141 https://repository.uantwerpen.be/docstore/d:irua:21267 |
| Rights: | CC BY NC URL: http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ (http://creativecommons.org/licenses/by-nc/4.0/) . |
| Prístupové číslo: | edsair.doi.dedup.....3602068b2a11a569e1d3815ab6f05a8a |
| Databáza: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Background Luminal B breast cancer (BC) presents a worse prognosis when compared with luminal A BC and exhibits a lower sensitivity to chemotherapy and a lower immunogenicity in contrast to non-luminal BC subtypes. The Neo-CheckRay clinical trial investigates the use of stereotactic body radiation therapy (SBRT) directed to the primary tumor in combination with the adenosine pathway inhibitor oleclumab to improve the response to neo-adjuvant immuno-chemotherapy in luminal B BC. The trial consists of a safety run-in followed by a randomized phase II trial. Here, we present the results of the first-in-human safety run-in. Methods The safety run-in was an open-label, single-arm trial in which six patients with early-stage luminal B BC received the following neo-adjuvant regimen: paclitaxel q1w×12 → doxorubicin/cyclophosphamide q2w×4; durvalumab (anti-programmed cell death receptor ligand 1 (PD-L1)) q4w×5; oleclumab (anti-CD73) q2w×4 → q4w×3 and 3×8 Gy SBRT to the primary tumor at week 5. Surgery must be performed 2–6 weeks after primary systemic treatment and adjuvant therapy was given per local guidelines, RT boost to the tumor bed was not allowed. Key inclusion criteria were: luminal BC, Ki67≥15% or histological grade 3, MammaPrint high risk, tumor size≥1.5 cm. Primary tumor tissue samples were collected at three timepoints: baseline, 1 week after SBRT and at surgery. Tumor-infiltrating lymphocytes, PD-L1 and CD73 were evaluated at each timepoint, and residual cancer burden (RCB) was calculated at surgery. Results Six patients were included between November 2019 and March 2020. Median age was 53 years, range 37–69. All patients received SBRT and underwent surgery 2–4 weeks after the last treatment. After a median follow-up time of 2 years after surgery, one grade 3 adverse event (AE) was reported: pericarditis with rapid resolution under corticosteroids. No grade 4–5 AE were documented. Overall cosmetical breast evaluation after surgery was ‘excellent’ in four patients and ‘good’ in two patients. RCB results were 2/6 RCB 0; 2/6 RCB 1; 1/6 RCB 2 and 1/6 RCB 3. Conclusions This novel treatment combination was considered safe and is worth further investigation in a randomized phase II trial. Trial registration number NCT03875573. |
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| ISSN: | 20511426 |
| DOI: | 10.1136/jitc-2023-007279 |