A randomized phase 2 study of neoadjuvant carboplatin and paclitaxel with or without atezolizumab in triple negative breast cancer (TNBC)-NCI 10013

被引：26

作者：

Ademuyiwa, Foluso O. ^{[1
]}

Gao, Feng ^{[1
]}

Street, Cherease R. ^{[1
]}

Chen, Ina ^{[1
]}

Northfelt, Donald W. ^{[2
]}

Wesolowski, Robert ^{[3
]}

Arora, Mili ^{[4
]}

Brufsky, Adam ^{[5
]}

Dees, E. Claire ^{[6
]}

Santa-Maria, Cesar A. ^{[7
]}

Connolly, Roisin M. ^{[8
]}

Force, Jeremy ^{[9
]}

Moreno-Aspitia, Alvaro ^{[10
]}

Herndon, John M. ^{[1
]}

Carmody, Madelyn ^{[1
]}

Davies, Sherri R. ^{[1
]}

Larson, Sarah ^{[1
]}

Pfaff, Kathleen L. ^{[11
]}

Jones, Stephanie M. ^{[11
]}

Weirather, Jason L. ^{[11
]}

Giobbie-Hurder, Anita ^{[11
]}

Rodig, Scott J. ^{[11
]}

Liu, Zheng ^{[1
]}

Hagemann, Ian S. ^{[1
]}

Sharon, Elad ^{[12
]}

Gillanders, William E. ^{[1
]}

机构：

[1] Washington Univ, Sch Med, St Louis, MO 63110 USA

[2] Mayo Clin, Phoenix, AZ 85054 USA

[3] Ohio State Univ, Comprehens Canc Ctr, Columbus, OH 43210 USA

[4] Univ Calif Davis, Comprehens Canc Ctr, Sacramento, CA 95817 USA

[5] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA

[6] Univ N Carolina, Sch Med, Chapel Hill, NC 27514 USA

[7] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21287 USA

[8] Univ Coll Cork, Cork, Ireland

[9] Duke Univ, Sch Med, Durham, NC 27710 USA

[10] Mayo Clin, Jacksonville, FL 32224 USA

[11] Dana Farber Canc Inst, Canc Immune Monitoring & Anal Ctr, Boston, MA 02215 USA

[12] NCI, Bethesda, MD 20892 USA

来源：

NPJ BREAST CANCER | 2022年 / 8卷 / 01期

基金：

美国国家卫生研究院;

关键词：

TUMOR-INFILTRATING LYMPHOCYTES; ANTHRACYCLINE-FREE CHEMOTHERAPY; PATHOLOGICAL COMPLETE RESPONSE; LIGAND; MULTICENTRIC ANALYSIS; CLINICAL-FEATURES; POOR-PROGNOSIS; HIGH-RISK; EXPRESSION; DOCETAXEL;

D O I：

10.1038/s41523-022-00500-3

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Atezolizumab with chemotherapy has shown improved progression-free and overall survival in patients with metastatic PD-L1 positive triple negative breast cancer (TNBC). Atezolizumab with anthracycline- and taxane-based neoadjuvant chemotherapy has also shown increased pathological complete response (pCR) rates in early TNBC. This trial evaluated neoadjuvant carboplatin and paclitaxel with or without atezolizumab in patients with clinical stages II-III TNBC. The co-primary objectives were to evaluate if chemotherapy and atezolizumab increase pCR rate and tumor infiltrating lymphocyte (TIL) percentage compared to chemotherapy alone in the mITT population. Sixty-seven patients (ages 25-78 years; median, 52 years) were randomly assigned - 22 patients to Arm A, and 45 to Arm B. Median follow up was 6.6 months. In the modified intent to treat population (all patients evaluable for the primary endpoints who received at least one dose of combination therapy), the pCR rate was 18.8% (95% CI 4.0-45.6%) in Arm A, and 55.6% (95% CI 40.0-70.4%) in Arm B (estimated treatment difference: 36.8%, 95% CI 8.5-56.6%; p = 0.018). Grade 3 or higher treatment-related adverse events occurred in 62.5% of patients in Arm A, and 57.8% of patients in Arm B. One patient in Arm B died from recurrent disease during the follow-up period. TIL percentage increased slightly from baseline to cycle 1 in both Arm A (mean & PLUSMN; SD: 0.6% & PLUSMN; 21.0%) and Arm B (5.7% & PLUSMN; 15.8%) (p = 0.36). Patients with pCR had higher median TIL percentages (24.8%) than those with non-pCR (14.2%) (p = 0.02). Although subgroup analyses were limited by the small sample size, PD-L1-positive patients treated with chemotherapy and atezolizumab had a pCR rate of 75% (12/16). The addition of atezolizumab to neoadjuvant carboplatin and paclitaxel resulted in a statistically significant and clinically relevant increased pCR rate in patients with clinical stages II and III TNBC. (Funded by National Cancer Institute).

引用

页数：11

共 58 条

[1] Prognostic Value of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancers From Two Phase III Randomized Adjuvant Breast Cancer Trials: ECOG 2197 and ECOG 1199 [J].

Adams, Sylvia ;

Gray, Robert J. ;

Demaria, Sandra ;

Goldstein, Lori ;

Perez, Edith A. ;

Shulman, Lawrence N. ;

Martino, Silvana ;

Wang, Molin ;

Jones, Vicky E. ;

Saphner, Thomas J. ;

Wolff, Antonio C. ;

Wood, William C. ;

Davidson, Nancy E. ;

Sledge, George W. ;

Sparano, Joseph A. ;

Badve, Sunil S. .

JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (27) :2959-+

[2] Immunogenomic profiling and pathological response results from a clinical trial of docetaxel and carboplatin in triple-negative breast cancer [J].

Ademuyiwa, Foluso O. ;

Chen, Ina ;

Luo, Jingqin ;

Rimawi, Mothaffar F. ;

Hagemann, Ian S. ;

Fisk, Bryan ;

Jeffers, Gejae ;

Skidmore, Zachary L. ;

Basu, Anamika ;

Richters, Megan ;

Ma, Cynthia X. ;

Weilbaecher, Katherine ;

Davis, Jennifer ;

Suresh, Rama ;

Peterson, Lindsay L. ;

Bose, Ron ;

Bagegni, Nusayba ;

Rigden, Caron E. ;

Frith, Ashley ;

Rearden, Timothy P. ;

Hernandez-Aya, Leonel F. ;

Roshal, Anna ;

Clifton, Katherine ;

Opyrchal, Mateusz ;

Akintola-Ogunremi, Olaronke ;

Lee, Byung Ha ;

Ferrando-Martinez, Sara ;

Church, Sarah E. ;

Anurag, Meenakshi ;

Ellis, Matthew J. ;

Gao, Feng ;

Gillanders, William ;

Griffith, Obi L. ;

Griffith, Malachi .

BREAST CANCER RESEARCH AND TREATMENT, 2021, 189 (01) :187-202

[3] Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100 000 women in 123 randomised trials [J].

Albain, K. ;

Anderson, S. ;

Arriagada, R. ;

Barlow, W. ;

Bergh, J. ;

Bliss, J. ;

Buyse, M. ;

Cameron, D. ;

Carrasco, E. ;

Clarke, M. ;

Correa, C. ;

Coates, A. ;

Collins, R. ;

Costantino, J. ;

Cutter, D. ;

Cuzick, J. ;

Darby, S. ;

Davidson, N. ;

Davies, C. ;

Davies, K. ;

Delmestri, A. ;

Di Leo, A. ;

Dowsett, M. ;

Elphinstone, P. ;

Evans, V. ;

Ewertz, M. ;

Gelber, R. ;

Gettins, L. ;

Geyer, C. ;

Goldhirsch, A. ;

Godwin, J. ;

Gray, R. ;

Gregory, C. ;

Hayes, D. ;

Hill, C. ;

Ingle, J. ;

Jakesz, R. ;

James, S. ;

Kaufmann, M. ;

Kerr, A. ;

MacKinnon, E. ;

McGale, P. ;

McHugh, T. ;

Norton, L. ;

Ohashi, Y. ;

Paik, S. ;

Pan, H. C. ;

Perez, E. ;

Peto, R. ;

Piccart, M. .

LANCET, 2012, 379 (9814) :432-444

[4] Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial [J].

Balar, Arjun V. ;

Galsky, Matthew D. ;

Rosenberg, Jonathan E. ;

Powles, Thomas ;

Petrylak, Daniel P. ;

Bellmunt, Joaquim ;

Loriot, Yohann ;

Necchi, Andrea ;

Hoffman-Censits, Jean ;

Perez-Gracia, Jose Luis ;

Dawson, Nancy A. ;

van der Heijden, Michiel S. ;

Dreicer, Robert ;

Srinivas, Sandy ;

Retz, Margitta M. ;

Joseph, Richard W. ;

Drakaki, Alexandra ;

Vaishampayan, Ulka N. ;

Sridhar, Srikala S. ;

Quinn, David I. ;

Duran, Ignacio ;

Shaffer, David R. ;

Eigl, Bernhard J. ;

Grivas, Petros D. ;

Yu, Evan Y. ;

Li, Shi ;

Kadel, Edward E., III ;

Boyd, Zachary ;

Bourgon, Richard ;

Hegde, Priti S. ;

Mariathasan, Sanjeev ;

Thastrom, AnnChristine ;

Abidoye, Oyewale O. ;

Fine, Gregg D. ;

Bajorin, Dean F. .

LANCET, 2017, 389 (10064) :67-76

[5] Programmed death ligand 1 expression in triple-negative breast cancer is associated with tumour-infiltrating lymphocytes and improved outcome [J].

Beckers, Rhiannon K. ;

Selinger, Christina I. ;

Vilain, Ricardo ;

Madore, Jason ;

Wilmott, James S. ;

Harvey, Kate ;

Holliday, Anne ;

Cooper, Caroline L. ;

Robbins, Elizabeth ;

Gillett, David ;

Kennedy, Catherine W. ;

Gluch, Laurence ;

Carmalt, Hugh ;

Mak, Cindy ;

Warrier, Sanjay ;

Gee, Harriet E. ;

Chan, Charles ;

McLean, Anna ;

Walker, Emily ;

McNeil, Catriona M. ;

Beith, Jane M. ;

Swarbrick, Alexander ;

Scolyer, Richard A. ;

O'Toole, Sandra A. .

HISTOPATHOLOGY, 2016, 69 (01) :25-34

[6] Interaction of PD-L1 on tumor cells with PD-1 on tumor-specific T cells as a mechanism of immune evasion: implications for tumor immunotherapy [J].

Blank, C ;

Gajewski, TF ;

Mackensen, A .

CANCER IMMUNOLOGY IMMUNOTHERAPY, 2005, 54 (04) :307-314

[7] Contribution of the PD-L1/PD-1 pathway to T-cell exhaustion: an update on implications for chronic infections and tumor evasion [J].

Blank, Christian ;

Mackensen, Andreas .

CANCER IMMUNOLOGY IMMUNOTHERAPY, 2007, 56 (05) :739-745

[8] Classical pathology and mutational load of breast cancer - integration of two worlds [J].

Budczies, Jan ;

Bockmayr, Michael ;

Denkert, Carsten ;

Klauschen, Frederick ;

Lennerz, Jochen K. ;

Gyorffy, Balazs ;

Dietel, Manfred ;

Loibl, Sibylle ;

Weichert, Wilko ;

Stenzinger, Albrecht .

JOURNAL OF PATHOLOGY CLINICAL RESEARCH, 2015, 1 (04) :225-238

[9] Cancer immunotherapy - immune checkpoint blockade and associated endocrinopathies [J].

Byun, David J. ;

Wolchok, Jedd D. ;

Rosenberg, Lynne M. ;

Girotra, Monica .

NATURE REVIEWS ENDOCRINOLOGY, 2017, 13 (04) :195-207

[10] Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy With or Without Carboplatin in Human Epidermal Growth Factor Receptor 2-Positive and Triple-Negative Primary Breast Cancers [J].

Denkert, Carsten ;

von Minckwitz, Gunter ;

Brase, Jan C. ;

Sinn, Bruno V. ;

Gade, Stephan ;

Kronenwett, Ralf ;

Pfitzner, Berit M. ;

Salat, Christoph ;

Loi, Sherene ;

Schmitt, Wolfgang D. ;

Schem, Christian ;

Fisch, Karin ;

Darb-Esfahani, Silvia ;

Mehta, Keyur ;

Sotiriou, Christos ;

Wienert, Stephan ;

Klare, Peter ;

Andre, Fabrice ;

Klauschen, Frederick ;

Blohmer, Jens-Uwe ;

Krappmann, Kristin ;

Schmidt, Marcus ;

Tesch, Hans ;

Kuemmel, Sherko ;

Sinn, Peter ;

Jackisch, Christian ;

Dietel, Manfred ;

Reimer, Toralf ;

Untch, Michael ;

Loibl, Sibylle .

JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (09) :983-991

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