136PD_PR 3-year survival and duration of response in randomized phase II study of atezolizumab (atezo) vs docetaxel (doc) in 2L+ NSCLC (POPLAR)

Abstract

Background: Atezo (anti–PD-L1) has demonstrated OS benefit over doc in a randomized Phase II study, POPLAR, in patients with advanced NSCLC. This benefit has been confirmed in the randomized Phase III study OAK (Rittmeyer, 2017). The 3-year survival analysis of the POPLAR study presented here describes the longest survival follow-up reported to date of an all-comer randomized PD-L1/PD-1 immunotherapy trial in 2L + NSCLC. Methods: Patients were randomized 1:1 to receive atezo (1200 mg) or doc (75 mg/m2) IV q3w. Tumors were prospectively evaluated for tumor cell (TC) or tumor-infiltrating immune cell (IC) PD-L1 expression using the VENTANA SP142 IHC assay. Landmark OS was estimated using the Kaplan-Meier method. Data cutoff, April 7, 2017; minimum follow-up, 3 years. Results: The 2-year and 3-year survival with atezo vs doc were 32.2% vs 16.6% and 18.7% vs 10.0%, respectively. The long-term OS benefit of atezo vs doc was observed across histology and PD-L1 expression subgroups (Table). While the TC3 or IC3 subgroup derived the greatest OS benefit, the TC0 and IC0 subgroup also had improved long-term OS with atezo vs doc. The ITT ORR was 15% in both atezo and doc arms, but the median duration of response was 3 times longer with atezo (22.3 months [95% CI: 11.6, 31.1] vs 7.2 months [95% CI: 5.8, 12.2] with doc). Seven of the 11 doc-arm 3-year survivors received subsequent non-protocol therapy with anti–PD-L1/PD-1 agents. Atezo had a favorable safety profile compared with doc that was consistent with previous reports.TableLandmark OS in the ITT, PD-L1 expression, and histology subgroups in POPLAR2-year OS rate, %3-year OS rate, %Population (n, atezo vs doc)AtezoDocPvalueaFor descriptive purpose only. TC3 or IC3 = PD-L1 ≥ 50% TC or 10% IC; TC2/3 or IC2/3 = PD-L1 ≥ 5% TC or IC; TC1/2/3 or IC1/2/3 = PD-L1 ≥ 1% TC or IC; TC0 and IC0 = PD-L1 < 1% TC and IC. NCT01903993.AtezoDocPvalueaFor descriptive purpose only. TC3 or IC3 = PD-L1 ≥ 50% TC or 10% IC; TC2/3 or IC2/3 = PD-L1 ≥ 5% TC or IC; TC1/2/3 or IC1/2/3 = PD-L1 ≥ 1% TC or IC; TC0 and IC0 = PD-L1 < 1% TC and IC. NCT01903993.ITT (144 vs 143)32.2%16.6%0.002718.7%10.0%0.0419PD-L1 Expression SubgroupsTC3 or IC3 (24 vs 23)41.7%19.9%0.100337.5%14.9%0.0724TC2/3 or IC2/3 (50 vs 55)36.1%13.8%0.008221.2%9.9%0.1166TC1/2/3 or IC1/2/3 (93 vs 102)36.0%19.8%0.012418.0%11.0%0.1759TC0 and IC0 (51 vs 41)25.0%6.8%0.020220.5%6.8%0.0693Histology SubgroupsNon-squamous (95 vs 95)32.2%21.1%0.096023.3%12.4%0.0585Squamous (49 vs 48)32.7%7.8%0.00209.4%5.2%0.4603a For descriptive purpose only. TC3 or IC3 = PD-L1 ≥ 50% TC or 10% IC; TC2/3 or IC2/3 = PD-L1 ≥ 5% TC or IC; TC1/2/3 or IC1/2/3 = PD-L1 ≥ 1% TC or IC; TC0 and IC0 = PD-L1 < 1% TC and IC. NCT01903993. Open table in a new tab Conclusions: Atezo demonstrates superior 2-year and 3-year OS benefit compared with doc, and this benefit is observed across histology and PD-L1 expression subgroups (including TC0 and IC0). Atezo is well tolerated, and responses are highly durable. These results are consistent with long-term OS results from OAK (Satouchi, WCLC 2017). Acknowledgement of contribution: M. Gandhi, W. Yu, C. Matheny, P. He, A. Sandler, M. Ballinger, Genentech, Inc., South San Francisco, CA, USA. Clinical trial identification: NCT01903993 Legal entity responsible for the study: F. Hoffmann-La Roche Ltd/Genentech, Inc. Funding: F. Hoffmann-La Roche Ltd/Genentech, Inc. Disclosure: K. Park: Consulting/Advisory Role: Astellas Pharma, AstraZeneca, Boehringer Ingelheim, Clovis Oncology, Lilly, Hanmi, Kyowa Hakko Kirin, Novartis, Ono Pharmaceutical, Roche. Speakers Bureau: Boehringer Ingelheim, Research Funding: AstraZeneca. C. Lewanski: Consultant: MSD, Roche, AstraZeneca. S. Gadgeel: Speaker's bureau- Astra-Zeneca, Genentech/Roche Advisory Boards: Astra-Zeneca, Ariad, Pfizer, Bristol Myers Squibb and Genentech/Roche. A. Rittmeyer: Grants as an advisor or speaker by: Astra Zeneca, BMS, Boehringer Ingelheim, Eli Lilly, Pfizer and Roche Genentech. A. Artal-Cortes: Advisory boards: Roche, BMS, MSD Travel fees: Roche. F. Braiteh: Speaking and consulting fees received From Genentech. M. Gandhi: Genentech employee and Roche stock. W. Yu: Genentech employee and Roche stock. C. Matheny: Genentech employee and Roche stock, Roche/Genentech travel, accommodations, expenses patents, royalties or other intellectual property: Stanford University (patient with Stanford, do not currently receive royalties or have other intellectual property). P. He: Genentech employee and Roche stock. A. Sandler: Genentech employee; Roche and Amgen stock, Husband has stocks for Allergan and Gilead. M. Ballinger: Genentech employee and Roche stock. All other authors have declared no conflicts of interest.