LBA1_PRPrimary PFS and safety analyses of a randomized phase III study of carboplatin + paclitaxel +/− bevacizumab, with or without atezolizumab in 1L non-squamous metastatic nsclc (IMPOWER150)

Background: Atezolizumab (atezo; anti–PD-L1) inhibits PD-L1 binding to PD-1 and B7.1, restoring anti-cancer immunity. Bevacizumab (bev) may further enhance atezo efficacy by inhibiting VEGF immunosuppression and promoting T-cell tumour infiltration. IMpower150 evaluates the addition of atezo to carboplatin (C) + paclitaxel (P) ± bev in chemo-naive patients (pts) with nonsquamous (NSQ) mNSCLC. Methods: 1202 pts received atezo 1200 mg + C AUC 6 + P 200 mg/m2 (Arm A) or atezo + bev 15 mg/kg + C + P (Arm B) vs bev + C + P (Arm C) IV q3w for 4 or 6 cycles per investigator (INV) discretion, then maintenance atezo, atezo + bev or bev, respectively. Co-primary endpoints assessed at this data cutoff (15 Sep 2017; minimum follow up, 9.5 mo) were INV-assessed PFS in the ITT-WT (EGFR or ALK negative) population and in WT pts with expression of a tumour T-effector gene signature (Teff-WT; centrally assessed), and OS in the ITT-WT population, for the Arm B vs Arm C comparison. Due to pre-specified statistical testing hierarchy, Arm A vs Arm C has not been formally tested yet. Results: 356 pts in Arm B and 336 pts in Arm C were enrolled in the ITT-WT. Median age was 63 y; 60% were previous smokers (both arms). 61% and 62% were male, and 39% and 43% had ECOG PS 0 in Arms B and C, respectively. The HRs for INV-assessed PFS in Arm B vs C were 0.62 (95% CI: 0.52, 0.74; P < 0.0001) in the ITT-WT and 0.51 (0.38, 0.68; P < 0.0001) in the Teff-WT populations. Median PFS in Arm B vs C was 8.3 mo vs 6.8 mo and 11.3 mo vs 6.8 mo in the ITT-WT and Teff-WT populations, respectively. PFS benefit was seen regardless of PD-L1 IHC status, including PD-L1–negative pts (TC0/IC0; HR, 0.77 [95% CI: 0.61, 0.99]). Landmark PFS and ORR are shown (Table). Arm B had a comparable safety profile to Arm C; treatment-related serious AEs were 25% vs 19%, respectively.TableIMpower150 Primary PFS Analysis, Landmark PFS and ORRArm C (bev + C + P; N = 400)Arm B (atezo + bev + C + P; N = 400)ITT-WT population aWT populations exclude patients with EGFR or ALK driver mutations.n = 336n = 356Median PFS (95% CI), mo6.8 (6.0, 7.1)8.3 (7.7, 9.8)HR (95% CI; P value)0.62 (0.52, 0.74; P < 0.0001)ITT-WT landmark PFS (95% CI), % 6-month56% (51, 62)67% (62, 72) 12-month18% (13, 23)37% (31, 42)ORRb,Unconfirmed ORR.cn = 353 in Arm B and n = 331 in Arm C. (95% CI), %48% (43, 54)64% (58, 68)Teff-WT population aWT populations exclude patients with EGFR or ALK driver mutations.n = 129n = 155Median PFS (95% CI), mo6.8 (5.9, 7.4)11.3 (9.1, 13.0) HR (95% CI; P value)0.51 (0.38, 0.68; P < 0.0001)Teff-WT landmark PFS (95% CI), % 6-month57% (48, 66)72% (65, 79) 12-month18% (10, 25)46% (38, 54)ORRb,Unconfirmed ORR.dn = 153 in Arm B and n = 127 in Arm C. (95% CI), %54% (44, 62)69% (61, 76)HR, hazard ratio; ORR, objective response rate; PFS, progression-free survival; Teff, T-effector; WT, wild-type.a WT populations exclude patients with EGFR or ALK driver mutations.b Unconfirmed ORR.c n = 353 in Arm B and n = 331 in Arm C.d n = 153 in Arm B and n = 127 in Arm C. Open table in a new tab HR, hazard ratio; ORR, objective response rate; PFS, progression-free survival; Teff, T-effector; WT, wild-type. Conclusions: IMpower150 is the first Phase III study to show a statistically significant and clinically meaningful PFS benefit with atezo + bev + chemo vs bev + chemo in pts with 1L NSQ mNSCLC. Acknowledgement of contribution: G. Finley (Allegheny Cancer Center, Pittsburgh, PA, USA), R. Jotte (Rocky Mountain Cancer Centers, Denver, CO, USA), C. Kelsch, A. Lee, S. Coleman, Y. Shen, M. Kowanetz, A. Lopez-Chavez, A. Sandler (Genentech, Inc., South San Francisco, CA, USA). Clinical trial identification: NCT02366143 Legal entity responsible for the study: F. Hoffmann-La Roche Ltd/Genentech, Inc Funding: F. Hoffmann-La Roche Ltd/Genentech, Inc Disclosures: M. Reck: Consulting or Advisory Role: Lilly, F. Hoffmann-La Roche, BI, BMS, MSD, AstraZeneca, Merck, Novartis, Pfizer, Celgene. Speakers' Bureau: F. Hoffmann-La Roche, Lilly, Pfizer, BI, AstraZeneca, MSD, BMS, Merck, Novartis, Pfizer, Celgene. M. A. Socinski: Honoraria: Genentech, Speakers Bureau: Genentech, Research Funding: Genentech. F. Cappuzzo: Participation in advisory boards for Roche, AZ, BMS, Takeda, MSD, Lilly, Pfizer. F. Orlandi: Research grants from Astrazeneca, MSD, Genetech-Roche, Advisory tasks for AstraZeneca, Roche, Boehringer Ingelheim, Pfizer. N. Nogami: Honoraria: Meiji Seika Pharma Co., Ltd., AstraZeneca, Pfizer Inc., Bristol-Myers Squibb, ONO Pharmaceutical CO., LTD., Kyowa Hakko Kirin, Taiho Phamaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd, Eli Lilly Japan, Boehringer Ingelheim. D. Rodríguez-Abreu: Honoraria for lectures and Advisory Board from Bristol-Myers-Squibb, Merck Sharp & Dohme and Hoffmann-La Roche. D. Moro-Sibilot: Advisory boards for Roche, MSD, Pfizer, Novartis, BMS, Astra Zeneca, Lilly. F. Barlesi: Honarium from Genentech & Roche. G. Finley: Promotional speaking on behalf of Bristol Meyers, Boehringer Ingleheim, and Astellas Medivation, and Merck. C. Kelsch: Genentech Employee with Roche Stock. A. Lee: Genentech Employee with Roche Stock. S. Coleman: Genentech Employee with Roche Stock. Y. Shen: Genentech Employee with Roche Stock. M. Kowanetz: Genentech Employee with Roche Stock. A. Lopez-Chavez: Genentech Employee with Roche Stock. A. Sandler: Genentech Employee with Roche Stock. All other authors have declared no conflicts of interest.