Abstract 1271P
Background
Atezo (anti–PD-L1) showed overall survival (OS) benefit over doc in the phase II (POPLAR; N=287) and phase III (OAK; N=1225) studies in patients (pts) with advanced NSCLC. 4-year survival analysis from both studies is reported for the first time.
Methods
In both studies, pts were randomised 1:1 to receive atezo (1200 mg) or doc (75 mg/m2) IV Q3W; PD-L1 expression was assessed by the Ventana SP142 assay on tumour cells (TC) and tumour-infiltrating immune cells (IC); landmark OS was estimated by the Kaplan-Meier method.
Results
The minimum follow-up was 53 (POPLAR) and 45 (OAK) mo − an additional 17 and 19 mo follow-up, respectively, from prior reports. 4-year survival rates with atezo vs doc were 14.8% vs 8.1% and 15.5% vs 8.7% in POPLAR and OAK, respectively. The long-term OS benefit of atezo vs doc was seen across histology and PD-L1 expression subgroups. Of pts in the atezo arms who lived ≥4 years in POPLAR (N=15) and OAK (N=43), 40% and 23% were in the PD-L1–high (TC3 or IC3) subgroup, 33% and 37% were in the PD-L1–negative (TC0 and IC0) subgroup, and 87% and 88% had non-squamous histology, respectively. Among 4-year survivors in the doc arms, 2/4 (50%) and 17/26 (65%) received subsequent immunotherapy in POPLAR and OAK, respectively, vs 3/15 (20%) and 10/43 (23%) in the atezo arms. Fewer Grade 3-4 treatment (tx)-related adverse events (AEs) and AEs leading to tx withdrawal occurred in the atezo vs doc arms in both studies.
Conclusions
4-year OS rates favoured atezo vs doc regardless of histology and PD-L1 expression in both studies, despite a high rate of subsequent immunotherapy in the doc arm. The PD-L1–high subgroups continued to derive the greatest OS benefit with atezo vs doc; however, the PD-L1–negative subgroups also sustained an improved long-term OS benefit with atezo vs doc. Most pts in the doc arms received subsequent immunotherapy. Atezo tx was well tolerated, and safety was consistent with prior reports. Table: 1271P
4-yr landmark OS rates in POPLAR and OAK
| Population | 4-yr OS rate, % | |||||||
| POPLAR | OAK | |||||||
| N | Atezo % | Doc % | Δ% (95% CI) | N | Atezo % | Doc % | Δ% (95% CI) | |
| ITT | 287 | 14.8 | 8.1 | 6.7 (−1.1, 14.4) | 1225 | 15.5 | 8.7 | 6.8 (2.8, 10.8) |
| PD-L1 expression subgroups | ||||||||
| TC3 or IC3 | 47 | 33.3 | 14.9 | 18.4 (−5.8, 42.7) | 174 | 27.8 | 9.8 | 18.1 (6.1, 30.0) |
| TC2/3 or IC2/3 | 105 | 19.1 | 7.9 | 11.2 (−2.2, 24.6) | 350 | 19.9 | 11.9 | 8.0 (−0.6, 16.7) |
| TC1/2/3 or IC1/2/3 | 195 | 14.6 | 8.5 | 6.2 (−3.2, 15.5) | 684 | 16.8 | 11.8 | 5.0 (−0.8, 10.8) |
| TC0 and IC0 | 92 | 15.2 | 6.8 | 8.4 (−5.6, 55.4) | 531 | 13.9 | 5.1 | 8.7 (3.3, 14.2) |
| Histology subgroups | ||||||||
| Non-squamous | 190 | 18.6 | 10.0 | 8.6 (−1.7, 19.0) | 904 | 17.9 | 10.1 | 7.7 (2.8, 12.7) |
| Squamous | 97 | 7.0 | NE | NE | 321 | 8.5 | 4.8 | 3.7 (−2.4, 9.9) |
NE, not estimable. P values not presented due to small sample sizes.
Clinical trial identification
NCT01903993 (POPLAR), NCT02008227 (OAK).
Editorial acknowledgement
Medical writing assistance for this abstract was provided by Kshipra Desai, PhD 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
J. Mazieres: Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: Merck & Co.; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Hengruii; Advisory/Consultancy: Daiichi; Advisory/Consultancy: Boehringer; Advisory/Consultancy: Takeda. A. Rittmeyer: Advisory/Consultancy: AbbVie; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: BMS; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche. S.M. Gadgeel: Advisory/Consultancy: Genentech/Roche; Honoraria (self), Research grant/Funding (self), Travel/Accommodation/Expenses: Merck; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Takeda; Advisory/Consultancy: Novartis; Advisory/Consultancy: Daiichi Sankyo. T. Hida: Honoraria (self), Research grant/Funding (institution): Chugai Pharmaceuticals ; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution): Merck & Co. D. Gandara: Advisory/Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Institutional Contract: AstraZeneca; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Institutional Contract: Guardant Health; Advisory/Consultancy: Inviata; Advisory/Consultancy, Institutional Contract: IO Biotech; Advisory/Consultancy: OnoCyte. D. Cortinovis: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck & Co.; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca. F. Barlesi: Honoraria (self), Research grant/Funding (institution), Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Research grant/Funding (institution): Bayer; Honoraria (self), Research grant/Funding (institution), Non-remunerated activity/ies: BMS; Honoraria (self), Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (self), Research grant/Funding (institution): Eli Lilly Oncology; Honoraria (self), Research grant/Funding (institution), Non-remunerated activity/ies: Roche; Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution), Non-remunerated activity/ies: Merck; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution), Non-remunerated activity/ies: Pierre Fabre; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Takeda; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): ACEA; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Ipsen; Research grant/Funding (institution): Ignyta; Research grant/Funding (institution): Innate Pharma; Research grant/Funding (institution): Loxo; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): Sanofi-Aventis. W. Yu, C. Matheny, M. Ballinger: Full/Part-time employment: Genentech; Shareholder/Stockholder/Stock options: Roche. K. Park: Advisory/Consultancy: Roche.