Immunotherapy and VEGF-targeting therapies improve mRCC outcomes; however, immune escape and/or resistance often develops so new agents and combinations are needed. The authors previously reported initial results of IMmotion150 , noting a progression free survival (PFS) HR of 0.64 (95%CI 0.38-1.08) for patients receiving atezolizumab + bevacizumab vs sunitinib. The purpose of the current study was to update results from the IMmotion150 trial, as well as explore novel radiologic endpoints for these agents in the first-line setting for mRCC.
Treatment-naive mRCC patients were randomized (1:1:1) to atezolizumab 1200 mg IV q3w + bevacizumab 15 mg/kg IV q3w (n=101 ITT; n=50 PD-L1 +) vs atezolizumab 1200 mg IV q3w alone (n=103; n=54 PD-L1 +) vs sunitinib 50 mg PO QD 4 wk on/2 wk off (n=101; n=60 PD-L1 +). PD-L1 expression was scored on tumor-infiltrating immune cells. The co-primary endpoints were independent review–assessed PFS (RECIST v1.1) in the intention to treat cohort and PD-L1 + (≥ 1%) patients. Other additional endpoints included investigator-assessed PFS by RECIST v1.1 and immune-modified RECIST (imRECIST).
After a median 25.7 months of follow-up, the results remained consistent with the primary analysis (median follow-up, 20.7 months), showing clinically meaningful benefit in independent- and investigator reviewed-PFS with atezolizumab + bevacizumab vs sunitinib in PD-L1+ patients (RECIST v1.1): independent PFS HR 0.65 (95%CI 0.40-1.05); investigator PFS HR 0.60 (95%CI 0.38-0.94). The investigator-PFS (imRECIST) HR for atezolizumab + bevacizumab vs sunitinib was 0.78 (95%CI 0.55-1.11) in intention to treat patients and 0.47 in PD-L1+ patients (95%CI 0.29-0.78). Safety of atezolizumab + bevacizumab was consistent with the known safety profile of each agent alone and further follow-up showed no new safety signals.
In summary, updated efficacy (RECIST v1.1) confirmed the encouraging activity of atezolizumab + bevacizumab in PD-L1+ first-line mRCC, with no new safety signals. Data per imRECIST, compared with RECIST v1.1, showed benefit of atezolizumab + bevacizumab in PD-L1+ and intention to treat patients and may contribute to our understanding of the clinical activity of cancer immunotherapy in mRCC. Furthermore, the clinical benefit of atezolizumab + bevacizumab vs sunitinib will be further evaluated in the ongoing phase III study IMmotion151 (NCT02420821).
Speaker: Thomas Powles, Barts Cancer Institute ECMC, Barts Health and the Royal Free NHS Trust, Queen Mary University of London, London, United Kingdom
Co-Authors: D. F. McDermott (Boston, United States of America) B. Rini (Cleveland, United States of America) R. J. Motzer (New York, United States of America) M. B. Atkins (Washington DC, United States of America) L. Fong (San Francisco, United States of America) R. W. Joseph (Jacksonville, United States of America) S. K. Pal (Duarte, United States of America) A. Ravaud (Bordeaux, France) S. Bracarda (Arezzo, Italy) C. Suarez Rodriguez (Barcelona, Spain) M. Maio (Siena, Italy) M. Gore (London, United Kingdom) V. Grünwald (Hannover, Germany) M. Staehler (Munich, Germany) J. Qiu (South San Francisco, United States of America) A. Thobhani (Welwyn Garden City, United Kingdom) M. Huseni (South San Francisco, United States of America) C. Schiff (South San Francisco, United States of America) B. Escudier (Villejuif, France)
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain