Beth Israel Deaconess Medical Center, Boston, MA
David F. McDermott , Michael B. Atkins , Robert J. Motzer , Brian I. Rini , Bernard J. Escudier , Lawrence Fong , Richard Wayne Joseph , Sumanta K. Pal , Mario Sznol , John D. Hainsworth , Walter Michael Stadler , Thomas E. Hutson , Alain Ravaud , Sergio Bracarda , Cristina Suarez , Toni K. Choueiri , YounJeong Choi , Mahrukh A. Huseni , Gregg Daniel Fine , Thomas Powles
Background: While targeting VEGF improves outcomes for mRCC pts, resistance invariably develops, often within the first year. Here, we describe the efficacy and safety of atezo (anti-PD-L1) with bev (anti-VEGF) and atezo monotherapy vs sun (TKI) in first-line mRCC. Methods: Treatment-naïve mRCC pts were enrolled in a hypothesis generating Ph II study (IMmotion150; NCT01984242) and randomized to atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w, atezo alone or sun 50 mg PO QD 4 wk on/2 wk off. Crossover to atezo + bev after disease progression was allowed for pts receiving atezo or sun. PD-L1 expression was scored on tumor-infiltrating immune cells (IC, SP142 IHC assay). Coprimary endpoints were PFS (RECIST v1.1 by independent review [IRF]) in ITT pts and pts with PD-L1 expression on ≥ 1% of IC (PD-L1+). Results: Baseline characteristics were comparable across arms and between ITT and PD-L1+ pts. The majority of sun and atezo pts subsequently received atezo + bev. Median survival follow up was 20.7 mo. The PFS HR in ITT pts for atezo + bev vs sun was 1.00 and 1.19 for atezo vs sun. In PD-L1+ pts, the PFS HR for atezo + bev vs sun was 0.64 and 1.03 for atezo vs sun (table). Tx-related Gr 3-4 AEs were seen in 40%, 16% and 57% of pts in the atezo + bev, atezo and sun arms, respectively. AEs leading to death occurred in 3%, 2% and 2% of pts, respectively. Conclusion: Atezo + bev resulted in encouraging antitumor activity in the PD-L1+ subgroup of first-line RCC pts. Atezo + bev safety is consistent with the known profile of atezo and bev individually. The clinical benefit of atezo + bev vs sun will be evaluated in the ongoing Ph III study IMmotion151 (NCT02420821). Clinical trial information: NCT01984242
Atezo + Bev n = 101 | Atezo n = 103 | Sun n = 101 | Atezo + Bev vs Sun | Atezo vs Sun | |
---|---|---|---|---|---|
mPFSa, mo (95% CI) | HR (95% CI) | ||||
ITT N = 305 | 11.7 (8.4, 17.3) | 6.1 (5.4, 13.6) | 8.4 (7.0, 14.0) | 1.00 (0.69, 1.45) P = .982 | 1.19 (0.82, 1.71) P = .358 |
PD-L1+ n = 164 | 14.7 (8.2, 25.1) | 5.5 (3.0, 13.9) | 7.8 (3.8, 10.8) | 0.64 (0.38, 1.08) P = .095 | 1.03 (0.63, 1.67) P = .917 |
12-mo PFSa, % | |||||
ITT | 50 | 41 | 42 | - | - |
PD-L1+ | 52 | 37 | 34 | - | - |
ORRa (confirmed), n (%), 95% CI | |||||
ITT | 32 (32%) (23, 42) | 26 (25%) (17, 35) | 29 (29%) (20, 39) | - | - |
PD-L1+ | 23 (46%) (32, 61) | 15 (28%) (16, 42) | 16 (27%) (16, 40) | - | - |
a Assessed by IRF. P values for descriptive purposes only.
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Abstract Disclosures
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