Bracarda, Sergio

Objective To evaluate patient‐reported outcome (PRO) data from the IMmotion150 study. The phase 2 IMmotion150 study showed improved progression‐free survival with atezolizumab plus bevacizumab vs sunitinib in patients with programmed death‐ligand 1 (PD‐L1)+ tumours and suggested activity of atezolizumab monotherapy in previously untreated metastatic renal cell carcinoma (mRCC). Patients and methods Patients with previously untreated mRCC were randomised to atezolizumab 1200 mg intravenously (i.v.) every 3 weeks ( n = 103), the atezolizumab regimen plus bevacizumab 15 mg/kg i.v. every 3 weeks ( n = 101), or sunitinib 50 mg orally daily (4 weeks on, 2 weeks off; n = 101). The MD Anderson Symptom Inventory (MDASI) and Brief Fatigue Inventory (BFI) were administered on days 1 and 22 of each 6‐week cycle. Time to deterioration (TTD), change from baseline in MDASI core and RCC symptom severity, interference with daily life, and BFI fatigue severity and interference scores were reported for all comers. The TTD was the first ≥2‐point score increase over baseline. Absolute effect size ≥0.2 suggested a clinically important difference with checkpoint inhibitor therapy vs sunitinib. Results Completion rates were >90% at baseline and ≥80% at most visits. Delayed TTD in core and RCC symptoms, symptom interference, fatigue, and fatigue‐related interference was observed with atezolizumab (both alone and in combination) vs sunitinib. Improved TTD (hazard ratio [HR], 95% confidence interval [CI]) was more pronounced with atezolizumab monotherapy: core symptoms, 0.39 (0.22–0.71); RCC symptoms, 0.22 (0.12–0.41); and symptom interference, 0.36 (0.22–0.58). Change from baseline by visit, evaluated by the MDASI, also showed a trend favouring atezolizumab monotherapy vs sunitinib. Small sample sizes may have limited the ability to draw definitive conclusions. Conclusion PROs suggested that atezolizumab alone or with bevacizumab maintained daily function compared with sunitinib. Notably, symptoms were least severe with atezolizumab alone vs sunitinib (IMmotion150; ClinicalTrials.gov Identifier: NCT01984242).

4515 Background: The phase 2 IMmotion150 study showed improved PFS with atezo + bev vs sun in patients (pts) whose tumors were PD-L1+ and corroborated the activity of atezo monotherapy in previously untreated mRCC. This study offers an opportunity to evaluate PROs with immunotherapy and VEGF-directed therapy alone and in combination. Methods: Pts randomized to atezo 1200 mg IV q3w alone or with bev 15 mg/kg IV q3w, or sun 50 mg po qd for 4 wk on/2 wk off completed the MD Anderson Symptom Inventory (MDASI) and Brief Fatigue Inventory (BFI) q3w of each 6-wk cycle until progression (RECIST 1.1). Time to deterioration (TTD; first ≥ 2-point score increase over baseline [BL]) and change from BL (effect size [ES] ≥ 0.2 suggests a clinically important difference vs sun) in MDASI symptom severity and interference and BFI fatigue severity and interference scores are reported for all-comers. Results: Completion rates were > 90% at BL and ≥ 80% at most visits across arms. BL PRO scores indicating mild symptoms and interference were similar across arms. Delayed TTD of symptom severity and interference with daily life was seen with atezo vs sun and atezo + bev vs sun and was longest with atezo alone (Table). Pts reported milder symptoms and less interference during the first 6 cycles with atezo vs sun: ES mean (range) was 0.36 (0.07-0.68) for core symptom severity and 0.36 (0.04-0.83) for symptom interference. The 5 worst pt-reported symptoms during tx (dry mouth, fatigue, rash, drowsiness, lack of appetite) were all in the sun arm; all 16 symptoms measured were milder with atezo vs sun. Conclusions: PROs suggest that atezo alone or with bev maintained daily function with minimal symptom interference vs sun. Clinical activity, safety and PRO data for atezo support its investigation in adjuvant tx of high-risk RCC pts (IMmotion010; NCT03024996). Clinical trial information: NCT01984242. [Table: see text]

4505 Background: While inhibiting VEGF improves outcomes in mRCC pts, most develop resistance, often within a year. Here, we report results from a Ph II study of atezo (anti–PD-L1) and bev (anti-VEGF) vs and following atezo or sun (TKI) in mRCC pts. Methods: Pts with untreated mRCC were enrolled in the hypothesis generating IMmotion150 study (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. After progression on atezo or sun, crossover to atezo + bev was allowed. PD-L1 status was scored on tumor-infiltrating immune cells (IC, SP142 IHC assay). The primary analysis was modified prior to final analysis to reflect the coprimary endpoints of IRF-assessed PFS (RECIST v1.1) in ITT pts and pts with PD-L1 expression on ≥ 1% of IC (PD-L1+). Results: 54% of pts were PD-L1+. In PD-L1+ pts 1L treatment resulted in a PFS hazard ratio (HR) of 0.64 for atezo + bev vs sun (table). After 1L treatment, 78% of sun and 60% of atezo pts who progressed subsequently received atezo + bev and achieved ORRs of 28% and 24%, respectively (table). Safety was comparable to the known individual profiles of atezo and bev. Additional clinical, safety and biomarker data will be presented. Conclusions: Atezo + bev resulted in encouraging antitumor activity in 1L pts with PD-L1+ mRCC. Preliminary activity in the 2L setting was demonstrated in pts who crossed over to atezo + bev, regardless of prior therapy. 1L atezo + bev vs sun is being evaluated in the ongoing Ph III study IMmotion151 (NCT02420821). Clinical trial information: NCT01984242. [Table: see text]

431 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. [Table: see text]