Abstract 2887
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.
| Table. IMpower130 Efficacy Analyses | |||
|
| Arm A | Arm B | |
| ITT-WT | n=451 | n=228 | |
| Median 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=447 | n=226 | |
| Confirmed ORR (investigator assessed) (95% CI) | 49.2% (44.49–53.96) | 31.9% (25.84–38.36) | |
|
| n=220 | n=72 | |
| Median DOR (95% CI) | 8.4 mo (6.9–11.8) | 6.1 mo (5.5–7.9) | |
|
| |||
| PD-L1 higha | n=88 | n=42 | |
| Median 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 lowa | n=128 | n=65 | |
| Median 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 negativea | n=235 | n=121 | |
| Median 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) | ||
|
| |||
| ITT | n=483 | n=240 | |
| Median 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. | |||
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.
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.
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