SAKK 21/12: a phase II trial of transdermal CR1447 in breast cancer patients
Objective: CR1447, a novel transdermal formulation of 4-hydroxytestosterone, has aromatase-inhibiting and androgen receptor (AR)-modulating properties (IC50 4.4 nM) with antitumor effects against AR-positive tumor cells in vitro. This trial investigated the efficacy and safety of CR1447 for patients...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Bioscientifica
2023-01-01
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| Series: | Endocrine Oncology |
| Subjects: | |
| Online Access: | https://eo.bioscientifica.com/view/journals/eo/2/1/EO-21-0009.xml |
| _version_ | 1797956007128727552 |
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| author | Marcus Vetter Karin M Rothgiesser Qiyu Li Hanne Hawle Wolfgang Schönfeld Karin Ribi Salome Riniker Roger von Moos Andreas Trojan Elena Kralidis Mathias Fehr Andreas Müller Beat Thürlimann |
| author_facet | Marcus Vetter Karin M Rothgiesser Qiyu Li Hanne Hawle Wolfgang Schönfeld Karin Ribi Salome Riniker Roger von Moos Andreas Trojan Elena Kralidis Mathias Fehr Andreas Müller Beat Thürlimann |
| author_sort | Marcus Vetter |
| collection | DOAJ |
| description | Objective: CR1447, a novel transdermal formulation of 4-hydroxytestosterone, has aromatase-inhibiting and androgen receptor (AR)-modulating properties (IC50 4.4 nM) with antitumor effects against AR-positive tumor cells in vitro. This trial investigated the efficacy and safety of CR1447 for patients with metastatic estrogen receptor-positive (A) and AR-positive triple-negative breast cancers (B).
Design and methods: (A) included patients with at most one prior endocrine therapy line without progression ≥6 months, whereas (B) included patients with ≤2 prior chemotherapy lines, all displaying advanced signs of disease. The primary endpoint was disease control at week 24 (DC24). The null hypothesis was DC24 ≤30% (A) and ≤15% (B). Thirty-seven patients were recruited (29 in (A) and 8 in (B)); accrual was stopped following an interim analysis demonstrating futility in (A) and slow accrual in (B).
Results: DC24 was attained in 5/21 (95% CI: 8.2–47.2) patients in (A) and none in (B). The median progression-free survival was 5.1 months (95% CI: 2.5–5.6) in (A) and 2.5 months (95% CI: 0.7–2.6) in (B). The median overall survival was 24.6 months (95% CI: 22.9–not applicable) in (A) and 10.8 months (95% CI: 3.3–10.9) in (B). CR1447 had a favorable safety profile without treatment-related grade 3–5 toxicities in (A). Especially no side effects linked to androgenic effects were observed.
Conclusions: Despite this trial being negative, the 24% DC24 rate in a second-line setting, and the prolonged partial response experienced by a patient, indicate activity. Further evaluation of CR1447 in endocrine-sensitive patients or combination trials appears warranted. |
| first_indexed | 2024-04-10T23:42:03Z |
| format | Article |
| id | doaj.art-ee02a98a152e445a96fded14df8d50d3 |
| institution | Directory Open Access Journal |
| issn | 2634-4793 |
| language | English |
| last_indexed | 2024-04-10T23:42:03Z |
| publishDate | 2023-01-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Endocrine Oncology |
| spelling | doaj.art-ee02a98a152e445a96fded14df8d50d32023-01-11T07:28:33ZengBioscientificaEndocrine Oncology2634-47932023-01-0121918https://doi.org/10.1530/EO-21-0009SAKK 21/12: a phase II trial of transdermal CR1447 in breast cancer patientsMarcus Vetter0Karin M Rothgiesser1Qiyu Li2Hanne Hawle3Wolfgang Schönfeld4Karin Ribi5Salome Riniker6Roger von Moos7Andreas Trojan8Elena Kralidis9Mathias Fehr10Andreas Müller11Beat Thürlimann12Medical Oncology, University Hospital Basel, Basel, Switzerland; Medical Oncology, Hematology and Immunotherapy, Cantonal Hospital Baselland, Medical University Clinic, Liestal, SwitzerlandSwiss Group for Clinical Cancer Research (SAKK) Coordinating Center, Bern, SwitzerlandSwiss Group for Clinical Cancer Research (SAKK) Coordinating Center, Bern, SwitzerlandSwiss Group for Clinical Cancer Research (SAKK) Coordinating Center, Bern, SwitzerlandCURADIS GmbH, Erlangen, GermanySwiss Group for Clinical Cancer Research (SAKK) Coordinating Center, Bern, Switzerland; IBCSG, International Breast Cancer Study Group, Bern, SwitzerlandBreast Cancer Center, Cantonal Hospital St. Gallen, St. Gallen, SwitzerlandMedical Oncology, Cantonal Hospital Chur, Chur, SwitzerlandMedical Oncology, Hirslanden Klinik Im Park, Zurich, SwitzerlandMedical Oncology, Cantonal Hospital Aarau, Aarau, SwitzerlandMedical Oncology, Hospital Thurgau, Thurgau, SwitzerlandMedical Oncology, Cantonal Hospital Winterthur, Winterthur, SwitzerlandBreast Cancer Center, Cantonal Hospital St. Gallen, St. Gallen, SwitzerlandObjective: CR1447, a novel transdermal formulation of 4-hydroxytestosterone, has aromatase-inhibiting and androgen receptor (AR)-modulating properties (IC50 4.4 nM) with antitumor effects against AR-positive tumor cells in vitro. This trial investigated the efficacy and safety of CR1447 for patients with metastatic estrogen receptor-positive (A) and AR-positive triple-negative breast cancers (B). Design and methods: (A) included patients with at most one prior endocrine therapy line without progression ≥6 months, whereas (B) included patients with ≤2 prior chemotherapy lines, all displaying advanced signs of disease. The primary endpoint was disease control at week 24 (DC24). The null hypothesis was DC24 ≤30% (A) and ≤15% (B). Thirty-seven patients were recruited (29 in (A) and 8 in (B)); accrual was stopped following an interim analysis demonstrating futility in (A) and slow accrual in (B). Results: DC24 was attained in 5/21 (95% CI: 8.2–47.2) patients in (A) and none in (B). The median progression-free survival was 5.1 months (95% CI: 2.5–5.6) in (A) and 2.5 months (95% CI: 0.7–2.6) in (B). The median overall survival was 24.6 months (95% CI: 22.9–not applicable) in (A) and 10.8 months (95% CI: 3.3–10.9) in (B). CR1447 had a favorable safety profile without treatment-related grade 3–5 toxicities in (A). Especially no side effects linked to androgenic effects were observed. Conclusions: Despite this trial being negative, the 24% DC24 rate in a second-line setting, and the prolonged partial response experienced by a patient, indicate activity. Further evaluation of CR1447 in endocrine-sensitive patients or combination trials appears warranted.https://eo.bioscientifica.com/view/journals/eo/2/1/EO-21-0009.xmlmetastatic breast cancerestrogen receptorandrogen receptorcr1447endocrine therapy |
| spellingShingle | Marcus Vetter Karin M Rothgiesser Qiyu Li Hanne Hawle Wolfgang Schönfeld Karin Ribi Salome Riniker Roger von Moos Andreas Trojan Elena Kralidis Mathias Fehr Andreas Müller Beat Thürlimann SAKK 21/12: a phase II trial of transdermal CR1447 in breast cancer patients Endocrine Oncology metastatic breast cancer estrogen receptor androgen receptor cr1447 endocrine therapy |
| title | SAKK 21/12: a phase II trial of transdermal CR1447 in breast cancer patients |
| title_full | SAKK 21/12: a phase II trial of transdermal CR1447 in breast cancer patients |
| title_fullStr | SAKK 21/12: a phase II trial of transdermal CR1447 in breast cancer patients |
| title_full_unstemmed | SAKK 21/12: a phase II trial of transdermal CR1447 in breast cancer patients |
| title_short | SAKK 21/12: a phase II trial of transdermal CR1447 in breast cancer patients |
| title_sort | sakk 21 12 a phase ii trial of transdermal cr1447 in breast cancer patients |
| topic | metastatic breast cancer estrogen receptor androgen receptor cr1447 endocrine therapy |
| url | https://eo.bioscientifica.com/view/journals/eo/2/1/EO-21-0009.xml |
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