Efficacy and clinicogenomic correlates of response to immune checkpoint inhibitors alone or with chemotherapy in non-small cell lung cancer

被引：37

作者：

Hong, Lingzhi ^{[1
,2
]}

Aminu, Muhammad ^{[2
]}

Li, Shenduo ^{[3
]}

Lu, Xuetao ^{[4
]}

Petranovic, Milena ^{[5
]}

Saad, Maliazurina B. ^{[2
]}

Chen, Pingjun ^{[2
]}

Qin, Kang ^{[1
]}

Varghese, Susan ^{[1
]}

Rinsurongkawong, Waree ^{[4
]}

Rinsurongkawong, Vadeerat ^{[4
]}

Spelman, Amy ^{[1
]}

Elamin, Yasir Y. ^{[1
]}

Negrao, Marcelo V. ^{[1
]}

Skoulidis, Ferdinandos ^{[1
]}

Gay, Carl M. ^{[1
]}

Cascone, Tina ^{[1
]}

Gandhi, Saumil J. ^{[6
]}

Lin, Steven H. ^{[6
]}

Lee, Percy P. ^{[6
]}

Carter, Brett W. ^{[7
]}

Wu, Carol C. ^{[7
]}

Antonoff, Mara B. ^{[8
]}

Sepesi, Boris ^{[8
]}

Lewis, Jeff ^{[4
]}

Gibbons, Don L. ^{[1
]}

Vaporciyan, Ara A. ^{[8
]}

Le, Xiuning ^{[1
]}

Jack Lee, J. ^{[4
]}

Roy-Chowdhuri, Sinchita ^{[9
]}

Routbort, Mark J. ^{[9
]}

Gainor, Justin F. ^{[10
]}

Heymach, John V. ^{[1
]}

Lou, Yanyan ^{[3
]}

Wu, Jia ^{[1
,2
]}

Zhang, Jianjun ^{[1
,11
]}

Vokes, Natalie I. ^{[1
,11
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Imaging Phys, Houston, TX USA

[3] Mayo Clin, Div Hematol & Oncol, Jacksonville, FL USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX USA

[5] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Thorac Imaging, Houston, TX USA

[8] Univ Texas MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Houston, TX USA

[9] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX USA

[10] Massachusetts Gen Hosp, Dept Med, Boston, MA USA

[11] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA

来源：

NATURE COMMUNICATIONS | 2023年 / 14卷 / 01期

关键词：

OPEN-LABEL; NIVOLUMAB; DOCETAXEL; PEMBROLIZUMAB; COMBINATION; PHASE-3; NSCLC;

D O I：

10.1038/s41467-023-36328-z

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Immune checkpoint inhibitors with or without chemotherapy are now standard of care for non-small cell lung cancer. However, the benefits of combination vs sequential therapy have not been fully explored. Here, the authors analysed 1,133 patient records and show combination therapy showed increased protection against early progression, but similar overall survival. The role of combination chemotherapy with immune checkpoint inhibitors (ICI) (ICI-chemo) over ICI monotherapy (ICI-mono) in non-small cell lung cancer (NSCLC) remains underexplored. In this retrospective study of 1133 NSCLC patients, treatment with ICI-mono vs ICI-chemo associate with higher rates of early progression, but similar long-term progression-free and overall survival. Sequential vs concurrent ICI and chemotherapy have similar long-term survival, suggesting no synergism from combination therapy. Integrative modeling identified PD-L1, disease burden (Stage IVb; liver metastases), and STK11 and JAK2 alterations as features associate with a higher likelihood of early progression on ICI-mono. CDKN2A alterations associate with worse long-term outcomes in ICI-chemo patients. These results are validated in independent external (n = 89) and internal (n = 393) cohorts. This real-world study suggests that ICI-chemo may protect against early progression but does not influence overall survival, and nominates features that identify those patients at risk for early progression who may maximally benefit from ICI-chemo.

引用

页数：15

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