IMpower130: Progression-free survival (PFS) and safety analysis from a randomised phase III study of carboplatin + nab-paclitaxel (CnP) with or without atezolizumab (atezo) as first-line (1L) therapy in advanced non-squamous NSCLC

Background: Atezo (anti-PD-L1) monotherapy improves overall survival (OS) vs docetaxel in 2L+ NSCLC, regardless of PD-L1 status; phase 3, 1L studies have shown the clinical benefit of atezo plus chemotherapy. IMpower130 (NCT02367781) evaluated atezo + CnP vs CnP in patients (pts) with measurable (RECIST v1.1) stage IV non-squamous NSCLC. Methods: Pts (randomised 2:1) received atezo (1200 mg IV q3w) + CnP (carboplatin: AUC 6 q3w; nab-paclitaxel: 100 mg/m2 IV qw) (Arm A) or CnP (Arm B), for 4 or 6 21-day cycles and maintenance (Arm A: atezo until loss of clinical benefit; Arm B: best supportive care or pemetrexed q3w until disease progression [PD]). Crossover to atezo at PD was initially permitted for Arm B pts. Co-primary endpoints: investigator-assessed PFS and OS (ITT-WT population: EGFR-WT/ALK-negative). Secondary endpoints: OS and PFS (ITT population and by PD-L1 expression), response rate and safety. ITT population could be formally tested for OS/PFS if ITT-WT OS was positive. Results: 723 ITT (679 ITT-WT) pts were enrolled. Statistically significant, clinically meaningful improvements in OS and statistically significant improvements in PFS (ITT and ITT-WT) were observed in Arm A vs Arm B (table). PFS and OS benefit was observed in all PD-L1 subgroups, and consistently across all subgroups, except in pts with liver metastases and EGFR/ALK genomic alterations. In treated pts, 73.2% (Arm A) vs 60.3% (Arm B) had grade 3–4 treatment-related adverse events. Conclusions: Overall, IMpower130 showed statistically significant, clinically meaningful improvements in OS and statistically significant improvements in PFS with atezo + CnP, vs CnP, in 1L, stage IV non-squamous NSCLC, in this predominantly ITT-WT population. No new safety signals were identified.Table: LBA53IMpower 130 efficacy analysesArm A Atezo + CnPArm B CnPITT-WTn = 451n = 228Median OS (95% CI)18.6 mo (16.0–21.2)13.9 mo (12.0–18.7)HR (95% CI; P value)0.79 (0.64–0.98; 0.033)12-mo OS (95% CI)63.1% (58.59–67.66)55.5% (48.89–62.17)Median PFS (95% CI)7.0 mo (6.2–7.3)5.5 mo (4.4–5.9)HR (95% CI; P value)0.64 (0.54–0.77; <0.0001)12-mo PFS (95% CI)29.1% (24.83–33.44)14.1% (9.37–18.76)n = 447n = 226Confirmed ORR (investigator assessed) (95% CI)49.2% (44.49–53.96)31.9% (25.84–38.36)n = 220n = 72Median DOR (95% CI)8.4 mo (6.9–11.8)6.1 mo (5.5–7.9)PD-L1 highaPD-L1 high (TC3 or IC3): Patients with PD-L1 expression in≥50% of tumour cells or≥10% of tumour-infiltrating immune cells; PD-L1 low (TC1/2 or IC1/2): Patients with PD-L1 expression in≥1% and <50% of tumour cells or≥1% and <10% of tumour-infiltrating immune cells; and PD-L1 negative (TC0 and IC0): Patients with PD-L1 expression in<1% of tumour cells and <1% of tumour-infiltrating immune cells. Data cut-off: 15 March 2018. Minimum follow up: 13 months. NCT02367781. DOR, duration of response; HR, hazard ratio; IC, immune cells; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; TC, tumour cells.n = 88n = 42Median OS (95% CI)17.4 mo (14.78–NA)16.9 mo (10.94–NA)HR (95% CI)0.84 (0.51–1.39)Median PFS (95% CI)6.4 mo (5.49–9.76)4.6 mo (3.22–7)HR (95% CI)0.51 (0.34–0.77)PD-L1 lowaPD-L1 high (TC3 or IC3): Patients with PD-L1 expression in≥50% of tumour cells or≥10% of tumour-infiltrating immune cells; PD-L1 low (TC1/2 or IC1/2): Patients with PD-L1 expression in≥1% and <50% of tumour cells or≥1% and <10% of tumour-infiltrating immune cells; and PD-L1 negative (TC0 and IC0): Patients with PD-L1 expression in<1% of tumour cells and <1% of tumour-infiltrating immune cells. Data cut-off: 15 March 2018. Minimum follow up: 13 months. NCT02367781. DOR, duration of response; HR, hazard ratio; IC, immune cells; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; TC, tumour cells.n = 128n = 65Median OS (95% CI)23.7 mo (18.63–NA)15.9 mo (12.32–25.63)HR (95% CI)0.70 (0.45–1.08)Median PFS (95% CI)8.3 mo (7.16–10.35)6.0 mo (5.29–6.93)HR (95% CI)0.61 (0.43–0.85)PD-L1 negativeaPD-L1 high (TC3 or IC3): Patients with PD-L1 expression in≥50% of tumour cells or≥10% of tumour-infiltrating immune cells; PD-L1 low (TC1/2 or IC1/2): Patients with PD-L1 expression in≥1% and <50% of tumour cells or≥1% and <10% of tumour-infiltrating immune cells; and PD-L1 negative (TC0 and IC0): Patients with PD-L1 expression in<1% of tumour cells and <1% of tumour-infiltrating immune cells. Data cut-off: 15 March 2018. Minimum follow up: 13 months. NCT02367781. DOR, duration of response; HR, hazard ratio; IC, immune cells; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; TC, tumour cells.n = 235n = 121Median OS (95% CI)15.2 mo (12.88–19.15)12.0 mo (8.97–17.71)HR (95% CI)0.81 (0.61–1.08)Median PFS (95% CI)6.2 mo (5.52–7.16)4.7 mo (4.11–5.72)HR (95% CI)0.72 (0.56–0.91)ITTn = 483n = 240Median OS (95% CI)18.1 mo (15.3–20.8)13.9 mo (12.0–18.2)HR (95% CI; P value)0.80 (0.65–0.99; 0.039)Median PFS (95% CI)7.0 mo (6.3–7.3)5.6 mo (4.5–5.9)HR (95% CI; P value)0.65 (0.54–0.77; <0.0001)a PD-L1 high (TC3 or IC3): Patients with PD-L1 expression in ≥ 50% of tumour cells or ≥ 10% of tumour-infiltrating immune cells; PD-L1 low (TC1/2 or IC1/2): Patients with PD-L1 expression in ≥ 1% and <50% of tumour cells or ≥ 1% and <10% of tumour-infiltrating immune cells; and PD-L1 negative (TC0 and IC0): Patients with PD-L1 expression in < 1% of tumour cells and <1% of tumour-infiltrating immune cells. Data cut-off: 15 March 2018. Minimum follow up: 13 months. NCT02367781. DOR, duration of response; HR, hazard ratio; IC, immune cells; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; TC, tumour cells. Open table in a new tab Clinical trial identification: NCT02367781 (20 February 2015). Editorial acknowledgement: Support for third-party writing assistance for this abstract, furnished by Islay Steele, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Legal entity responsible for the study: F. Hoffmann-La Roche Ltd. Funding: F. Hoffmann-La Roche Ltd. Disclosure: F. Cappuzzo: Membership of advisory board: Roche, AstraZeneca, BMS, Pfizer, MSD. A. Morabito: Membership of advisory board: Astra Zeneca, Boehringer Ingelheim, MSD, Pfizer; Speaker bureaus: Boehringer Ingelheim, BMS, Amag, Incyte, Heron. A. Rittmeyer: Grants: AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD, Pfizer, Roche outside the submitted work. H-G. Kopp: Membership of advisory board: Roche, MSD, BMS. A. Zer: Membership of advisory board: AstraZeneca, Lilly, Boehringer Ingelheim. N. Reinmuth: Membership of advisory board: Roche, BMS, Astra Zeneca, MSD. V. Archer: Employee of Roche Products Limited. T. Ochi Lohmann: Employee of F. Hoffmann-La Roche. L. Wang, M. Kowanetz, W. Lin, A. Sandler: Employee of Genentech, Inc. H. West: Personal fees: AstraZeneca, Genentech/Roche, Pfizer (during the conduct of the study); Personal fees: Boehringer-Ingelheim (outside the submitted work). All other authors have declared no conflicts of interest.