Details

Autor(en) / Beteiligte

• Pusztai, Lajos
• Yau, Christina
• Wolf, Denise M.
• Han, Hyo S.
• Du, Lili
• Wallace, Anne M.
• String-Reasor, Erica
• Boughey, Judy C.
• Chien, A. Jo
• Elias, Anthony D.
• Beckwith, Heather
• Nanda, Rita
• Albain, Kathy S.
• Clark, Amy S.
• Kemmer, Kathleen
• Kalinsky, Kevin
• Isaacs, Claudine
• Thomas, Alexandra
• Shatsky, Rebecca
• Helsten, Theresa L.
• Forero-Torres, Andres
• Liu, Minetta C.
• Brown-Swigart, Lamorna
• Petricoin, Emmanuel F.
• Wulfkuhle, Julia D.
• Asare, Smita M.
• Wilson, Amy
• Singhrao, Ruby
• Sit, Laura
• Hirst, Gillian L.
• Berry, Scott
• Sanil, Ashish
• Asare, Adam L.
• Matthews, Jeffrey B.
• Perlmutter, Jane
• Melisko, Michelle
• Rugo, Hope S.
• Schwab, Richard B.
• Symmans, W. Fraser
• Yee, Doug
• van’t Veer, Laura J.
• Hylton, Nola M.
• DeMichele, Angela M.
• Berry, Donald A.
• Esserman, Laura J.

Titel

Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial

Ist Teil von

• Cancer cell, 2021-07, Vol.39 (7), p.989-998.e5

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• The combination of PD-L1 inhibitor durvalumab and PARP inhibitor olaparib added to standard paclitaxel neoadjuvant chemotherapy (durvalumab/olaparib/paclitaxel [DOP]) was investigated in the phase II I-SPY2 trial of stage II/III HER2-negative breast cancer. Seventy-three participants were randomized to DOP and 299 to standard of care (paclitaxel) control. DOP increased pathologic complete response (pCR) rates in all HER2-negative (20%–37%), hormone receptor (HR)-positive/HER2-negative (14%–28%), and triple-negative breast cancer (TNBC) (27%–47%). In HR-positive/HER2-negative cancers, MammaPrint ultra-high (MP2) cases benefited selectively from DOP (pCR 64% versus 22%), no benefit was seen in MP1 cancers (pCR 9% versus 10%). Overall, 12.3% of patients in the DOP arm experienced immune-related grade 3 adverse events versus 1.3% in control. Gene expression signatures associated with immune response were positively associated with pCR in both arms, while a mast cell signature was associated with non-pCR. DOP has superior efficacy over standard neoadjuvant chemotherapy in HER2-negative breast cancer, particularly in a highly sensitive subset of high-risk HR-positive/HER2-negative patients. [Display omitted] •Durvalumab plus olaparib improved chemotherapy efficacy in HER2-negative breast cancer•Immune-rich tumors had greater sensitivity to therapy•Among ER+ cancer, only Mammaprint MP2 cancers benefited from immune checkpoint therapy Pusztai et al. report findings from the I-SPY2 trial showing durvalumab and olaparib administered with paclitaxel improved pathologic complete response (pCR) rate in HER2-negative breast cancers, including TNBC and ER-positive cancers. Among the ER-positive/HER2-negative cancers, only the highly proliferative, estrogen receptor low, MammaPrint MP2 subset benefited from the combination therapy.