Presidential Symposium Proffered Paper session

LBA1 - IMpower133: Primary efficacy and safety + CNS-related adverse events in a phase I/III study of first-line (1L) atezolizumab + carboplatin + etoposide in extensive-stage SCLC (ES-SCLC)

Presentation Number
LBA1
Lecture Time
11:00 AM - 11:15 AM
Session Name
Speakers
  • Tony S.K. Mok
Location
Hall 406, Singapore, Singapore, Singapore
Date
24.11.2018
Time
11:00 AM - 12:30 PM
Authors
  • Tony S.K. Mok
  • Martin Reck
  • Leora Horn
  • Sivuonthanh Lam
  • David S. Shames
  • Juan Liu
  • Fairooz Kabbinavar
  • Wei Lin
  • Alan Sandler
  • Stephen V. Liu

Abstract

Background

1L standard-of-care treatment (tx) for ES-SCLC is platinum (carboplatin or cisplatin) + etoposide. Despite high response rates, outcomes remain poor. IMpower133, a global Ph1/3, double-blind, randomized, placebo (PBO)-controlled trial evaluated efficacy and safety of adding atezolizumab (atezo; anti–PD-L1) or PBO to 1L tx (NCT02763579).

Methods

Patient (pts) without prior tx for ES-SCLC were enrolled. PD-L1 testing was not required. Randomization was 1:1 to four 21-day cycles of carboplatin (AUC 5 mg/mL/min IV, Day 1) + etoposide (100 mg/m2 IV, Days 1–3) with either atezo (1200 mg IV, Day 1) or PBO, then maintenance atezo or PBO until PD, unacceptable toxicity or loss of clinical benefit. During maintenance tx, prophylactic cranial irradiation (PCI) was allowed per protocol; definitive thoracic radiation (TR) was not. Co-primary endpoints were OS and investigator-assessed PFS. Blood tumor mutation burden (bTMB) was an exploratory subgroup analysis using prespecified cutoffs (≥16 vs < 16 and ≥10 vs < 10 mutations/Mb).

Results

Adding atezo to carboplatin + etoposide provided a significant improvement in OS and PFS in 1L ES-SCLC (Table; WCLC 2018:PL02.07). Survival benefits were consistent across key subgroups and prespecified bTMB cutoffs. 44 pts (22 in each arm) received PCI, and 7 pts (3 in atezo arm, 4 in PBO) received TR. Gr 3–4 tx-related adverse events (AE) occurred in 56.6% vs 56.1% of pts in atezo vs PBO arms, respectively; serious tx-related AEs occurred in 22.7% vs 18.9% of pts, respectively. CNS-related AE rates in patients who had PCI are shown in the table.

Atezolizumab + carboplatin + etoposide n = 201PBO + carboplatin + etoposide n = 202
Co-primary endpoints
Median OS, mo12.310.3
HR 0.70 [95% CI 0.54–0.91; P = 0.0069]
Median PFS, mo5.24.3
HR 0.77 [95% CI 0.62–0.96; P = 0.017]
Secondary efficacy endpoints
Investigator-assessed confirmed ORR, %60.264.4
Median DoR, mo4.23.9
CNS-related AEs in pts who had PCI, no. (%)an = 23n = 21
Fatigue12 (52.2)9 (42.9)
Headache8 (34.8)3 (14.3)
Asthenia5 (21.7)2 (9.5)
Dizziness2 (8.7)0
Insomnia2 (8.7)1 (4.8)
Fall2 (8.7)1 (4.8)

Safety population; safety analyses conducted according to tx received (1 pt randomized to the control arm received a dose of atezo).

Conclusions

Adding atezo to carboplatin + etoposide provided a significant improvement in survival in 1L ES-SCLC in all-comers. No unexpected safety signals emerged, including in pts who had PCI or TR. Atezo + carboplatin + etoposide may represent a new standard regimen for pts with untreated ES-SCLC.

Editorial acknowledgement

Support for third-party writing assistance for this manuscript, furnished by Rachel Johnson, Ph.D, of Health Interactions, was provided by Genentech, Inc.

Clinical trial identification

NCT02763579.

Legal entity responsible for the study

F. Hoffmann-La Roche/Genentech, Inc., a member of the Roche Group.

Funding

F. Hoffmann-La Roche/Genentech, Inc., a member of the Roche Group.

Disclosure

T.S.K. Mok: Grants: AZ, Roche/Genentech, BMS, BI, Novartis, MSD, Pfizer, Clovis Oncology, SFJ Pharmaceuticals, Taiho, Eisai, Takeda, Xcovery; Personal fees: AZ, Roche/Genentech, Eli Lilly, BMS, BI, Novartis, MSD, Pfizer, Merck Serono, Clovis Oncology, Vertex, SFJ Pharmaceuticals, ACEA Biosciences, Oncogenex, Celgene, Ignyta Inc, Taiho, Fishawack Facilitate Ltd, Takeda, Janssen, Hutchison ChiMed, OrigiMed, Hengrui Therapeutics, Sanofi-Aventis R&D, Yuhan Corporation; Stock: Hutchison ChiMed and Sanomics; Non-financial support: geneDecode. M. Reck: Personal fees: Roche, Lilly, AZ, Abbvie, BI, BMS, Celgene, MSD, Merck, Novartis, Pfizer. L. Horn: Consultancy: AbbVie, AstraZeneca, Merck, Incyte, Xcovery, Genentech, EMD Serono. S. Lam: Employment: Genentech/Roche. D.S. Shames: Employment: Roche/Genentech; Stock: Roche; Patent pending: Genentech Inc. J. Liu: Employment: Roche (China) Holding Ltd. F. Kabbinavar: Employment: Genentech; Stock: Genentech. W. Lin, A. Sandler: Employment: Roche/Genentech; Stock: Roche. S.V. Liu: Grants: AZ, Bayer, Clovis, Corvus, Genentech, Lilly, Merck, Molecular Partners, Esanex, Pfizer, OncoMed, Blueprint, Lycera, Threshold; Personal fees: AZ, BMS, Celgene, Genentech, Lilly, Pfizer, Taiho, Takeda, Regeneron, Heron.

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