Response-guided neoadjuvant sacituzumab govitecan for localized triple-negative breast cancer : results from the NeoSTAR trial
Copyright © 2023. Published by Elsevier Ltd..
BACKGROUND: Sacituzumab govitecan (SG), a novel antibody-drug conjugate (ADC) targeting TROP2, is approved for pre-treated metastatic triple-negative breast cancer (mTNBC). We conducted an investigator-initiated clinical trial evaluating neoadjuvant (NA) SG (NCT04230109), and report primary results.
PATIENTS AND METHODS: Participants with early-stage TNBC received NA SG for four cycles. The primary objective was to assess pathological complete response (pCR) rate in breast and lymph nodes (ypT0/isN0) to SG. Secondary objectives included overall response rate (ORR), safety, event-free survival (EFS), and predictive biomarkers. A response-guided approach was utilized, and subsequent systemic therapy decisions were at the discretion of the treating physician.
RESULTS: From July 2020 to August 2021, 50 participants were enrolled (median age = 48.5 years; 13 clinical stage I disease, 26 stage II, 11 stage III). Forty-nine (98%) completed four cycles of SG. Overall, the pCR rate with SG alone was 30% [n = 15, 95% confidence interval (CI) 18% to 45%]. The ORR per RECIST V1.1 after SG alone was 64% (n = 32/50, 95% CI 77% to 98%). Higher Ki-67 and tumor-infiltrating lymphocytes (TILs) were predictive of pCR to SG (P = 0.007 for Ki-67 and 0.002 for TILs), while baseline TROP2 expression was not (P = 0.440). Common adverse events were nausea (82%), fatigue (76%), alopecia (76%), neutropenia (44%), and rash (48%). With a median follow-up time of 18.9 months (95% CI 16.3-21.9 months), the 2-year EFS for all participants was 95%. Among participants with a pCR with SG (n = 15), the 2-year EFS was 100%.
CONCLUSIONS: In the first NA trial with an ADC in localized TNBC, SG demonstrated single-agent efficacy and feasibility of response-guided escalation/de-escalation. Further research on optimal duration of SG as well as NA combination strategies, including immunotherapy, are needed.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:35 |
|---|---|
| Enthalten in: |
Annals of oncology : official journal of the European Society for Medical Oncology - 35(2024), 3 vom: 01. Feb., Seite 293-301 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Spring, L M [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 26.02.2024 Date Revised 26.02.2024 published: Print-Electronic ClinicalTrials.gov: NCT04230109 Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.annonc.2023.11.018 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM365829331 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM365829331 | ||
| 003 | DE-627 | ||
| 005 | 20240229154721.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.annonc.2023.11.018 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1306.xml |
| 035 | |a (DE-627)NLM365829331 | ||
| 035 | |a (NLM)38092228 | ||
| 035 | |a (PII)S0923-7534(23)05107-4 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Spring, L M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Response-guided neoadjuvant sacituzumab govitecan for localized triple-negative breast cancer |b results from the NeoSTAR trial |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 26.02.2024 | ||
| 500 | |a Date Revised 26.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT04230109 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023. Published by Elsevier Ltd. | ||
| 520 | |a BACKGROUND: Sacituzumab govitecan (SG), a novel antibody-drug conjugate (ADC) targeting TROP2, is approved for pre-treated metastatic triple-negative breast cancer (mTNBC). We conducted an investigator-initiated clinical trial evaluating neoadjuvant (NA) SG (NCT04230109), and report primary results | ||
| 520 | |a PATIENTS AND METHODS: Participants with early-stage TNBC received NA SG for four cycles. The primary objective was to assess pathological complete response (pCR) rate in breast and lymph nodes (ypT0/isN0) to SG. Secondary objectives included overall response rate (ORR), safety, event-free survival (EFS), and predictive biomarkers. A response-guided approach was utilized, and subsequent systemic therapy decisions were at the discretion of the treating physician | ||
| 520 | |a RESULTS: From July 2020 to August 2021, 50 participants were enrolled (median age = 48.5 years; 13 clinical stage I disease, 26 stage II, 11 stage III). Forty-nine (98%) completed four cycles of SG. Overall, the pCR rate with SG alone was 30% [n = 15, 95% confidence interval (CI) 18% to 45%]. The ORR per RECIST V1.1 after SG alone was 64% (n = 32/50, 95% CI 77% to 98%). Higher Ki-67 and tumor-infiltrating lymphocytes (TILs) were predictive of pCR to SG (P = 0.007 for Ki-67 and 0.002 for TILs), while baseline TROP2 expression was not (P = 0.440). Common adverse events were nausea (82%), fatigue (76%), alopecia (76%), neutropenia (44%), and rash (48%). With a median follow-up time of 18.9 months (95% CI 16.3-21.9 months), the 2-year EFS for all participants was 95%. Among participants with a pCR with SG (n = 15), the 2-year EFS was 100% | ||
| 520 | |a CONCLUSIONS: In the first NA trial with an ADC in localized TNBC, SG demonstrated single-agent efficacy and feasibility of response-guided escalation/de-escalation. Further research on optimal duration of SG as well as NA combination strategies, including immunotherapy, are needed | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ADC | |
| 650 | 4 | |a TROP2 | |
| 650 | 4 | |a neoadjuvant | |
| 650 | 4 | |a sacituzumab govitecan | |
| 650 | 4 | |a triple-negative breast cancer | |
| 650 | 7 | |a sacituzumab govitecan |2 NLM | |
| 650 | 7 | |a M9BYU8XDQ6 |2 NLM | |
| 650 | 7 | |a Ki-67 Antigen |2 NLM | |
| 650 | 7 | |a Antigens, Neoplasm |2 NLM | |
| 650 | 7 | |a Camptothecin |2 NLM | |
| 650 | 7 | |a XT3Z54Z28A |2 NLM | |
| 650 | 7 | |a Immunoconjugates |2 NLM | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 700 | 1 | |a Tolaney, S M |e verfasserin |4 aut | |
| 700 | 1 | |a Fell, G |e verfasserin |4 aut | |
| 700 | 1 | |a Bossuyt, V |e verfasserin |4 aut | |
| 700 | 1 | |a Abelman, R O |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, B |e verfasserin |4 aut | |
| 700 | 1 | |a Maheswaran, S |e verfasserin |4 aut | |
| 700 | 1 | |a Trippa, L |e verfasserin |4 aut | |
| 700 | 1 | |a Comander, A |e verfasserin |4 aut | |
| 700 | 1 | |a Mulvey, T |e verfasserin |4 aut | |
| 700 | 1 | |a McLaughlin, S |e verfasserin |4 aut | |
| 700 | 1 | |a Ryan, P |e verfasserin |4 aut | |
| 700 | 1 | |a Ryan, L |e verfasserin |4 aut | |
| 700 | 1 | |a Abraham, E |e verfasserin |4 aut | |
| 700 | 1 | |a Rosenstock, A |e verfasserin |4 aut | |
| 700 | 1 | |a Garrido-Castro, A C |e verfasserin |4 aut | |
| 700 | 1 | |a Lynce, F |e verfasserin |4 aut | |
| 700 | 1 | |a Moy, B |e verfasserin |4 aut | |
| 700 | 1 | |a Isakoff, S J |e verfasserin |4 aut | |
| 700 | 1 | |a Tung, N |e verfasserin |4 aut | |
| 700 | 1 | |a Mittendorf, E A |e verfasserin |4 aut | |
| 700 | 1 | |a Ellisen, L W |e verfasserin |4 aut | |
| 700 | 1 | |a Bardia, A |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Annals of oncology : official journal of the European Society for Medical Oncology |d 1990 |g 35(2024), 3 vom: 01. Feb., Seite 293-301 |w (DE-627)NLM012606308 |x 1569-8041 |7 nnns |
| 773 | 1 | 8 | |g volume:35 |g year:2024 |g number:3 |g day:01 |g month:02 |g pages:293-301 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.annonc.2023.11.018 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 35 |j 2024 |e 3 |b 01 |c 02 |h 293-301 | ||