LBA9 - IMpower010: Sites of relapse and subsequent therapy from a phase III study of atezolizumab vs best supportive care after adjuvant chemotherapy in stage IB-IIIA NSCLC

Background

Despite treatment with curative intent, up to 60% of patients (pts) with stage I-III NSCLC still experience disease relapse. IMpower010 is the first randomised Phase 3 study to show significant DFS improvement with adjuvant cancer immunotherapy (CIT; atezolizumab [atezo]; anti–PD-L1) after adjuvant chemotherapy in pts with early-stage resected NSCLC (Wakelee ASCO 2021). We explored the sites of relapse and post-relapse treatment (tx).

Methods

Enrolled pts had completely resected stage IB-IIIA NSCLC and ECOG PS 0-1. 1280 pts received up to four 21-day cycles of cisplatin-based chemotherapy (plus pemetrexed, docetaxel, gemcitabine or vinorelbine). 1005 pts were then randomised 1:1 to atezo 1200 mg Q3W (16 cycles or until disease relapse or unacceptable toxicity) or best supportive care (BSC). The DFS primary endpoint was tested hierarchically in PD-L1 TC ≥1% (SP263) stage II-IIIA pts, then in all randomised stage II-IIIA pts and then in ITT stage IB-IIIA pts. Exploratory analyses of relapse sites and post-relapse tx were conducted.

Results

As previously reported, the DFS significance boundary was crossed in PD-L1 TC ≥1% stage II-IIIA (HR [95% CI] 0.66 [0.50, 0.88]) and all randomised stage II-IIIA (HR 0.79 [0.64, 0.96]) pts. In all randomised stage II-IIIA pts, DFS improvement (HR [95% CI]) was seen with increasing PD-L1 expression: TC <1%, 0.97 (0.72, 1.31); TC 1-49%, 0.87 (0.60, 1.26); TC ≥50%, 0.43 (0.27, 0.68). Among PD-L1 TC ≥1% stage II-IIIA pts, 73 (29%) relapsed in the atezo arm vs 102 (45%) in the BSC arm. Sites of relapse and post-relapse tx are shown in the table; further data will be presented, including in all randomised stage II-IIIA and ITT pts.

Conclusions

At this interim DFS analysis, relapse rate was higher in the BSC vs atezo arm, but there was no clear difference in pattern of relapse between the arms among pts with relapse. Post-relapse CIT use was higher in the BSC arm. Table: LBA9

PD-L1 TC ≥1% stage II-IIIA population

^a Patients with relapse/recurrence only.

Clinical trial identification

NCT02486718.

Editorial acknowledgement

Medical writing assistance for this abstract was provided by Kia C. E. Walcott, PhD, of Health Interactions Inc 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

E. Felip: Financial Interests, Institutional, Research Grant: Grant for Oncology Innovation (GOI); Financial Interests, Institutional, Research Grant: Fundación Merck Salud; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Beigene; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Other, Honoraria: Eli Lilly; Financial Interests, Personal, Advisory Board: F. Hoffmann-La Roche; Financial Interests, Personal, Other, Honoraria: F. Hoffmann-La Roche; Financial Interests, Personal, Advisory Board: Glaxo Smith Kline; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Other: Janssen; Financial Interests, Personal, Advisory Board: Medical Trends; Financial Interests, Personal, Other, Honoraria: Medscape; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Other, Honoraria: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Other, Honoraria: Merck Serono; Financial Interests, Personal, Other, Honoraria: Peervoice; Financial Interests, Personal, Advisory Board: Peptomyc; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Other, Honoraria: Springer; Financial Interests, Personal, Advisory Board: Syneos Health; Financial Interests, Personal, Other, Honoraria: Springer; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Other, Honoraria: Touch Medical; Non-Financial Interests, Personal, Leadership Role, President-Elect (2021-2023) of Spanish Society of Medical Oncology (Not compensated): SEOM (Spanish Society of Medical Oncology); Non-Financial Interests, Personal, Leadership Role, Member of the ESMO Nominating Committee and Compliance Committee (Not compensated): ESMO (European Society of Medical Oncology); Non-Financial Interests, Personal, Leadership Role, Member of the Scientific Committee (Not compensated): ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Personal, Leadership Role, Member of the Board of Directors and the Executive Committee (2017 – September 2021): IASLC (International Association for the Study of Lung Cancer); Financial Interests, Personal, Member of the Board of Directors, Independent member of the Board. (Personal fees received): GRIFOLS. E. Vallieres: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Oncocyte; Financial Interests, Personal, Advisory Role: Olympus. C. Zhou: Financial Interests, Personal, Invited Speaker: Roche China; Financial Interests, Personal, Speaker’s Bureau: Lily China BI Sanofi C-Stone Qilu Hengrui Innovent Biologics LUYE Pharma TopAlliance Bioscience Inc Amoy Diagnoistics. H. Wakelee: Financial Interests, Personal, Advisory Board: AstraZeneca, Janssen, Daiichi Sankyo, Blueprint, Mirati, Helsinn; Financial Interests, Personal, Invited Speaker: Fishawack Facilitate LTD, Medscape, Research to Practice, MJH Holdings, Axis Medical Education, Nexus Oncology; Financial Interests, Personal, Writing Engagements: UpToDate; Financial Interests, Personal, Other: Curio Science; Financial Interests, Institutional, Other, Local PI: ACEA Biosciences, Arrys Therapeutics, AstraZeneca/Medimmune, BMS, Clovis Oncology, Novartis, Seagen, Xcovery; Financial Interests, Institutional, Other, Coordinating PI: Celgene; Financial Interests, Institutional, Other, Steering Committee Member: Genentech/Roche, Merck; Non-Financial Interests, Personal, Officer, President-Elect: International Association for the Study of Lung Cancer (IASLC); Non-Financial Interests, Personal, Leadership Role, Executive Committee: ECOG-ACRIN. H. Sakai: Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical Co; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical Co. H. Saito: Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers, Chugai Pharmaceutical. N. Kislov: Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, Eisai, EMD Serono, Exelixis, MSD, Genentech/Roche, GlaxoSmithKline, Ipsen Novartis, Pfizer, Nektar, Lilly; Financial Interests, Personal, Invited Speaker: Biocad, Ipsen, Roche. M. Reck: Financial Interests, Personal, Other, Honoraria for Lecture and Consultancy: AbbVie, Amgen, AstraZeneca, BMS, Boehringer-Ingelheim, Lilly, Merck, MSD, Novartis, Pfizer, Roche/Genentech, Sanofi; Financial Interests, Personal, Other, Personal Fees: Celgene; Financial Interests, Institutional, Research Grant: Roche/Genentech; Non-Financial Interests, Personal, Other, Non-financial support: Roche/Genentech; Financial Interests, Personal, Other, Honoraria for Consultancy: Mirati. V.A. McNally: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. Q. Zhu: Financial Interests, Personal, Full or part-time Employment: Genentech. B. Ding: Financial Interests, Personal, Full or part-time Employment: Genentech. E. Bennett: Financial Interests, Personal, Full or part-time Employment: Genentech. B. Gitlitz: Financial Interests, Personal, Full or part-time Employment: Genentech. N.K. Altorki: Other, Institutional, Research Grant: NCI, DoD, AZ LLC, Jannsen. All other authors have declared no conflicts of interest.