Abstract 3025
Background
Atezo (anti–PD-L1) + bev (anti-VEGF) demonstrated improved PFS and favourable safety vs sun in Ph II and III trials in patients (pts) with untreated mRCC (McDermott 2018; Motzer ASCO GU 2018). To further explore the improved tolerability with this regimen, we performed additional safety analyses using pooled data from the atezo + bev and sun arms of these studies.
Methods
Safety data were assessed from the primary analyses of the Ph II IMmotion150 and Ph III IMmotion151 trials, which enrolled treatment-naive pts with mRCC with clear-cell and/or sarcomatoid histology. Pts were randomised 1:1 to receive atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w or sun 50 mg PO QD 4 wk on/2 wk off until progression (RECIST v1.1) or loss of clinical benefit.
Results
Pooled cohorts included 552 atezo + bev–treated pts and 546 sun-treated pts. Mean duration of treatment for atezo + bev was 11.4 mo for atezo and 10.8 mo for bev vs 10.0 mo for sun. Treatment-related AEs (TRAEs) occurred in 91% of pts with atezo + bev and 96% with sun. Grade 3-4 TRAEs were reported in 40% and 54% of pts with atezo + bev and sun, respectively, with hypertension (14%, 16%), proteinuria (4%, 1%) and fatigue (1%, 6%) as the most common reported events. Grade 5 TRAEs occurred in 1% of pts in each cohort. TRAEs leading to treatment regimen (atezo + bev or sun) discontinuation occurred in 5% of pts with atezo + bev and 8% with sun. AEs of special interest (AESIs), commonly reported with atezo treatment regardless of investigator attribution, were Grade 1-2 in 79% of pts receiving atezo + bev and 78% receiving sun. Corticosteroid use for AESIs (mostly Grade 1-2) occurred in 16% of pts with atezo + bev and 5% with sun. The safety profile in pts with components of sarcomatoid histology or with PD-L1+ tumours was similar to that in pts with clear-cell mRCC. Additional safety data will be reported.
Conclusions
Atezo + bev had a tolerable safety profile in mRCC, with fewer high-grade TRAEs and TRAEs leading to regimen discontinuation than with sun. Corticosteroid use for atezo AESIs was low. Toxicities were consistent with each agent alone, and no new toxicities were identified.
Clinical trial identification
NCT01984242, NCT02420821.
Legal entity responsible for the study
F. Hoffmann-La Roche AG.
Funding
F. Hoffmann-La Roche AG.
Editorial Acknowledgement
Medical writing assistance for this abstract was provided by Paige S. Davies, PhD, of Health Interactions.
Disclosure
T.K. Choueiri: Personal fees: Roche; Personal fees: Pfizer; Grants and personal fees: BMS; Personal fees: Merck; Personal fees: Eisai; Personal fees: Novartis, during the conduct of the study. D.F. McDermott: Consulting or advisory role: Bristol-Myers Squibb, Merck, Genentech/Roche, Pfizer, Novartis, Exelixis, X4 Pharma, Array BioPharma; Research funding: Prometheus Laboratories to institution. B. Escudier: Consulting or advisory role: Bristol-Myers Squibb, Bayer, Pfizer, Novartis, Exelixis, Ipsen, EUSA Pharma; Travel, accommodations, expenses funding: Novartis, Pfizer, Bristol-Myers Squibb; Honoraria: Bristol-Myers Squibb, Bayer, Pfizer, Novartis, Ipsen, Exelixis, Roche/Genentech. M.B. Atkins: Consulting or advisory role: Roche/Genentech, Pfizer, Novartis, X4 Pharma, Bristol-Myers Squibb, Nektar, Merck, Exelixis, Acceleron Pharma, Peleton, Eisai, Celldex, Alexion Pharmaceuticals, AstraZeneca/MedImmune, Glactone Pharma, Agenus, Idera, Argos Therapeutics, Array BioPharma, Boehringer Ingelheim, Aduro Biotech; Honoraria: Bristol-Myers Squibb. T.B. Powles: Consulting or advisory role: Roche/Genentech, Bristol-Myers Squibb, Novartis, Merck, AstraZeneca; Honoraria: Bristol-Myers Squibb, Roche/Genentech, Merck; Research funding: AstraZeneca/ MedImmune, Roche/Genentech. B.I. Rini: Consulting or advisory role: Corvus Pharmaceuticals, Pfizer, Merck; Honoraria: Bristol-Myers Squibb, Roche/Genentech, Merck; Travel, accommodations, expenses: Pfizer; Research funding: Pfizer, Bristol-Meyers Squibb, Merck, Roche/Genentech. R.J. Motzer: Consulting or advisory role: Pfizer, Novartis, Eisai, Exelixis, Roche/Genentech, Merck; Travel, accommodations, expenses: Bristol-Meyers Squibb; Research funding: Pfizer, Bristol-Meyers Squibb, GlaxoSmithKline, Novartis, Eisai, Roche/Genentech. S.K. Pal: Consulting role: Pfizer, Novartis, Aveo, Myriad, Genentech, Exelixis, BMS, Astellas, Ipsen, Eisai; Honoraria: Novartis, Medivation, Astellas; Research funding: Medication. L. Fong: Research funding to institution: Roche/Genentech. U. De Giorgi: Personal fees: Astellas, Bristol Myers Squibb, Janssen, Ipsen, Pfizer, Pierre-Fabre, Sanofi; Non-financial support: Astellas, Bristol Myers Squibb. Y. Wang, F. Di Nucci, C. Kaiser, D. Tayama: Employee of Roche/Genentech. T. Khaznadar: Employee of Roche. F. Donskov: Research funding: Novartis, Pfizer, Ipsen. All other authors have declared no conflicts of interest.