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C.A. Thomas

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    Immunotherapy and next-generation TKIs: From second to frontline treatment (ID 55)

    • Event: ELCC 2018
    • Type: Poster Discussion session
    • Track:
    • Presentations: 1
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      134PD - Primary 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) (ID 469)

      07:45 - 09:00  |  Author(s): C.A. Thomas

      • Abstract
      • Slides

      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 non-squamous (NSQ) mNSCLC.

      1202 pts received atezo 1200 mg + C AUC 6 + P 200 mg/m[2] (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.

      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.Table:IMpower150 Primary PFS Analysis, Landmark PFS and ORR

      Arm C (bev + C + P; N = 400)Arm B (atezo + bev + C + P; N = 400)
      ITT-WT population[a]n = 336n = 356
      Median 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)
      ORR[b,c] (95% CI), %48% (43, 54)64% (58, 68)
      Teff-WT population[a]n = 129n = 155
      Median 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)
      ORR[b,d] (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.aWT populations exclude patients with EGFR or ALK driver mutations.bUnconfirmed = 353 in Arm B and n = 331 in Arm C.dn = 153 in Arm B and n = 127 in Arm C.

      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:

      Legal entity responsible for the study:
      F. Hoffmann-La Roche Ltd/Genentech, Inc

      F. Hoffmann-La Roche Ltd/Genentech, Inc

      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.

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