ESMO 2018: The Role of PD-L1 Status as A Predictor or Prognostic Marker of Clinical Outcomes in Patients Treated on CABOSUN and METEOR

Munich, Germany ( METEOR was a phase 3, open-label, randomized controlled trial which compared the efficacy of cabozantinib to everolimus, for patients with mRCC who had progressed after VEGFR-targeted therapy1. In this study, 658 patients were randomized to either receive cabozantinib at a dose of 60 mg daily or everolimus at a dose of 10 mg daily and the primary endpoint was progression free survival (PFS). This study found that median PFS was 7.4 months with cabozantinib and 3.8 months with everolimus, which established cabozantinib as a reasonable second-line therapy for patients with mRCC.

was a randomized phase II study which brought cabozantinib to the front line and compared it head to head against sunitinib. 157 patients were randomly assigned to therapy, and compared with sunitinib, cabozantinib increased median PFS (8.2 months vs 5.6 months, HR, 0.66, P = .012). The overall response rate to cabozantinib was 33% vs 12% for sunitinib. Based on this study, cabozantinib gained a role for front-line therapy of patients with intermediate or poor-risk mRCC.

This study examined tissue from both of these studies in order to determine whether or not PD-L1 expression could be a prognostic OR predictive biomarker for cabozantinib.

The investigators utilized a novel digital image analysis algorithm to assign a PD-L1 score for both tumor cells and immune cells. PFS and OS associations with PD-L1 were analyzed Cox regression. 

ESMO 2018 staining for PD L1

In terms of prognosis, PD-L1 expression was associated with both shorter PFS and OS in METEOR and CABOSUN. When the patients from METEOR and CABOSUN were combined, PD-L1 positivity had a hazard ratio for death of 1.39 (95%CI1.03-1.87, p=0.034) for all patients and 1.63 (95%CI 1.03-2.60, p=0.038) for patients treated with cabozantinib.

ESMO 2018 PD L1 expression

Cabozantinib was associated with improved PFS and OS compared with everolimus or sunitinib, regardless of PD-L1 expression.

This study uses a novel imaging method to assess for PD-L1 status, utilizing a dual IHC staining method and then digital analysis. PD-L1 was not predictive for individualized therapy as it improved overall survival and progression-free survival over everolimus and sunitinib, irrespective of PD-L1 status. Much controversy exists over PD-L1 assays, and this novel method of scoring PD-L1 may prove useful in standardizing PD-L1 for future studies.  This technology has utilized in cutaneous melanoma and several different groups are evaluating this technology as PD-L1 scoring guides therapy for certain tumor types2-4.

Presented by: Toni K. Choueiri, MD, Dana-Farber Cancer Institute, Department of Medical Oncology, Boston, Massachusetts 

Written by: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University @TheRealJasonZhu at the 2018 European Society for Medical Oncology Congress (#ESMO18), October 19-23,  2018, Munich Germany
1. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus everolimus in advanced renal cell carcinoma. The New England journal of medicine 2015;373:1814-23.
2. Koelzer VH, Gisler A, Hanhart JC, et al. Digital image analysis improves precision of PD‐L1 scoring in cutaneous melanoma. Histopathology 2018.
3. Kearney S, Black J, Aeffner F, Black J, Pratte L, Krueger J. Abstract 4582: Evaluating benefits of PD-L1 image analysis for the clinical setting. Cancer Research 2017;77:4582-.
4. Martin NT, Black JC, Pollack Z, Aeffner F, Krueger J. Abstract 661: Evaluating harmonization of PD-L1 assays using image analysis. Cancer Research 2017;77:661.

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Watch: CABOSUN Trial Plus an In-depth Discussion of Kidney Cancer Treatments - Toni Choueiri