Journal
CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 70, Issue 6, Pages 1583-1592Publisher
SPRINGER
DOI: 10.1007/s00262-020-02788-1
Keywords
NSCLC; Pembrolizumab; Serum amyloid A; Biomarker of response; Predictive; prognostic factors to immune-checkpoint inhibitors
Categories
Funding
- Fondazione Roche (Bando per la Ricerca Roche)
- Institutional funds of Universita Cattolica del Sacro Cuore (UCSC) [D1-2019]
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [IG20583]
- AIRC [IG18599]
- AIRC 5x1000 [21052]
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The study shows that blood serum amyloid A (SAA) can serve as a biomarker for predicting treatment response to upfront pembrolizumab in patients with advanced non-small-cell lung cancer (NSCLC). Low SAA levels predict good survival outcomes regardless of treatment, but with a higher likelihood of response to upfront pembrolizumab.
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.
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