TY - JOUR
T1 - Blood serum amyloid A as potential biomarker of pembrolizumab efficacy for patients affected by advanced non-small cell lung cancer overexpressing PD-L1
T2 - results of the exploratory “FoRECATT” study
AU - Di Noia, Vincenzo
AU - D’Argento, Ettore
AU - Pilotto, Sara
AU - Vita, Emanuele
AU - Ferrara, Miriam Grazia
AU - Damiano, Paola
AU - Ribelli, Marta
AU - Cannella, Antonella
AU - Virtuoso, Antonella
AU - Fattorossi, Andrea
AU - Ceresoli, Giovanni Luca
AU - Milella, Michele
AU - Beretta, Giordano Domenico
AU - Tortora, Giampaolo
AU - Bria, Emilio
N1 - Funding Information:
The FoRECATT study is supported by Fondazione Roche (“Bando per la Ricerca Roche 2019”) and Institutional funds of Università Cattolica del Sacro Cuore (UCSC-project D1-2019). E.B. is currently supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) under Investigator Grant (IG) No. IG20583. G.T. is supported by AIRC, IG18599, AIRC 5x1000 21052.
Funding Information:
V.D.N. received speakers’ fee by Astrazeneca, MSD, BMS, Istituto Gentili, Boehringer Ingelheim. V.D.N. received grant consultancies by Astrazeneca, MSD, BMS, Boehringer Ingelheim and travels’ fee from MSD and Boehringer Ingelheim. V.D.N. received institutional research grants from Roche. E.B. received speakers’ and travels’ fee from MSD, Astra-Zeneca, Celgene, Pfizer, Helsinn, Eli-Lilly, BMS, Novartis and Roche. E.B received consultant’s fee from Roche, Pfizer. E.B. received institutional research grants from Astra-Zeneca, Roche.
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - Background: Identifying 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). Methods: Patients 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. Results: In 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 < 0.0001) and OS (not reached versus 7.2mo; p < 0.0001) compared with SAA > 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 < 0.001). Conclusion: Low 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.
AB - Background: Identifying 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). Methods: Patients 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. Results: In 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 < 0.0001) and OS (not reached versus 7.2mo; p < 0.0001) compared with SAA > 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 < 0.001). Conclusion: Low 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.
KW - Biomarker of response
KW - NSCLC
KW - Pembrolizumab
KW - Predictive/prognostic factors to immune-checkpoint inhibitors
KW - Serum amyloid A
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U2 - 10.1007/s00262-020-02788-1
DO - 10.1007/s00262-020-02788-1
M3 - Article
AN - SCOPUS:85096551448
JO - Cancer Immunology and Immunotherapy
JF - Cancer Immunology and Immunotherapy
SN - 0340-7004
ER -