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http://hdl.handle.net/2445/174106
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DC Field | Value | Language |
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dc.contributor.author | Barroso Sousa, Romualdo | - |
dc.contributor.author | Keenan, Tanya E. | - |
dc.contributor.author | Pernas, Sònia | - |
dc.contributor.author | Exman, Pedro | - |
dc.contributor.author | Jain, Esha | - |
dc.contributor.author | Garrido Castro, Ana C. | - |
dc.contributor.author | Hughes, Melissa | - |
dc.contributor.author | Bychkovsky, Brittany | - |
dc.contributor.author | Umeton, Renato | - |
dc.contributor.author | Files, Janet L. | - |
dc.contributor.author | Lindeman, Neal I. | - |
dc.contributor.author | MacConaill, Laura E. | - |
dc.contributor.author | Hodi, F. Stephen | - |
dc.contributor.author | Krop, Ian E. | - |
dc.contributor.author | Dillon, Deborah | - |
dc.contributor.author | Winer, Eric P. | - |
dc.contributor.author | Wagle, Nikhil | - |
dc.contributor.author | Lin, Nancy U. | - |
dc.contributor.author | Mittendorf, Elizabeth A. | - |
dc.contributor.author | Van Allen, Eliezer M. | - |
dc.contributor.author | Tolaney, Sara M. | - |
dc.date.accessioned | 2021-02-22T09:03:03Z | - |
dc.date.available | 2021-02-22T09:03:03Z | - |
dc.date.issued | 2020-02-04 | - |
dc.identifier.uri | http://hdl.handle.net/2445/174106 | - |
dc.description.abstract | Purpose: Few patients with metastatic triple-negative breast cancer (mTNBC) benefit from immune checkpoint inhibitors (ICI). On the basis of immunotherapy response correlates in other cancers, we evaluated whether high tumor mutational burden (TMB) ≥10 nonsynonymous mutations/megabase and PTEN alterations, defined as nonsynonymous mutations or 1 or 2 copy deletions, were associated with clinical benefit to anti-PD-1/L1 therapy in mTNBC. Experimental design: We identified patients with mTNBC, who consented to targeted DNA sequencing and were treated with ICIs on clinical trials between April 2014 and January 2019 at Dana-Farber Cancer Institute (Boston, MA). Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were correlated with tumor genomic features. Results: Sixty-two women received anti-PD-1/L1 inhibitors alone (23%) or combined with targeted therapy (19%) or chemotherapy (58%). High TMB (18%) was associated with significantly longer PFS (12.5 vs. 3.7 months; P = 0.04), while PTEN alterations (29%) were associated with significantly lower ORR (6% vs. 48%; P = 0.01), shorter PFS (2.3 vs. 6.1 months; P = 0.01), and shorter OS (9.7 vs. 20.5 months; P = 0.02). Multivariate analyses confirmed that these associations were independent of performance status, prior lines of therapy, therapy regimen, and visceral metastases. The survival associations were additionally independent of PD-L1 in patients with known PD-L1 and were not found in mTNBC cohorts treated with chemotherapy (n = 90) and non-ICI regimens (n = 169). Conclusions: Among patients with mTNBC treated with anti-PD-1/L1 therapies, high TMB and PTEN alterations were associated with longer and shorter survival, respectively. These observations warrant validation in larger datasets. | - |
dc.format.extent | 16 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | American Association for Cancer Research (AACR) | - |
dc.relation.isformatof | Versió postprint del document publicat a: https://doi.org/10.1158/1078-0432.CCR-19-3507 | - |
dc.relation.ispartof | Clinical Cancer Research, 2020, vol. 26, issue. 11, p. 2565-2572 | - |
dc.relation.uri | https://doi.org/10.1158/1078-0432.CCR-19-3507 | - |
dc.rights | (c) American Association for Cancer Research, 2020 | - |
dc.source | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) | - |
dc.subject.classification | Càncer de mama | - |
dc.subject.classification | Immunoteràpia | - |
dc.subject.other | Breast cancer | - |
dc.subject.other | Immunotherapy | - |
dc.title | Tumor mutational burden and PTEN alterations as molecular correlates of response to PD-1/L1 blockade in metastatic triple-negative breast cancer | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/AcceptedVersion | - |
dc.date.updated | 2021-02-19T13:59:43Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 32019858 | - |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
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nihms-1557408.pdf | 358.51 kB | Adobe PDF | View/Open |
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