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Blood serum amyloid A as potential biomarker of pembrolizumab efficacy for patients affected by advanced non-small cell lung cancer overexpressing PD-L1: results of the exploratory 'FoRECATT' study
- Source :
- Cancer Immunology, Immunotherapy
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media Deutschland GmbH, 2020.
-
Abstract
- BackgroundIdentifying the patients who may benefit the most from immune checkpoints inhibitors remains a great challenge for clinicians. Here we investigate on blood serum amyloid A (SAA) as biomarker of response to upfront pembrolizumab in patients with advanced non-small-cell lung cancer (NSCLC).MethodsPatients with PD-L1 ≥ 50% receiving upfront pembrolizumab (P cohort) and with PD-L1 0–49% treated with chemotherapy (CT cohort) were evaluated for blood SAA and radiological response at baseline and every 9 weeks. Endpoints were response rate (RR) according to RECIST1.1, progression-free (PFS) and overall survival (OS). The most accurate SAA cut-off to predict response was established with ROC analysis in the P cohort.ResultsIn the P Cohort (n = 42), the overall RR was 38%. After a median follow-up of 18.5 months (mo), baseline SAA ≤ the ROC-derived cut-off (29.9 mg/L;n = 28/42.67%) was significantly associated with higher RR (53.6 versus 7.1%; OR15, 95% CI 1.72–130.7,p = 0.009), longer PFS (17.4 versus 2.1 mo;p p 29.9 mg/L. In multivariate analysis, low SAA positively affects PFS (p = 0.001) and OS (p = 0.048) irrespective of ECOG PS, number of metastatic sites and pleural effusion. SAA monitoring (n = 40) was also significantly associated with survival endpoints: median PFS 17.4 versus 2.1 mo and median OS not reached versus 7.2 mo when SAA remained low (n = 14) and high (n = 12), respectively. In the CT Cohort (n = 30), RR was not affected by SAA level (p > 0.05) while low SAA at baseline (n = 17) was associated with better PFS (HR 0.38, 95% CI 0.16–0.90,p = 0.006) and OS (HR 0.25, 95% CI 0.09–0.67,p ConclusionLow SAA predicts good survival outcomes irrespective of treatment for advanced NSCLC patients and higher likelihood of response to upfront pembrolizumab only. The strong prognostic value might be exploited to easily identify patients most likely to benefit from immunotherapy. A further study (FoRECATT-2) is ongoing to confirm results in a larger sample size and to investigate the effect of SAA on immune response in vitro assays.
- Subjects :
- Oncology
Male
Cancer Research
Lung Neoplasms
Pleural effusion
medicine.medical_treatment
Pembrolizumab
NSCLC
B7-H1 Antigen
0302 clinical medicine
Blood serum
Antineoplastic Agents, Immunological
Carcinoma, Non-Small-Cell Lung
Monoclonal
80 and over
Immunology and Allergy
030212 general & internal medicine
Prospective Studies
Non-Small-Cell Lung
Humanized
Aged, 80 and over
Tumor
Middle Aged
Prognosis
Survival Rate
Immunological
030220 oncology & carcinogenesis
Cohort
Carcinoma, Squamous Cell
Biomarker (medicine)
Female
Original Article
Biomarker of response
Adult
medicine.medical_specialty
Immunology
Antineoplastic Agents
Adenocarcinoma of Lung
Antibodies, Monoclonal, Humanized
Antibodies
03 medical and health sciences
Predictive/prognostic factors to immune-checkpoint inhibitors
Internal medicine
medicine
Biomarkers, Tumor
Humans
Serum amyloid A
Lung cancer
Aged
Chemotherapy
Serum Amyloid A Protein
Settore MED/06 - ONCOLOGIA MEDICA
business.industry
Carcinoma
medicine.disease
Squamous Cell
Case-Control Studies
business
Biomarkers
Follow-Up Studies
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Cancer Immunology, Immunotherapy
- Accession number :
- edsair.doi.dedup.....6fff3a0c94ab17be43b3cbb90244d676