IMpower150: An exploratory analysis of efficacy outcomes in patients with EGFR mutations
Authors: M. Reck, R. Jotte, T.S.K. Mok, D.W.-T. Lim, F. Cappuzzo, F. Orlandi, D. Stroyakovskiy, N. Nogami, D. Rodríguez-Abreu, D. Moro-Sibilot, C.A. Thomas, F. Barlesi, G. Finley, M. Nishio, A. Lee, G. Shankar, W. Yu, M.A. Socinski
Journal: Annals of Oncology (2019)

Background: 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. The purpose of this analysis is to focus on the efficacy of atezo and/or bev with chemo in pts with EGFR mutations (EGFR-mt). Methods: 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. Primary endpoints were OS and INV-assessed PFS in the ITT–wild-type population (pts with no EGFR or ALK genomic alterations). Exploratory analyses included OS and INV-assessed PFS in pts with EGFR-mt disease, pts with sensitising EGFR-mt and pts with EGFR-mt disease with prior TKI therapy. Results: These data represent ≥ 20-mo follow-up (data cutoff: 22 Jan 2018) in the ITT population. 124 pts were EGFR-mt; 91 with a sensitising mutation. Baseline characteristics of EGFR-mt pts across 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-mts (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 and ITT populations. Conclusions: 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. Clinical trial identification: NCT02366143. Editorial acknowledgement: Medical writing assistance for this abstract was provided by Jessica Men, PharmD, of Health Interactions and funded by F. Hoffmann-La Roche, Ltd. Legal entity responsible for the study: F. Hoffmann-La Roche, Ltd. Funding: F. Hoffmann-La Roche, Ltd. Disclosure: M. Reck: Speakers bureau, consulting, advisory role: Roche, Lilly, Pfizer, BI, AZ, MSD, BMS, Merck, Novartis, Celgene; Other (support of parent study, funding of editorial support): Roche. R. Jotte: Speakers bureau; travel, accommodations, expenses: Bristol-Myers Squibb; Other (support of parent study, funding of editorial support): Roche. T.S.K. Mok: Honoraria, consult/ad role, research: AZ, BI, BMS, Merck, NVS, Pfizer, Roche/GNE; Honoraria, consult/ad role: LLY; Consult/Ad Role: ACEA, Celgene, geneD, Ignyta, OGXI, Vertex; Consult/ad role, research: Clovis, SFJ; Research: Eisai, Taiho; Stock: Sanomics, Hutch. D.W-T. Lim: Honoraria: AZ, BI, Novartis, MSD, Pfizer, Roche, Takeda, Taiho; Research grants (institution): BMS; Stock: Clearbridge Biomedics Pte Ltd, Mesh Bio Pte Ltd; Other (support of parent study, funding of editorial support): Roche. F. Cappuzzo: Speakers/Advisory board: Roche, AZ, BMS, Pfizer, MSD, Takeda; Other (support of parent study, funding of editorial support): Roche. F. Orlandi: Consult/ad role: AZ, Lilly; Consult/ad role, travel, research: Roche, BMS, MSD; Consult/ad role, travel: Pfizer; Speaker, travel, research: MedImm; Research: Amgen, BI, Astellas, Celltrion. D. Stroyakovskiy, C.A. Thomas: Support of parent study, funding of editorial support: Roche. N. Nogami: Honoraria: AZ, Pfizer, Ono Pharmaceutical, Kyowa Hakko Kririn, Taiho, Chugai, Eli Lilly, BI, MSD; Other (support of parent study and funding of editorial support): Roche. D. Rodríguez-Abreu: Speakers bureau: MSD, Roche, BMS, AZ, Pfizer; Other (support of parent study and funding of editorial support): Roche. D. Moro-Sibilot: Honoraria; Consulting/advisory role, travel, accommodations, expenses: Roche, MSD, Pfizer, BMS, AZ; Honoraria, consulting/advisory role: Novartis, Lilly; Other (support of parent study, funding of editorial support): Roche. F. Barlesi: Support of parent study, funding of editorial support: Roche; Personal fees: AZ, BMS, BI, Clovis, Lilly, Roche, Novartis, Merck, MSD, Pierre Fabre, Pfizer, Takeda; Consulting/advisory: MSD, Takeda. G. Finley: Speakers: BMS, BI, Astellas Medivation, Merck; Support of parent study, funding of editorial support: Roche. M. Nishio: Speakers/Ad board, research grant: Ono Pharma, BMS, Pfizer, Chugai, Lilly, Taiho, AZ, MSD, Novartis; Speakers/Ad board: BI, Sankyo, Merck; Research Grant: Astellas; Support of parent study, funding of editorial support: Roche. A. Lee: Employee/Stock: Genentech; Support of parent study, funding of editorial support: Roche. G. Shankar, W. Yu: Employee: Genentech; Support of parent study, funding of editorial support: Roche. M.A. Socinski: Honoraria/speakers bureau/research funding: Genentech; Support of parent study, funding of editorial support: Roche.Table104OmOS, moHR (95% CI)ABCPACPBCPABCP vs BCPACP vs BCPEGFR-mtNE n = 3421.4 n = 4518.7 n = 450.61 (0.29, 1.28)0.93 (0.51, 1.68) Sensitising EGFR mutationaNE n = 2621.2 n = 3317.5 n = 320.31 (0.11, 0.83)0.90 (0.47, 1.74)Received prior TKI therapyNE n = 2214.0 n = 2817.5 n = 280.39 (0.14, 1.07)1.05 (0.53, 2.09)mPFS, moHR (95% CI)EGFR-mt10.2 n = 346.9 n = 456.9 n = 450.61 (0.36, 1.03)1.14 (0.73, 1.78) Sensitising EGFR mutationaSensitising EGFR mutations are defined as exon 19 deletions or L858R mutations. NE, not estimable.10.3 n = 266.0 n = 336.1 n = 320.41 (0.23, 0.75)1.01 (0.61, 1.70)Received prior TKI therapy9.7 n = 225.7 n = 286.1 n = 280.42 (0.22, 0.80)1.24 (0.72, 2.15)a Sensitising EGFR mutations are defined as exon 19 deletions or L858R mutations. NE, not estimable. Open table in a new tab