Abstract CT076: IMpower150: Efficacy of atezolizumab (atezo) plus bevacizumab (bev) and chemotherapy (chemo) in 1L metastatic nonsquamous NSCLC (mNSCLC) across key subgroups
Authors: Kowanetz Marcin , Socinski Mark A. , Zou Wei , McCleland Mark , Yang Nancy , Chavez Ariel Lopez , Spira Alexander , Mazières Julien , Braiteh Fadi , Shames David , Sandler Alan , Reck Martin 
Published: August 2018

Introduction: Atezo (anti-PD-L1) + bev + chemo prolonged PFS vs bev + chemo in patients (pts) with 1L non-squamous mNSCLC in the randomized Ph 3 IMpower150 study regardless of PD-L1 expression. This analysis aims to further understand the efficacy of atezo + bev + chemo in key subgroups: PD-L1 expression subgroups defined by the SP142 and SP263 IHC assays, patients with EGFR/ALK genetic alterations and patients with liver metastases at baseline.

Methods: Pts received atezo 1200 mg + bev 15 mg/kg + carboplatin (C) AUC 6 + paclitaxel (P) 200 mg/m2 (Arm B) or bev + C + P (Arm C) IV q3w. A co-primary endpoint (EP) was PFS in the ITT-WT (EGFR or ALK wild-type pts); a secondary EP was PFS in subgroups defined by PD-L1 expression on tumor cells (TC) and tumor-infiltrating immune cells (IC) with SP142. Retrospective analysis with SP263 was a prespecified exploratory EP.

Results: In Arms B and C of the ITT-WT (n = 692), 503 pts had available tumor sections for SP263 testing (BEP). Pt characteristics in the ITT-WT and BEP were similar. A similar PFS benefit was observed for Arm B vs C across all PD-L1 expression subgroups defined by either assay, including pts with PD-L1-negative and PD-L1-low tumors (Table). PFS benefit with Arm B vs C was also observed in patients with EGFR or ALK genomic alterations, including patients with actionable EGFR mutations, and in patients with liver metastases at baseline (Table).

Conclusion: PFS benefit with atezo + bev + chemo was observed across all PD-L1 subgroups, regardless of the IHC assay used. Additionally, clinically meaningful PFS benefit was observed in patients with EGFR/ALK genomic alterations, and in patients with liver metastases with this combination.

Table. PFS in Biomarker Subgroups and Other Subgroups of Interest in IMpower150Median PFS, moPFSan (%)HRb (95% CI)P ValueArm BArm CITT-WT692 (100%)0.62 (0.52, 0.74)&lt;0.00018.36.8BEP with SP263 results in ITT-WT503 (73%)0.62 (0.50, 0.76)&lt;0.00018.36.8PD-L1 Expression Subgroups Defined by the VENTANA SP142 Assay (BEP, n=503)PD-L1 negative TC0 and IC0235 (47%)0.77 (0.57, 1.04)0.08368.27.0PD-L1 low TC1/2 or IC1/2167 (33%)0.53 (0.37, 0.76)0.00058.36.1PD-L1 high TC3 or IC3101 (20%)0.49 (0.30, 0.79)0.003211.16.9PD-L1 Expression Subgroups Defined by the VENTANA SP263 IHC Assay (BEP, n=503)PD-L1 negative TC &lt; 1%237 (47%)0.72 (0.53, 0.97)0.02987.27.0PD-L1 low TC &lt; 50% and ≥ 1%140 (28%)0.57 (0.38, 0.84)0.00419.76.9PD-L1 high TC ≥ 50%126 (25%)0.50 (0.33, 0.77)0.00159.16.2Other Subgroups of Interest (ITT, n=800)ITT800 (100%)0.61 (0.52, 0.72)&lt;0.00018.36.8EGFR/ALK+c108 (14%)0.59 (0.37, 0.94)0.02539.76.1EGFR exon 19 deletion of L858R59 (7%)0.41 (0.22, 0.78)0.005010.26.1Liver metastases110 (14%)0.40 (0.26, 0.62)&lt;0.00018.25.4No liver metastases690 (86%)0.64 (0.53, 0.76)&lt;0.00018.37.0BEP, biomarker-evaluable population; IC, tumor-infiltrating immune cell; IHC, immunohistochemistry; PD-L1, programmed death-ligand 1; TC, tumor cell; WT, wild type. TC0 and IC0 = PD-L1 expression on &lt; 1% of TC or IC; TC1/2 or IC1/2 = PD-L1 expression on &lt; 50% and ≥ 1% of TC or &lt; 10% of and ≥ 1% of IC; TC3 or IC3 = PD-L1 expression on ≥ 50% of TC or ≥ 10% of IC. a Investigator assessed b Stratified HR for ITT-WT and ITT; unstratified HR for all other subgroups. c Patients with a sensitizing EGFR mutation or ALK rearrangement must have disease progression or intolerance of treatment with one or more approved targeted therapies. d Other EGFR mutations include L861Q, G719X, S7681, exon 20 insertion, T790M, and other. (NCT02366143)

Citation Format: Marcin Kowanetz, Mark A. Socinski, Wei Zou, Mark McCleland, Nancy Yang, Ariel Lopez Chavez, Alexander Spira, Julien Mazières, Fadi Braiteh, David Shames, Alan Sandler, Martin Reck. IMpower150: Efficacy of atezolizumab (atezo) plus bevacizumab (bev) and chemotherapy (chemo) in 1L metastatic nonsquamous NSCLC (mNSCLC) across key subgroups [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT076.