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Advanced non-small-cell lung cancer treated with first-line pembrolizumab plus chemotherapy: tumor response dynamics as a marker for survival

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Abstract

Objectives

The study investigated tumor burden dynamics on computed tomography (CT) scans in patients with advanced non-small-cell lung cancer (NSCLC) during first-line pembrolizumab plus chemotherapy, to provide imaging markers for overall survival (OS).

Methods

The study included 133 patients treated with first-line pembrolizumab plus platinum-doublet chemotherapy. Serial CT scans during therapy were assessed for tumor burden dynamics during therapy, which were studied for the association with OS.

Results

There were 67 responders, with overall response rate of 50%. The tumor burden change at the best overall response ranged from − 100.0% to + 132.1% (median of − 30%). Higher response rates were associated with younger age (p < 0.001) and higher programmed cell death-1 (PD-L1) expression levels (p = 0.01). Eighty-three patients (62%) showed tumor burden below the baseline burden throughout therapy. Using an 8-week landmark analysis, OS was longer in patients with tumor burden below the baseline burden in the first 8 weeks than in those who experienced ≥ 0% increase (median OS: 26.8 vs. 7.6 months, hazard ratio (HR): 0.36, p < 0.001). Tumor burden remained below their baseline throughout therapy was associated with significantly reduced hazards of death (HR: 0.72, p = 0.03) in the extended Cox models, after adjusting for other clinical variables. Pseudoprogression was noted in only one patient (0.8%).

Conclusions

Tumor burden staying below the baseline burden throughout the therapy was predictive of prolonged overall survival in patients with advanced NSCLC treated with first-line pembrolizumab plus chemotherapy, and may be used as a practical marker for therapeutic decisions in this widely used combination regimen.

Clinical relevance statement

The analysis of tumor burden dynamics on serial CT scans in reference to the baseline burden can provide an additional objective guide for treatment decision making in patients treated with first-line pembrolizumab plus chemotherapy for their advanced NSCLC.

Key Points

• Tumor burden remaining below baseline burden during therapy predicted longer survival during first-line pembrolizumab plus chemotherapy.

• Pseudoprogression was noted in 0.8%, demonstrating the rarity of the phenomenon.

• Tumor burden dynamics may serve as an objective marker for treatment benefit to guide treatment decisions during first-line pembrolizumab plus chemotherapy.

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Abbreviations

BOR:

Best overall response

CR:

Complete response

CT:

Computed tomography

CT:

Computed tomography

ECOG:

Eastern Cooperative Oncology Group

HR:

Hazard ratio

ICI:

Immune-checkpoint inhibitors (ICI)

MRI:

Magnetic resonance imaging

NSCLC:

Non-small-cell lung cancer

OS:

Overall survival

PD:

Progressive disease

PD-1:

Programmed cell death-1

PD-L1:

Programmed cell death-ligand 1

PET:

Positron emission tomography

PR:

Partial response

PS:

Performance status

RECIST:

Response Evaluation Criteria in Solid Tumors

TMB:

Tumor mutational burden

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Funding

This study has received funding by R01CA203636 and U01CA209414.

Author information

Authors and Affiliations

  1. Department of Radiology, Brigham and Women’s Hospital and Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave., MA, 02215, Boston, USA

    Mizuki Nishino, Shu-Chi Tseng, Hyesun Park & Hiroto Hatabu

  2. Department of Environmental Health, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA

    Xinan Wang & David C. Christiani

  3. Department of Medical Oncology and Department of Medicine, Dana-Farber Cancer Institute and Brigham and Women’s Hospital, 450 Brookline Ave., Boston, MA, 02215, USA

    Biagio Ricciuti, Joao V. Alessi, Victor R. Vaz & Mark M. Awad

  4. Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Taoyuan, Taiwan

    Shu-Chi Tseng

  5. Department of Biostatistics, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA

    Xihong Lin

  6. Pulmonary and Critical Care Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, 02115, USA

    David C. Christiani

Authors
  1. Mizuki Nishino
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  2. Xinan Wang
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  4. Shu-Chi Tseng
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  7. Victor R. Vaz
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  8. Hiroto Hatabu
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  11. Mark M. Awad
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Corresponding author

Correspondence to Mizuki Nishino.

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Guarantor

The scientific guarantor of this publication is Mizuki Nishino, MD MPH.

Conflict of interest

Nishino: consultant to Daiichi Sankyo, AstraZeneca; research grant from Merck, Canon Medical Systems, AstraZeneca, Daiichi Sankyo.

Tseng, Alessi, Wang, Park, Vaz, Ricciuti, Lin, Christiani: None.

Hatabu: reserch funding from Canon Inc., Canon Medical Systems, and Konica-Minolta; consultant to Canon Medical Systems, and Mitsubishi Chemical Inc.

Awad: consultant/advisory board: Genentech, Bristol-Myers Squibb, Merck, AstraZeneca, Maverick, Blueprint Medicine, Syndax, Ariad, Nektar, ArcherDX, Mirati, NextCure, Novartis, EMD Serono. Institutional research funding: from Bristol-Myers Squibb, AstraZeneca, Lilly, Genentech.

Statistics and biometry

Two of the authors have significant statistical expertise (Wang and Lin).

Informed consent

Written informed consent was obtained from all patients in this study.

Ethical approval

Institutional Review Board approval was obtained.

Methodology

• retrospective

• observational

• performed at one institution

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Nishino, M., Wang, X., Ricciuti, B. et al. Advanced non-small-cell lung cancer treated with first-line pembrolizumab plus chemotherapy: tumor response dynamics as a marker for survival. Eur Radiol 33, 7284–7293 (2023). https://doi.org/10.1007/s00330-023-09658-1

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  • DOI: https://doi.org/10.1007/s00330-023-09658-1

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