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Poster Discussion session - Genitourinary tumours, non prostate

4057 - PD-L1 status and clinical outcomes to cabozantinib, sunitinib and everolimus in patients with metastatic clear-cell RCC treated on CABOSUN and METEOR clinical trials.

Date

20 Oct 2018

Session

Poster Discussion session - Genitourinary tumours, non prostate

Topics

Cytotoxic Therapy;  Clinical Research

Tumour Site

Renal Cell Cancer

Presenters

Toni Choueiri

Authors

T.K. Choueiri1, A. Flaifel2, W. Xie3, D. Braun1, M. Ficial2, R. Jennings2, A. Nassar1, B. Escudier4, D.J. George5, R.J. Motzer6, M.J. Morris6, T. Powles7, E. Wang8, Y. Huang9, G. Freeman1, S. Signoretti2

Author affiliations

  • 1 Medical Oncology, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 2 Pathology, Brigham and Women's Hospital, 02215 - Boston/US
  • 3 Biostatistics And Computational Biology, Dana Farber Cancer Institute, Boston/US
  • 4 Medical Oncology, Gustave Roussy Institut de Cancérologie, 94805 - Villejuif/FR
  • 5 Medical Oncology, Duke University Medical Center, 27710 - Durham/US
  • 6 Medicine, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 7 Experimental Cancer Medicine, Barts Cancer Institute, EC1M 6BQ - London/GB
  • 8 Translational Medicine, Exelixis, Inc., 94080 - South San Francisco/US
  • 9 Oncologic Pathology, Dana-Farber Cancer Institute, 02215 - Boston/US
More

Resources

Abstract 4057

Background

PD-L1 status by immunohistochemistry (IHC) is a potential biomarker in metastatic renal cell carcinoma. PD-L1 expression on tumor cells (TC) was associated with improved outcomes in patients (pts) treated with nivolumab+ipilimumab. Cabozantanib (Cabo) is an option for 1st and 2nd line therapy based on CABOSUN (Alliance A031203) and METEOR randomized trials respectively. Here we explore if PD-L1 expression is a prognostic and/or predictive biomarker for Cabo.

Methods

IHC double-staining for PD-L1 and CD45/CD163 (immune cell markers) was performed on formalin-fixed paraffin-embedded baseline tumor tissue from CABOSUN (n=110) and METEOR (n=306) trials. Percentages of PD-L1+ TC or immune cells (IC) were assessed by image analysis. We used Fisher’s exact test to compare RECIST overall response rate (ORR) between PD-L1 positive (>=1% cutoff) vs negative tumors. We used Cox regression to correlate progression-free and overall survival (PFS, OS) with PD-L1 TC expression across each treatment arm. ORR, PFS and OS were per independent central review.

Results

PD-L1+TC was 29% and 23% on METEOR and CABOSUN. In univariable analysis, pts with PD-L1+ TC had poorer PFS and OS on both trials independent of therapy (METEOR: PFS: median 7.2 vs 5.3 mo, p=0.027; OS: 21.3 vs 15.1 mo, p=0.003: CABOSUN: PFS 8.3 vs 5.5 mo, p=0.05; OS 28.1 vs 20.8 mo, p=0.05). Differences were not statistically significant in multivariable analyses adjusted for IMDC prognostic risk groups and bone metastasis. Cabo was associated with improved PFS, OS and ORR compared to everolimus (METEOR) and sunitinib (CABOSUN) irrespective of PD-L1 expression. Results were consistent across PD-L1 measures including IC PD-L1, combined PD-L1 score and using different PD-L1 cutoffs.

Treatment comparison on PFS by PD-L1 expression
METEOR CABOSUN
TC PD-L1 Expression Median, mos (95%CI) HR(95%CI) Median, mos (95%CI) HR(95%CI)
<1%

Cabo (n=112):

8.5 (7.2-13.5)

0.46 (0.32-0.66)

Cabo (n=52):

11.0 (6.8-15.6)

0.47 (0.26-0.86)

Everolimus (n=106):

4.1 (3.7-6)

Sunitinib (n=33):

5.0 (3-12.9)
>=1%

Cabo (n=38):

5.6 (4.5-7.4)
0.66 (0.40-1.11)

Cabo (n=9):

8.4(1.1-16.6)

0.46 (0.18-1.21)

Everolimus (n=50):

3.7 (2-5.3)

Sunitinib (n=16):

3.1(1.6-10.1)

Conclusions

Our data support use of Cabo in a PD-L1 unselected population and possibly in combination with checkpoint blockers irrespective of PD-L1 status.

Support: U10CA180821

Clinical trial identification

NCT01865747

NCT01835158

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