Advanced Non-small-cell Lung Cancer Treated with First-line Pembrolizumab Plus Chemotherapy: Tumor Response Dynamics As a Marker for Survival

Overview

Journal Eur Radiol

Specialty Radiology

Date 2023 Apr 26

PMID 37099174

Authors

Mizuki Nishino

Xinan Wang

Biagio Ricciuti

Shu-Chi Tseng

Hyesun Park

Joao V Alessi

Victor R Vaz

Hiroto Hatabu

Xihong Lin

David C Christiani

Mark M Awad

Affiliations

Soon will be listed here.

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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References

Hodi F, ODay S, Mcdermott D, Weber R, Sosman J, Haanen J . Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010; 363(8):711-23. PMC: 3549297. DOI: 10.1056/NEJMoa1003466. View

Topalian S, Hodi F, Brahmer J, Gettinger S, Smith D, Mcdermott D . Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012; 366(26):2443-54. PMC: 3544539. DOI: 10.1056/NEJMoa1200690. View

Topalian S, Sznol M, Mcdermott D, Kluger H, Carvajal R, Sharfman W . Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014; 32(10):1020-30. PMC: 4811023. DOI: 10.1200/JCO.2013.53.0105. View

Nishino M, Tirumani S, Ramaiya N, Hodi F . Cancer immunotherapy and immune-related response assessment: The role of radiologists in the new arena of cancer treatment. Eur J Radiol. 2015; 84(7):1259-68. PMC: 4450141. DOI: 10.1016/j.ejrad.2015.03.017. View

Reck M, Rodriguez-Abreu D, Robinson A, Hui R, Csoszi T, Fulop A . Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016; 375(19):1823-1833. DOI: 10.1056/NEJMoa1606774. View

Langer C, Gadgeel S, Borghaei H, Papadimitrakopoulou V, Patnaik A, Powell S . Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 2016; 17(11):1497-1508. PMC: 6886237. DOI: 10.1016/S1470-2045(16)30498-3. View

Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gumus M, Mazieres J . Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med. 2018; 379(21):2040-2051. DOI: 10.1056/NEJMoa1810865. View

Mok T, Wu Y, Kudaba I, Kowalski D, Cho B, Turna H . Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019; 393(10183):1819-1830. DOI: 10.1016/S0140-6736(18)32409-7. View

Park H, Sholl L, Hatabu H, Awad M, Nishino M . Imaging of Precision Therapy for Lung Cancer: Current State of the Art. Radiology. 2019; 293(1):15-29. PMC: 6776234. DOI: 10.1148/radiol.2019190173. View

10.

Nishino M, Dahlberg S, Adeni A, Lydon C, Hatabu H, Janne P . Tumor Response Dynamics of Advanced Non-small Cell Lung Cancer Patients Treated with PD-1 Inhibitors: Imaging Markers for Treatment Outcome. Clin Cancer Res. 2017; 23(19):5737-5744. PMC: 5626605. DOI: 10.1158/1078-0432.CCR-17-1434. View

11.

Nishino M, Lu J, Hino T, Vokes N, Janne P, Hatabu H . Tumor Growth Rate After Nadir Is Associated With Survival in Patients With -Mutant Non-Small-Cell Lung Cancer Treated With Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor. JCO Precis Oncol. 2022; 5:1603-1610. PMC: 9848598. DOI: 10.1200/PO.21.00172. View

12.

Nishino M, Giobbie-Hurder A, Manos M, Bailey N, Buchbinder E, Ott P . Immune-Related Tumor Response Dynamics in Melanoma Patients Treated with Pembrolizumab: Identifying Markers for Clinical Outcome and Treatment Decisions. Clin Cancer Res. 2017; 23(16):4671-4679. PMC: 5559305. DOI: 10.1158/1078-0432.CCR-17-0114. View

13.

Park H, Kim K, Pyo J, Suh C, Yoon S, Hatabu H . Incidence of Pseudoprogression during Immune Checkpoint Inhibitor Therapy for Solid Tumors: A Systematic Review and Meta-Analysis. Radiology. 2020; 297(1):87-96. PMC: 7526949. DOI: 10.1148/radiol.2020200443. View

14.

Therasse P, Arbuck S, Eisenhauer E, Wanders J, Kaplan R, Rubinstein L . New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000; 92(3):205-16. DOI: 10.1093/jnci/92.3.205. View

15.

Eisenhauer E, Therasse P, Bogaerts J, Schwartz L, Sargent D, Ford R . New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2008; 45(2):228-47. DOI: 10.1016/j.ejca.2008.10.026. View

16.

Nishino M, Jagannathan J, Ramaiya N, Van Den Abbeele A . Revised RECIST guideline version 1.1: What oncologists want to know and what radiologists need to know. AJR Am J Roentgenol. 2010; 195(2):281-9. DOI: 10.2214/AJR.09.4110. View

17.

Nishino M, Cardarella S, Jackman D, Ramaiya N, Rabin M, Hatabu H . RECIST 1.1 in NSCLC patients with EGFR mutations treated with EGFR tyrosine kinase inhibitors: comparison with RECIST 1.0. AJR Am J Roentgenol. 2013; 201(1):W64-71. PMC: 3731976. DOI: 10.2214/AJR.12.9668. View

18.

Nishino M, Giobbie-Hurder A, Gargano M, Suda M, Ramaiya N, Hodi F . Developing a common language for tumor response to immunotherapy: immune-related response criteria using unidimensional measurements. Clin Cancer Res. 2013; 19(14):3936-43. PMC: 3740724. DOI: 10.1158/1078-0432.CCR-13-0895. View

19.

Nishino M, Jackman D, Hatabu H, Yeap B, Cioffredi L, Yap J . New Response Evaluation Criteria in Solid Tumors (RECIST) guidelines for advanced non-small cell lung cancer: comparison with original RECIST and impact on assessment of tumor response to targeted therapy. AJR Am J Roentgenol. 2010; 195(3):W221-8. PMC: 3130298. DOI: 10.2214/AJR.09.3928. View

20.

Nishino M, Giobbie-Hurder A, Ramaiya N, Hodi F . Response assessment in metastatic melanoma treated with ipilimumab and bevacizumab: CT tumor size and density as markers for response and outcome. J Immunother Cancer. 2014; 2(1):40. PMC: 4236430. DOI: 10.1186/s40425-014-0040-2. View