Oral metronomic vinorelbine combined with endocrine therapy in hormone receptor-positive HER2-negative breast cancer: SOLTI-1501 VENTANA window of opportunity trial
Abstract Background The biological effect of oral metronomic vinorelbine (mVNB) alone or in combination with endocrine therapy in patients with hormone receptor-positive (HR+)/HER2-negative breast cancer has been scarcely addressed. Methods Postmenopausal women with untreated stage I–III HR+/HER2-ne...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-09-01
|
| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13058-019-1195-z |
| _version_ | 1818439638286598144 |
|---|---|
| author | Barbara Adamo Meritxell Bellet Laia Paré Tomás Pascual Maria Vidal José A. Pérez Fidalgo Salvador Blanch Noelia Martinez Laura Murillo Patricia Gómez-Pardo Ana López-González Kepa Amillano Jordi Canes Patricia Galván Blanca González-Farré Xavier González Patricia Villagrasa Eva Ciruelos Aleix Prat |
| author_facet | Barbara Adamo Meritxell Bellet Laia Paré Tomás Pascual Maria Vidal José A. Pérez Fidalgo Salvador Blanch Noelia Martinez Laura Murillo Patricia Gómez-Pardo Ana López-González Kepa Amillano Jordi Canes Patricia Galván Blanca González-Farré Xavier González Patricia Villagrasa Eva Ciruelos Aleix Prat |
| author_sort | Barbara Adamo |
| collection | DOAJ |
| description | Abstract Background The biological effect of oral metronomic vinorelbine (mVNB) alone or in combination with endocrine therapy in patients with hormone receptor-positive (HR+)/HER2-negative breast cancer has been scarcely addressed. Methods Postmenopausal women with untreated stage I–III HR+/HER2-negative breast cancer were randomized (1:1:1) to receive 3 weeks of letrozole (LTZ) 2.5 mg/day, oral mVNB 50 mg 3 days/week, or the combination. The primary objective was to evaluate, within PAM50 Luminal A/B disease, if the anti-proliferative effect of LTZ+mVNB was superior to monotherapy. An anti-proliferative effect was defined as the mean relative decrease of the PAM50 11-gene proliferation score in combination arm vs. both monotherapy arms. Secondary objectives included the evaluation of a comprehensive panel of breast cancer-related genes and safety. An unplanned analysis of stromal tumor-infiltrating lymphocytes (sTILs) was also performed. PAM50 analyses were performed using the nCounter®-based Breast Cancer 360™ gene panel, which includes 752 genes and 32 signatures. Results Sixty-one patients were randomized, and 54 paired samples (89%) were analyzed. The main patient characteristics were mean age of 67, mean tumor size of 1.7 cm, mean Ki67 of 14.3%, stage I (55.7%), and grades 1–2 (90%). Most baseline samples were PAM50 Luminal A (74.1%) or B (22.2%). The anti-proliferative effect of 3 weeks of LTZ+mVNB (− 73.2%) was superior to both monotherapy arms combined (− 49.9%; p = 0.001) and mVNB (− 19.1%; p < 0.001). The anti-proliferative effect of LTZ+mVNB (− 73.2%) was numerically higher compared to LTZ (− 65.7%) but did not reach statistical significance (p = 0.328). LTZ+mVNB induced high expression of immune-related genes and gene signatures, including CD8 T cell signature and PDL1 gene and low expression of ER-regulated genes (e.g., progesterone receptor) and cell cycle-related and DNA repair genes. In tumors with ≤ 10% sTILs at baseline, a statistically significant increase in sTILs was observed following LTZ (paired analysis p = 0.049) and LTZ+mVNB (p = 0.012). Grade 3 adverse events occurred in 3.4% of the cases. Conclusions Short-term mVNB is well-tolerated and presents anti-proliferative activity alone and in combination with LTZ. The high expression of immune-related biological processes and sTILs observed with the combination opens the possibility of studying this combination with immunotherapy. Further investigation comparing these biological results with other metronomic schedules or drug combinations is warranted. Trial registration NCT02802748, registered 16 June 2016. |
| first_indexed | 2024-12-14T17:59:38Z |
| format | Article |
| id | doaj.art-6c3ac59779994d10b293d6741850b501 |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-12-14T17:59:38Z |
| publishDate | 2019-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-6c3ac59779994d10b293d6741850b5012022-12-21T22:52:28ZengBMCBreast Cancer Research1465-542X2019-09-0121111210.1186/s13058-019-1195-zOral metronomic vinorelbine combined with endocrine therapy in hormone receptor-positive HER2-negative breast cancer: SOLTI-1501 VENTANA window of opportunity trialBarbara Adamo0Meritxell Bellet1Laia Paré2Tomás Pascual3Maria Vidal4José A. Pérez Fidalgo5Salvador Blanch6Noelia Martinez7Laura Murillo8Patricia Gómez-Pardo9Ana López-González10Kepa Amillano11Jordi Canes12Patricia Galván13Blanca González-Farré14Xavier González15Patricia Villagrasa16Eva Ciruelos17Aleix Prat18Department of Medical Oncology, Hospital Clínic de BarcelonaVall d’Hebrón University Hospital/Vall d’Hebron Institute of Oncology (VHIO)Translational Genomics and Targeted Therapeutics in Solid Tumors, IDIBAPSDepartment of Medical Oncology, Hospital Clínic de BarcelonaDepartment of Medical Oncology, Hospital Clínic de BarcelonaHospital Clínico Universitario de Valencia/INCLIVA/CIBERONCFundación Instituto Valenciano de OncologíaHospital Universitario Ramón y CajalHospital Clínico Universitario Lozano BlesaVall d’Hebrón University Hospital/Vall d’Hebron Institute of Oncology (VHIO)Complejo Asistencial Universitario de LeónUniversity Hospital St. Joan de ReusSOLTI Breast Cancer Research GroupDepartment of Medical Oncology, Hospital Clínic de BarcelonaDepartment of Medical Oncology, Hospital Clínic de BarcelonaSOLTI Breast Cancer Research GroupSOLTI Breast Cancer Research GroupHospital Universitario 12 de OctubreDepartment of Medical Oncology, Hospital Clínic de BarcelonaAbstract Background The biological effect of oral metronomic vinorelbine (mVNB) alone or in combination with endocrine therapy in patients with hormone receptor-positive (HR+)/HER2-negative breast cancer has been scarcely addressed. Methods Postmenopausal women with untreated stage I–III HR+/HER2-negative breast cancer were randomized (1:1:1) to receive 3 weeks of letrozole (LTZ) 2.5 mg/day, oral mVNB 50 mg 3 days/week, or the combination. The primary objective was to evaluate, within PAM50 Luminal A/B disease, if the anti-proliferative effect of LTZ+mVNB was superior to monotherapy. An anti-proliferative effect was defined as the mean relative decrease of the PAM50 11-gene proliferation score in combination arm vs. both monotherapy arms. Secondary objectives included the evaluation of a comprehensive panel of breast cancer-related genes and safety. An unplanned analysis of stromal tumor-infiltrating lymphocytes (sTILs) was also performed. PAM50 analyses were performed using the nCounter®-based Breast Cancer 360™ gene panel, which includes 752 genes and 32 signatures. Results Sixty-one patients were randomized, and 54 paired samples (89%) were analyzed. The main patient characteristics were mean age of 67, mean tumor size of 1.7 cm, mean Ki67 of 14.3%, stage I (55.7%), and grades 1–2 (90%). Most baseline samples were PAM50 Luminal A (74.1%) or B (22.2%). The anti-proliferative effect of 3 weeks of LTZ+mVNB (− 73.2%) was superior to both monotherapy arms combined (− 49.9%; p = 0.001) and mVNB (− 19.1%; p < 0.001). The anti-proliferative effect of LTZ+mVNB (− 73.2%) was numerically higher compared to LTZ (− 65.7%) but did not reach statistical significance (p = 0.328). LTZ+mVNB induced high expression of immune-related genes and gene signatures, including CD8 T cell signature and PDL1 gene and low expression of ER-regulated genes (e.g., progesterone receptor) and cell cycle-related and DNA repair genes. In tumors with ≤ 10% sTILs at baseline, a statistically significant increase in sTILs was observed following LTZ (paired analysis p = 0.049) and LTZ+mVNB (p = 0.012). Grade 3 adverse events occurred in 3.4% of the cases. Conclusions Short-term mVNB is well-tolerated and presents anti-proliferative activity alone and in combination with LTZ. The high expression of immune-related biological processes and sTILs observed with the combination opens the possibility of studying this combination with immunotherapy. Further investigation comparing these biological results with other metronomic schedules or drug combinations is warranted. Trial registration NCT02802748, registered 16 June 2016.http://link.springer.com/article/10.1186/s13058-019-1195-zBreast cancerMetronomicVinorelbineLetrozoleWindow of opportunityGene expression |
| spellingShingle | Barbara Adamo Meritxell Bellet Laia Paré Tomás Pascual Maria Vidal José A. Pérez Fidalgo Salvador Blanch Noelia Martinez Laura Murillo Patricia Gómez-Pardo Ana López-González Kepa Amillano Jordi Canes Patricia Galván Blanca González-Farré Xavier González Patricia Villagrasa Eva Ciruelos Aleix Prat Oral metronomic vinorelbine combined with endocrine therapy in hormone receptor-positive HER2-negative breast cancer: SOLTI-1501 VENTANA window of opportunity trial Breast Cancer Research Breast cancer Metronomic Vinorelbine Letrozole Window of opportunity Gene expression |
| title | Oral metronomic vinorelbine combined with endocrine therapy in hormone receptor-positive HER2-negative breast cancer: SOLTI-1501 VENTANA window of opportunity trial |
| title_full | Oral metronomic vinorelbine combined with endocrine therapy in hormone receptor-positive HER2-negative breast cancer: SOLTI-1501 VENTANA window of opportunity trial |
| title_fullStr | Oral metronomic vinorelbine combined with endocrine therapy in hormone receptor-positive HER2-negative breast cancer: SOLTI-1501 VENTANA window of opportunity trial |
| title_full_unstemmed | Oral metronomic vinorelbine combined with endocrine therapy in hormone receptor-positive HER2-negative breast cancer: SOLTI-1501 VENTANA window of opportunity trial |
| title_short | Oral metronomic vinorelbine combined with endocrine therapy in hormone receptor-positive HER2-negative breast cancer: SOLTI-1501 VENTANA window of opportunity trial |
| title_sort | oral metronomic vinorelbine combined with endocrine therapy in hormone receptor positive her2 negative breast cancer solti 1501 ventana window of opportunity trial |
| topic | Breast cancer Metronomic Vinorelbine Letrozole Window of opportunity Gene expression |
| url | http://link.springer.com/article/10.1186/s13058-019-1195-z |
| work_keys_str_mv | AT barbaraadamo oralmetronomicvinorelbinecombinedwithendocrinetherapyinhormonereceptorpositiveher2negativebreastcancersolti1501ventanawindowofopportunitytrial AT meritxellbellet oralmetronomicvinorelbinecombinedwithendocrinetherapyinhormonereceptorpositiveher2negativebreastcancersolti1501ventanawindowofopportunitytrial AT laiapare oralmetronomicvinorelbinecombinedwithendocrinetherapyinhormonereceptorpositiveher2negativebreastcancersolti1501ventanawindowofopportunitytrial AT tomaspascual oralmetronomicvinorelbinecombinedwithendocrinetherapyinhormonereceptorpositiveher2negativebreastcancersolti1501ventanawindowofopportunitytrial AT mariavidal oralmetronomicvinorelbinecombinedwithendocrinetherapyinhormonereceptorpositiveher2negativebreastcancersolti1501ventanawindowofopportunitytrial AT joseaperezfidalgo oralmetronomicvinorelbinecombinedwithendocrinetherapyinhormonereceptorpositiveher2negativebreastcancersolti1501ventanawindowofopportunitytrial AT salvadorblanch oralmetronomicvinorelbinecombinedwithendocrinetherapyinhormonereceptorpositiveher2negativebreastcancersolti1501ventanawindowofopportunitytrial AT noeliamartinez oralmetronomicvinorelbinecombinedwithendocrinetherapyinhormonereceptorpositiveher2negativebreastcancersolti1501ventanawindowofopportunitytrial AT lauramurillo oralmetronomicvinorelbinecombinedwithendocrinetherapyinhormonereceptorpositiveher2negativebreastcancersolti1501ventanawindowofopportunitytrial AT patriciagomezpardo oralmetronomicvinorelbinecombinedwithendocrinetherapyinhormonereceptorpositiveher2negativebreastcancersolti1501ventanawindowofopportunitytrial AT analopezgonzalez oralmetronomicvinorelbinecombinedwithendocrinetherapyinhormonereceptorpositiveher2negativebreastcancersolti1501ventanawindowofopportunitytrial AT kepaamillano oralmetronomicvinorelbinecombinedwithendocrinetherapyinhormonereceptorpositiveher2negativebreastcancersolti1501ventanawindowofopportunitytrial AT jordicanes oralmetronomicvinorelbinecombinedwithendocrinetherapyinhormonereceptorpositiveher2negativebreastcancersolti1501ventanawindowofopportunitytrial AT patriciagalvan oralmetronomicvinorelbinecombinedwithendocrinetherapyinhormonereceptorpositiveher2negativebreastcancersolti1501ventanawindowofopportunitytrial AT blancagonzalezfarre oralmetronomicvinorelbinecombinedwithendocrinetherapyinhormonereceptorpositiveher2negativebreastcancersolti1501ventanawindowofopportunitytrial AT xaviergonzalez oralmetronomicvinorelbinecombinedwithendocrinetherapyinhormonereceptorpositiveher2negativebreastcancersolti1501ventanawindowofopportunitytrial AT patriciavillagrasa oralmetronomicvinorelbinecombinedwithendocrinetherapyinhormonereceptorpositiveher2negativebreastcancersolti1501ventanawindowofopportunitytrial AT evaciruelos oralmetronomicvinorelbinecombinedwithendocrinetherapyinhormonereceptorpositiveher2negativebreastcancersolti1501ventanawindowofopportunitytrial AT aleixprat oralmetronomicvinorelbinecombinedwithendocrinetherapyinhormonereceptorpositiveher2negativebreastcancersolti1501ventanawindowofopportunitytrial |