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Poster display session

3679 - Immune expression profile and sunitinib benefit in metastatic clear cell renal cell carcinoma (ccRCC)

Date

10 Sep 2017

Session

Poster display session

Topics

Cytotoxic Therapy;  Renal Cell Cancer

Presenters

Oscar Reig Torras

Citation

Annals of Oncology (2017) 28 (suppl_5): v295-v329. 10.1093/annonc/mdx371

Authors

O. Reig Torras1, M. Marín_aguilera1, N. Jimenez1, L. Paré1, P. Galvan1, C. Mallofre2, A. Prat1, B. Mellado Gonzalez1

Author affiliations

  • 1 Medical Oncology, Hospital Clinic y Provincial de Barcelona, 8036 - Barcelona/ES
  • 2 Pathology, Hospital Clinic y Provincial de Barcelona, 8036 - Barcelona/ES
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Resources

Abstract 3679

Background

The identification of predictive biomarkers may be useful to select antiangiogenic or immunotherapy treatment in renal cell carcinoma. We here investigated the immune expression profile in sunitinib (SU) or anti-PD1/PD-L1 treated ccRCC patients.

Methods

Forty-two metastatic ccRCC patients treated with SU and 10 patients treated with anti-PD1/PD-L1 antibodies were included in this retrospective biomarker study. 730 immune-related genes (nCounter® PanCancer Immune Profiling Panel, Nanostring) were tested in FFPE tumor specimens. Different immune gene signatures were correlated with clinical outcome. A differential expression analysis between refractory (progression-free survival (PFS) < 3 months) and sensitive (PFS > 3 months) patients to SU and anti-PD1/PD-L1 therapies was performed.

Results

Patients who achieved a partial or complete (P/CR) response with SU had a higher score of B cell, CD8 T cell, T cell, Th1 cell, Th2 cell, Treg cell and Stromal signatures. Moreover, these signatures were predictive of P/CR to sunitinib (p-value for odds ratio < 0.05). T cell signatures (CD8 T cell, T cell, Th1 cell, Th2 cell and Treg cell) were correlated with a better PFS, while activated dendritic cell (aDC) and stromal signatures were correlated with a better OS (Table). In the cohort of anti-PD-1/PD-L1 treated patients, no differences in the immune signatures were found between responders and no-responders to these drugs. However, differential expression analysis revealed a single gene, TIM-3, that was associated with resistance to anti-PD1/PD-L1 therapies and benefit to SU in ccRCC patients.Table:

898P

SignaturesProgression-Free SurvivalOverall Survival
HR (95% CI)PHR (95% CI)P
CD8Tcell0.57 (0.37 – 0.89)0.012350.64 (0.39 – 1.03)0.0684
Th1cell0.62 (0.41 – 0.95)0.028410.70 (0.43 – 1.14)0.1491
Tcell0.68 (0.48 – 0.98)0.039510.79 (0.52 – 1.19)0.2649
Tregcell0.67 (0.45 – 0.98)0.041260.76 (0.49 – 1.18)0.2146
Th2cell0.48 (0.24 – 0.97)0.041550.62 (0.30 – 1.26)0.1853
Stromal0.72 (0.50 – 1.03)0.069230.64 (0.43 – 0.96)0.0291
Bcell0.69 (0.47 – 1.03)0.072710.74 (0.48 – 1.14)0.1698
aDC0.78 (0.46 – 1.34)0.371360.53 (0.29 – 0.95)0.0330
iDC0.91 (0.52 – 1.58)0.740050.69 (0.37 – 1.32)0.2649

Conclusions

T cell signatures may be associated with benefit to SU in ccRCC. The value of TIM-3 as a potential biomarker in ccRCC merits further exploration.

Clinical trial identification

Legal entity responsible for the study

Hospital Clínic de Barcelona

Funding

Fundació Clínic per a la Recerca Biomèdica

Disclosure

All authors have declared no conflicts of interest.

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