Neoadjuvant atezolizumab for resectable non-small cell lung cancer: an open-label, single-arm phase II trial

被引：185

作者：

Chaft, Jamie E. ^{[1
,2
]}

Oezkan, Filiz ^{[3
,4
,5
,6
]}

Kris, Mark G. ^{[1
,2
]}

Bunn, Paul A. ^{[7
]}

Wistuba, Ignacio I. ^{[8
]}

Kwiatkowski, David J. ^{[9
,10
]}

Owen, Dwight H. ^{[3
,11
]}

Tang, Yan ^{[10
]}

Johnson, Bruce E. ^{[9
,10
]}

Lee, Jay M. ^{[12
]}

Lozanski, Gerard ^{[11
]}

Pietrzak, Maciej ^{[11
]}

Seweryn, Michal ^{[11
,13
,14
]}

Byun, Woo Yul ^{[11
]}

Schulze, Katja ^{[15
]}

Nicholas, Alan ^{[15
]}

Johnson, Ann ^{[15
]}

Grindheim, Jessica ^{[15
]}

Hilz, Stephanie ^{[15
]}

Shames, David S. ^{[15
]}

Rivard, Chris ^{[7
]}

Toloza, Eric ^{[16
]}

Haura, Eric B. ^{[16
]}

McNamee, Ciaran J. ^{[9
,10
]}

Patterson, G. Alexander ^{[17
]}

Waqar, Saiama N. ^{[17
]}

Rusch, Valerie W. ^{[1
]}

Carbone, David P. ^{[3
,18
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA

[2] Weill Cornell Med Coll, New York, NY USA

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

[4] Univ Med Essen, Univ Duisburg Essen, Dept Intervent Pulmonol, Ruhrlandklin, Essen, Germany

[5] German Canc Res Ctr, A420, Heidelberg, Germany

[6] Univ Med Mannheim, Fac Univ Heidelberg, Sect Pulmonol, Med Dept 5, Mannheim, Germany

[7] Univ Colorado, Sch Med, Aurora, CO USA

[8] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[9] Dana Farber Canc Inst, Boston, MA 02115 USA

[10] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA

[11] Ohio State Univ, Wexner Med Ctr, Columbus, OH 43210 USA

[12] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA

[13] Univ Lodz, Dept Mol Biophys, Biobank Lab, Lodz, Poland

[14] Univ Lodz, Ctr Data Anal Modeling & Computat Sci, Lodz, Poland

[15] Genentech Inc, San Francisco, CA 94080 USA

[16] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA

[17] Washington Univ, Sch Med, St Louis, MO USA

[18] Pelotonia Inst Immunooncol, Columbus, OH 43210 USA

来源：

NATURE MEDICINE | 2022年 / 28卷 / 10期

关键词：

PATHOLOGICAL RESPONSE; HLA-E; CHEMOTHERAPY; MULTICENTER; BLOCKADE; CRITERIA; COMPLEX;

D O I：

10.1038/s41591-022-01962-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In an ongoing, open-label, single-arm phase II study (NCT02927301), 181 patients with untreated, resectable, stage IB-IIIB non-small cell lung cancer received two doses of neoadjuvant atezolizumab monotherapy. The primary end point was major pathological response (MPR; <= 10% viable malignant cells) in resected tumors without EGFR or ALK alterations. Of the 143 patients in the primary end point analysis, the MPR was 20% (95% confidence interval, 14-28%). With a minimum duration of follow-up of 3 years, the 3-year survival rate of 80% was encouraging. The most common adverse events during the neoadjuvant phase were fatigue (39%, 71 of 181) and procedural pain (29%, 53 of 181), along with expected immune-related toxicities; there were no unexpected safety signals. In exploratory analyses, MPR was predicted using the pre-treatment peripheral blood immunophenotype based on 14 immune cell subsets. Immune cell subsets predictive of MPR in the peripheral blood were also identified in the tumor microenvironment and were associated with MPR. This study of neoadjuvant atezolizumab in a large cohort of patients with resectable non-small cell lung cancer was safe and met its primary end point of MPR >= 15%. Data from this single-arm, non-randomized trial suggest that profiles of innate immune cells in pre-treatment peripheral blood may predict pathological response after neoadjuvant atezolizumab, but additional studies are needed to determine whether these profiles can inform patient selection and new therapeutic approaches.

引用

页码：2155 / +

页数：25

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