Atezolizumab (atezo; anti–PD-L1) inhibits PD-L1 to restore anticancer immunity; bevacizumab (bev) may enhance atezo efficacy by inhibiting VEGF immunosuppression and promoting T-cell tumour infiltration. Atezo + bev + chemotherapy (chemo) prolonged PFS and OS vs bev + CP in pts with first-line nonsquamous NSCLC in the randomised Ph III IMpower150 study, including pts with EGFR or ALK genomic alterations. Here, we further analyse the efficacy of atezo and/or bev with chemo in pts with EGFR mutations (EGFR-mt) in this study.
The 1202 enrolled pts received atezo (A) 1200 mg + bev (B) 15 mg/kg + carboplatin (C) AUC 6 + paclitaxel (P) 200 mg/m2 (ABCP) or A + C + P (ACP) or B + C + P (BCP) by IV q3w for 4 or 6 cycles per investigator (INV) decision, then q3w maintenance with atezo + bev, atezo or bev, respectively. Co-primary endpoints were OS and INV-assessed PFS in the ITT–wild-type population (excluded pts with EGFR or ALK genomic alterations). Exploratory analyses included OS and INV-assessed PFS in pts with EGFR-mt disease, pts with sensitising EGFR mutations and pts with EGFR-mt disease who had prior TKI therapy.
These data represent ≥ 20-mo follow-up (data cutoff: 22 Jan 2018) in the ITT population. 124 pts were EGFR-mt, including 91 with a sensitising mutation. Baseline characteristics of EGFR-mt pts across the treatment arms were generally comparable to the ITT population. OS was improved with ABCP vs BCP in EGFR-mt pts, especially in pts with sensitising EGFR mutations (HR, 0.31 [95% CI: 0.11, 0.83]). This benefit extended to PFS (HR, 0.41 [95% CI: 0.23, 0.75]). See table for full efficacy results. Safety was similar between the EGFR-mt subgroup and the ITT population.
IMpower150 is the first randomised Ph III trial of a checkpoint inhibitor to show a benefit in pretreated EGFR-mt pts. Adding atezo to standard-of-care bev and chemo provided survival benefit in EGFR-mt pts who have failed TKIs, for whom this regimen may represent a new treatment option. Sensitising EGFR mutations are defined as exon 19 deletions or L858R mutations. NE, not estimable.mOS, mo HR (95% CI) ABCP ACP BCP ABCP vs BCP ACP vs BCP EGFR-mt NE n = 34 21.4 n = 45 18.7 n = 45 0.61 (0.29, 1.28) 0.93 (0.51, 1.68) Sensitising EGFR mutationa NE n = 26 21.2 n = 33 17.5 n = 32 0.31 (0.11, 0.83) 0.90 (0.47, 1.74) Received prior TKI therapy NE n = 22 18.4 n = 27 17.5 n = 28 0.39 (0.14, 1.07) 0.99 (0.49, 1.98) mPFS, mo HR (95% CI) EGFR-mt 10.2 n = 34 6.9 n = 45 6.9 n = 45 0.61 (0.36, 1.03) 1.14 (0.73, 1.78) Sensitising EGFR mutationa 10.3 n = 26 6.0 n = 33 6.1 n = 32 0.41 (0.23, 0.75) 1.01 (0.61, 1.70) Received prior TKI therapy 9.7 n = 22 5.7 n = 27 6.1 n = 28 0.42 (0.22, 0.80) 1.20 (0.69, 2.09)
Jessica Bessler of Health Interactions, funded by F. Hoffmann-La Roche.
NCT02366143.
F. Hoffmann-La Roche.
F. Hoffmann-La Roche.
T.S.K. Mok: Honor/Speaker B: AZ, BI, Roche, Pfizer, Lilly, Merck, MSD, Novartis, SFJ, ACEA, Vertex, BMS, geneDecode, OncoGenex, Celgene, Ignyta, Cirina, Fishawack, Sanomics*, Janssen, Takeda, Chi-Med*, OrigiMed, Hengrui, Sanofi, Yuhan(*Stock) Employee: CUHK. M.A. Socinski: Honoraria, Speakers\' bureau, Research Funding Genentech. M. Reck: Advisor/Board member: Lilly, Roche, BI, BMS, MSD, AstraZeneca, Merck, Novartis, Pfizer, Celgene; Speakers’ bureau: Roche, Lilly, Pfizer, BI, AstraZeneca, MSD, BMS, Merck, Novartis, Pfizer, Celgene. R.M. Jotte: Speakers\' bureau, Travel and accommodation expenses, Honoraria: Bristol-Myers Squibb. F. Cappuzzo: Speakers or advisory board: Roche, AZ, BMS, Pfizer, MSD, Takeda. F.J. Orlandi: Consulting/advisory role: AZ, Roche, BMS, MSD, Lilly, Pfizer Travel and accommodation expenses: Pfizer, MSD, AZ, Roche, BMS; Research Funding AZ, Amgen, Roche, BI, Astellas Medivation, MSD, BMS, Celltrion; Speakers: AstraZEneca. N. Nogami: Honoraria: AstraZeneca, Pfizer Inc., Ono Pharmaceutical CO., Ltd., Kyowa Hakko Kirin, Taiho Phamaceutical Co.,Ltd., Chugai Pharmaceutical Co., Ltd, Eli Lilly Japan, Boehringer Ingelheim, MSD KK. D. Rodríguez-Abreu: Speakers\' bureau: MSD, Roche, BMS, AstraZeneca, Pfizer. D. Moro-Siblot: Honoraria, consulting/advisory role: Roche, MSD, Pfizer, Novartis, BMS, AstraZeneca, Lilly; Travel and accommodation expenses: Roche, MSD, Pfizer, BMS, AstraZeneca. F. Barlesi: Personal fees: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Clovis Oncology, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer. G. Finley: Promotional speaking: Bristol Meyers, Boehringer Ingleheim, Astellas Medivation, Merck. A. Lee: Employee, owner of stock: Genentech. G. Shankar, W. Yu: Employee: Genentech. M. Kowanetz: Genentech Employee with Roche Stock. Patent biomarkers and methods of treating PD-1 and PD-l1 related conditions pending. W. Lin: Employee: Genentech; Stock owner: Roche. M. Nishio: Speakers/advisory: Ono Pharma, BMS, Pfizer, Chugai Pharma, Lilly, Taiho Pharma, AZ, BI, MSD, Novartis, Daiichi Sankyo, Merck Serono; Research Funding MSD, Novartis, Ono Pharma, Chugai Pharma, BMS, Taiho Pharma, Lilly, AZ, Pfizer, Astellas. All other authors have declared no conflicts of interest.