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
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 HR | Atezo + Bev n = 36 | Sun n = 50 | Stratified HR | |
mPFS, mo | 8.3 | 5.3 | 0.52 | 8.6 | 5.6 | 0.45 |
(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, mo | NR | 15.0 | 0.56 | NR | 15.0 | 0.53 |
(18.3, NR) | (8.7, NR) | (0.32, 0.96) | (17.1, NR) | (8.4, NR) | (0.27, 1.06) | |
12-mo OS, % | 69 | 60 | — | 71 | 61 | — |
(58, 81) | (48, 71) | (56, 86) | (47, 75) | |||
ORR, % | 49 | 14 | — | 56 | 12 | — |
(36, 61) | (7, 23) | (38, 72) | (5, 24) | |||
CR, % | 10 | 3 | — | 14 | 4 | — |
TTD MDASI, mo | 11.3 | 4.9 | 0.61 | — | — | — |
(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 Disclosures
2017 ASCO Annual Meeting
First Author: Michael B. Atkins
2018 Genitourinary Cancers Symposium
First Author: Robert J. Motzer
2018 Genitourinary Cancers Symposium
First Author: Robert J. Motzer
2023 ASCO Annual Meeting
First Author: Richard S. Finn