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Poster display session

1683 - Association of single nucleotide polymorphisms with efficacy in nivolumab-treated NSCLC patients


09 Sep 2017


Poster display session


Cancers in Adolescents and Young Adults (AYA);  Immunotherapy;  Translational Research;  Non-Small Cell Lung Cancer


Edwin Basak


Annals of Oncology (2017) 28 (suppl_5): v460-v496. 10.1093/annonc/mdx380


E.A. Basak1, S. Bins1, S. El Bouazzaoui2, S.L.W. Koolen1, E. Oomen-De Hoop1, C. van der Leest3, A.A.M. van der Veldt1, S. Sleijfer1, R. Debets1, R.H.N. van Schaik2, R.H.J. Mathijssen1, J.G.J.V. Aerts4

Author affiliations

  • 1 Medical Oncology, Erasmus MC Cancer Institute, 3075 EA - Rotterdam/NL
  • 2 Clinical Chemistry, Erasmus University Medical Center, 3015 CE - Rotterdam/NL
  • 3 Pulmonology, Amphia Hospital, 4818 CK - Breda/NL
  • 4 Pulmonology, Erasmus University Medical Center, 3015 CE - Rotterdam/NL


Abstract 1683


Proper patient selection for PD-1 checkpoint inhibitors is crucial given its limited efficacy in the majority of patients. We previously showed that a single nucleotide polymorphism (SNP) in the auto-immunity (AI) related PTPN11 gene (rs2301756) is associated with increased toxicity on nivolumab (Bins et al, ESMO immuno-oncology symp, 2016). The objective of the current analysis was to assess whether SNPs in PTPN11 and other genes associated with AI, which are putatively considered important in PD-1 influenced T-cell responses, are correlated with treatment efficacy of nivolumab in NSCLC patients.


The association between 5 SNPs and efficacy was evaluated in 161 (chemotherapy pretreated) advanced NSCLC patients. Efficacy measures included early progressive disease (PD; ≤ 90 days after start), tumor response according to RECISTv1.1, PFS and OS. The SNPs were located on 4 genes, being PDCD1, PTPN11, ZAP70 and IFNG, respectively, encoding for the proteins PD-1, SHP-2 and ZAP70 and IFN-γ. The best model for every SNP, being either a dominant, recessive, multiplicative or additive model, was selected. SNPs were analyzed in multivariable logistic regression models if they showed a p-value


Overall, 54 patients showed PR or CR according to RECIST. Patients with at least one variant allele in PTPN11 had a higher response rate compared to wild-type (50% vs 30%; OR 2.4; 95% CI 1.0 – 5.5; p = 0.042). Other SNPs were not associated with response rate, and none of these SNPs were associated with early PD. Until the day of analysis, at which 128 patients had PD and 107 patients were dead, none of the SNPs was associated with PFS or OS.


Our results show that the SNP in PTPN11 predisposes for a higher response rate to nivolumab therapy. Together with our earlier finding that this SNP is associated with grade ≥ 3 toxicity, this may indicate that SHP-2 activity influences treatment outcome of anti-PD-1 therapy in terms of both toxicity and anti-tumor effects. If confirmed, SNPs in PTPN11 should be considered to be included as a biomarker in routine analysis of NSCLC patients to be treated with nivolumab.

Clinical trial identification

Legal entity responsible for the study

Erasmus University Medical Center




S. Bins: Speaker for Astellas, travel grants from Pfizer and Roche. C. van der Leest: Honorarium from Roche, BMS, MSD and Boehringer Ingelheim, advisory board for BMS and Boehringer Ingelheim. A.A.M. van der Veldt: Advisory board for BMS, Ipsen and Pfizer. R. Debets: Co-PI in “Pembrolizumab study in metastasized urothelial cancers” sponsored by Merck and consulant/reviewer various immunotherapy studies. J.G.J.V. Aerts: Grants and personal fees from BMS, personal fees from MSD, Boehringer Ingelheim, Astra Zeneca, Eli-Lilly and Roche, non-financial support from Eli-Lilly and Pfizer. Patent pending. All other authors have declared no conflicts of interest.

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