Early On-treatment C-reactive Protein and Its Kinetics Predict Survival and Response in Recurrent And/or Metastatic Head and Neck Cancer Patients Receiving First-line Pembrolizumab

Overview

Journal Invest New Drugs

Publisher Springer

Specialty Oncology

Date 2023 Aug 21

PMID 37603206

Authors

Markus Haas

Alexander Lein

Thorsten Fuereder

Julia Schnoell

Faris F Brkic

David T Liu

Lorenz Kadletz-Wanke

Gregor Heiduschka

Bernhard J Jank

Affiliations

Soon will be listed here.

Abstract

Purpose: First-line immune checkpoint blockade has improved the prognosis of recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC), but response rates remain low. In this study, we aimed to investigate the prognostic value of CRP and its early kinetics to predict response and survival in R/M HNSCC.

Methods: A total of 87 patients who received first-line pembrolizumab for R/M HNSCC were analyzed. Three-fold cross-validation was used to estimate cut-off points of CRP at baseline and on-treatment (day 40 ± 10). Treatment response and survival were analyzed according to early CRP kinetics. The neutrophil-to-lymphocyte ratio (NLR) was used as a benchmark for the prognostic performance of CRP.

Results: On-treatment CRP below 2 mg/dl, 4x the upper limit of normal (ULN), was associated with increased overall survival (OS), while on-treatment CRP below 3 mg/dl (6x ULN) was correlated with a higher disease control rate (DCR) and increased progression-free survival (PFS). CRP flare-responders and CRP responders showed a higher DCR and longer PFS than CRP non-responders. An NLR above 6 was a negative prognosticator for progression. In multivariable analysis, on-treatment CRP prevailed as the only significant prognosticator for OS (HR: 4.97, CI95%: 2.18-11.32, p < 0.001) and PFS (HR: 2.07, CI95%: 1.07-3.99, p = 0.030).

Conclusion: On-treatment CRP was identified as a prognostic biomarker for objective response and survival in R/M HNSCC patients receiving first-line pembrolizumab and could be easily incorporated into clinical practice as a widely available and cost-effective biomarker.

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References

Matsuo M, Yasumatsu R, Masuda M, Toh S, Wakasaki T, Hashimoto K . Inflammation-based Prognostic Score as a Prognostic Biomarker in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma Treated With Nivolumab Therapy. In Vivo. 2022; 36(2):907-917. PMC: 8931916. DOI: 10.21873/invivo.12780. View

Saleh K, Daste A, Martin N, Pons-Tostivint E, Auperin A, Herrera-Gomez R . Response to salvage chemotherapy after progression on immune checkpoint inhibitors in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. Eur J Cancer. 2019; 121:123-129. DOI: 10.1016/j.ejca.2019.08.026. View

Youden W . Index for rating diagnostic tests. Cancer. 1950; 3(1):32-5. DOI: 10.1002/1097-0142(1950)3:1<32::aid-cncr2820030106>3.0.co;2-3. View

Yoshida T, Ichikawa J, Giuroiu I, Laino A, Hao Y, Krogsgaard M . C reactive protein impairs adaptive immunity in immune cells of patients with melanoma. J Immunother Cancer. 2020; 8(1). PMC: 7204799. DOI: 10.1136/jitc-2019-000234. View

Koukourakis M, Kambouromiti G, Pitsiava D, Tsousou P, Tsiarkatsi M, Kartalis G . Serum C-reactive protein (CRP) levels in cancer patients are linked with tumor burden and are reduced by anti-hypertensive medication. Inflammation. 2009; 32(3):169-75. DOI: 10.1007/s10753-009-9116-4. View

. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017; 390(10100):1211-1259. PMC: 5605509. DOI: 10.1016/S0140-6736(17)32154-2. View

Matsuki T, Okamoto I, Fushimi C, Sawabe M, Kawakita D, Sato H . Hematological predictive markers for recurrent or metastatic squamous cell carcinomas of the head and neck treated with nivolumab: A multicenter study of 88 patients. Cancer Med. 2020; 9(14):5015-5024. PMC: 7367642. DOI: 10.1002/cam4.3124. View

Fukuda S, Saito K, Yasuda Y, Kijima T, Yoshida S, Yokoyama M . Impact of C-reactive protein flare-response on oncological outcomes in patients with metastatic renal cell carcinoma treated with nivolumab. J Immunother Cancer. 2021; 9(2). PMC: 7896625. DOI: 10.1136/jitc-2020-001564. View

Burtness B, Harrington K, Greil R, Soulieres D, Tahara M, de Castro Jr G . Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019; 394(10212):1915-1928. DOI: 10.1016/S0140-6736(19)32591-7. View

10.

Klumper N, Saal J, Berner F, Lichtensteiger C, Wyss N, Heine A . C reactive protein flare predicts response to checkpoint inhibitor treatment in non-small cell lung cancer. J Immunother Cancer. 2022; 10(3). PMC: 8928397. DOI: 10.1136/jitc-2021-004024. View

11.

Rasmussen J, Lelkaitis G, Hakansson K, Vogelius I, Johannesen H, Fischer B . Intratumor heterogeneity of PD-L1 expression in head and neck squamous cell carcinoma. Br J Cancer. 2019; 120(10):1003-1006. PMC: 6734649. DOI: 10.1038/s41416-019-0449-y. View

12.

Minichsdorfer C, Gleiss A, Aretin M, Schmidinger M, Fuereder T . Serum parameters as prognostic biomarkers in a real world cancer patient population treated with anti PD-1/PD-L1 therapy. Ann Med. 2022; 54(1):1339-1349. PMC: 9103267. DOI: 10.1080/07853890.2022.2070660. View

13.

Ueki Y, Takahashi T, Ota H, Shodo R, Yamazaki K, Horii A . Predicting the treatment outcome of nivolumab in recurrent or metastatic head and neck squamous cell carcinoma: prognostic value of combined performance status and modified Glasgow prognostic score. Eur Arch Otorhinolaryngol. 2020; 277(8):2341-2347. DOI: 10.1007/s00405-020-05945-5. View

14.

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

15.

Nenclares P, Gunn L, Soliman H, Bover M, Trinh A, Leslie I . On-treatment immune prognostic score for patients with relapsed and/or metastatic head and neck squamous cell carcinoma treated with immunotherapy. J Immunother Cancer. 2021; 9(6). PMC: 8190047. DOI: 10.1136/jitc-2021-002718. View

16.

Yasumatsu R, Wakasaki T, Hashimoto K, Nakashima K, Manako T, Taura M . Monitoring the neutrophil-to-lymphocyte ratio may be useful for predicting the anticancer effect of nivolumab in recurrent or metastatic head and neck cancer. Head Neck. 2019; 41(8):2610-2618. DOI: 10.1002/hed.25737. View

17.

Aspeslagh S, Matias M, Palomar V, Dercle L, Lanoy E, Soria J . In the immuno-oncology era, is anti-PD-1 or anti-PD-L1 immunotherapy modifying the sensitivity to conventional cancer therapies?. Eur J Cancer. 2017; 87:65-74. DOI: 10.1016/j.ejca.2017.09.027. View

18.

Mehra R, Seiwert T, Gupta S, Weiss J, Gluck I, Eder J . Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012. Br J Cancer. 2018; 119(2):153-159. PMC: 6048158. DOI: 10.1038/s41416-018-0131-9. View

19.

Argiris A, Harrington K, Tahara M, Schulten J, Chomette P, Castro A . Evidence-Based Treatment Options in Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck. Front Oncol. 2017; 7:72. PMC: 5422557. DOI: 10.3389/fonc.2017.00072. View

20.

Seymour L, Bogaerts J, Perrone A, Ford R, Schwartz L, Mandrekar S . iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol. 2017; 18(3):e143-e152. PMC: 5648544. DOI: 10.1016/S1470-2045(17)30074-8. View