Atezolizumab (atezo) + bevacizumab (bev) versus sunitinib (sun) in pts with untreated metastatic renal cell carcinoma (mRCC) and sarcomatoid (sarc) histology: IMmotion151 subgroup analysis.

Authors

Brian Rini

Brian I. Rini

Cleveland Clinic Taussig Cancer Institute, Cleveland, OH

Brian I. Rini , 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

Organizations

Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, Memorial Sloan Kettering Cancer Center, New York, NY, Barts Cancer Institute, Queen Mary University of London, Royal Free NHS Trust, London, United Kingdom, Beth Israel Deaconess Medical Center, Boston, MA, Gustave Roussy, Villejuif, France, Department of Oncology, Aarhus University Hospital, Aarhus, Denmark, The Christie NHS Foundation Trust, Manchester, United Kingdom, Azienda Ospedaliera S.Maria, Terni, Italy, Department of Urology, University of Tübingen, Tubingen, Germany, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy, IRCCS San Matteo University Hospital Foundation, Pavia, Italy, CHU Hopitaux de Bordeaux-Hôpital Saint-André, Bordeaux, France, Ashford Cancer Centre Research, Kurralta Park, SA, Australia, MD Anderson Cancer Center Madrid, Madrid, Spain, Genentech, Inc., San Francisco, CA, Genentech, Inc., South San Francisco, CA, Genetech Inc, South San Francisco, CA, Georgetown Lombardi Comprehensive Cancer Center, Washington, DC

Research Funding

Pharmaceutical/Biotech Company

Background: In the Phase 3 IMmotion151 trial, atezo + bev showed improved PFS vs sun in untreated mRCC pts expressing PD-L1. Here we report results of a prespecified subgroup analysis in pts whose tumors have sarc histology, an independent predictor of poor survival. Methods: Pts were randomized to receive atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w or sun 50 mg po qd for 4w on, 2w off. Coprimary endpoints were reported previously (Motzer ASCO GU 2018). Secondary endpoints included INV-PFS and OS in sarc pts and are shown here with INV-ORR, safety, PRO and biomarker data. Results: 142 randomized pts (16%) from IMmotion151 had tumors with any component of sarc histology; mPFS was 8.3 vs 5.3 mo with atezo + bev vs sun and mOS was NR vs 15.0 mo, respectively (see Table for PD-L1+). ORR was 49% vs 14% and CR rate was 10% vs 3% in the atezo + bev vs sun arms. Grade 3-4 AEs occurred in 27 pts (40%) with atezo + bev and 34 (49%) with sun. Using the MDASI scale, sarc pts reported longer median time to deterioration (TTD) of symptom interference with daily activities with atezo + bev vs sun (11.3 vs 4.9 mo). Prevalence of AngiogenesisHigh gene expression (GE) signature subset was lower (34% vs 65%) and T-effectorHigh 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%). Conclusions: mRCC pts with sarc histology had longer OS and PFS and a higher ORR/CR rate when treated with atezo + bev vs sun, regardless of PD-L1 status. Biomarker data support a biological correlate for the increased responsiveness to atezo + bev in sarc pts. Clinical trial information: NCT02420821

All Sarc
PD-L1+ Sarc
Atezo + Bev
n = 68
Sun
n = 74
Stratified HRAtezo + Bev
n = 36
Sun
n = 50
Stratified HR
mPFS, mo8.35.30.528.65.60.45
(5.4, 12.9)(3.3, 6.7)(0.34, 0.79)(3.9, 15.3)(3.3, 6.7)(0.26, 0.77)
mOS, moNR15.00.56NR15.00.53
(18.3, NR)(8.7, NR)(0.32, 0.96)(17.1, NR)(8.4, NR)(0.27, 1.06)
12-mo OS, %69607161
(58, 81)(48, 71)(56, 86)(47, 75)
ORR, %49145612
(36, 61)(7, 23)(38, 72)(5, 24)
CR, %103144
TTD MDASI, mo11.34.90.61
(6.3, 17.5)(3.5, 7.6)(0.33, 1.11)

m, median NR, not reached Parentheses denote 95% CI Stratification factors: MSKCC risk score, liver mets, PD-L1 status

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Abstract Details

Meeting

2019 ASCO Annual Meeting

Session Type

Poster Discussion Session

Session Title

Genitourinary (Nonprostate) Cancer

Track

Genitourinary Cancer—Kidney and Bladder

Sub Track

Kidney Cancer

Clinical Trial Registration Number

NCT02420821

Citation

J Clin Oncol 37, 2019 (suppl; abstr 4512)

DOI

10.1200/JCO.2019.37.15_suppl.4512

Abstract #

4512

Poster Bd #

338

Abstract Disclosures