The Phase 3 IMmotion151 trial demonstrated that the combination of atezolizumab (atezo) and bevacizumab (bev) demonstrated an improved PFS compared to sunitinib (sun) alone in untreated mRCC pts, 362 (40%) of 915 patients had PD-L1 positive disease. In that study, they found that in the PD-L1 positive population, the median progression-free survival was 11·2 months in the atezolizumab plus bevacizumab group versus 7·7 months in the sunitinib group (hazard ratio [HR] 0·74 [95% CI 0·57-0·96]; p=0·0217). In the ITT population, median overall survival had an HR of 0·93 (0·76-1·14) and the results did not cross the significance boundary at the interim analysis.
In this presentation at ASCO 2019, the authors report the results of a prespecified subgroup analysis in patients whose tumors have sarcomatoid histology, which is an independent predictor of poor survival. 10-20% of patients with advanced disease are thought to harbor sarcomatoid histology and have a limited response to targeted therapies. The IMmotion-151 study only included patients with clear cell histology and sarcomatoid histology.
The full study protocol is seen below:
![ASCO2019_studyprotocol_4512.png](/images/ASCO2019_studyprotocol_4512.png)
Of the 915 patients, 142 randomized pts (16%) from IMmotion151 had tumors with any component of sarcomatoid histology. Full demographics of the 142 patients and the entire cohort are seen below:
![ASCO2019_fulldemographics_4512.png](/images/ASCO2019_fulldemographics_4512.png)
In this group with sarcomatoid histology, median PFS was 8.3 vs 5.3 mo with atezo + bev vs sun and median OS was 21.7 vs 15.4 mo, respectively. The table below summarizes results in all sarcomatoid patients and in patients who were PD-L1+ as well.
![ASCO2019_efficiancysummary_4512.png](/images/ASCO2019_efficiancysummary_4512.png)
Looking at the KM curves for PFS and OS (below), patients with sarcomatoid histology treated with atezo/bev had significantly longer PFS and OS. This was true regardless of PD-L1 status.
![ASCO2019_figure_2_3_4512.png](/images/ASCO2019_figure_2_3_4512.png)
![ASCO2019_figure4_4512.png](/images/ASCO2019_figure4_4512.png)
Looking at the genomic evaluation, prevalence of Angiogenesis-High gene expression (GE) signature subset was lower (34% vs 65%) and T-effector-High GE subset was higher (54% vs 40%) in sarc vs non-sarc tumors. PD-L1+ disease was more common in sarc vs non-sarc tumors (63% vs 39%). These are summarized below:
![ASCO2019_figure_5_4512.png](/images/ASCO2019_figure_5_4512.png)
Clinical Trial information: NCT02420821
Presented by: Brian I. Rini, Medical Oncologist, Cleveland Clinic, Cleveland, OH
Co-authors: Robert J. Motzer, Thomas Powles, David F. McDermott, Bernard Escudier, Frede Donskov, Robert E. Hawkins, Sergio Bracarda, Jens Bedke, Ugo De Giorgi, Camillo Porta, Alain Ravaud, Francis Parnis, Enrique Grande, Wei Zhang, Mahrukh A. Huseni, Susheela Carroll, Roxana Ioana Sufan, Christina Schiff, Michael B. Atkins
Written by: Thenappan Chandrasekar, MD, Clinical Instructor, Thomas Jefferson University, @tchandra_uromd, @JEFFUrology, at the 2019 ASCO Annual Meeting #ASCO19, May 31-June 4, 2019, Chicago, IL USA
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