1O - IMpower010: ctDNA status in patients (pts) with resected NSCLC who received adjuvant chemotherapy (chemo) followed by atezolizumab (atezo) or best supportive care (BSC)

Background

IMpower010 (NCT02486718) showed that adjuvant atezo improved disease-free survival (DFS) vs BSC in pts with PD-L1 tumour cell (TC) ≥1% stage II-IIIA NSCLC. While a ctDNA positive (+) status post-surgery (Post-OP ctDNA) conferred poor prognosis, atezo was beneficial vs BSC irrespective of Post-OP ctDNA status (Zhou ESMO-IO 2021). The current exploratory analysis evaluated (1) association of atezo clinical outcomes by PD-L1 status and Post-OP ctDNA status and (2) association of ctDNA clearance post-chemo and pre-atezo cycle 1 day 1 (Post-chemo ctDNA), as well as post-atezo/BSC treatment (on-treatment), with DFS by arm in atezo and BSC pts.

Methods

Of 1005 randomized pts, 600 were evaluated for Post-OP ctDNA using the Signatera (Natera) RUO test. 118 of 600 pts were Post-OP ctDNA+. Of these, 103 pts were evaluated for ctDNA Post-chemo ctDNA and on-treatment at Wk 6 (C3; n=94), Wk 12 (C5; n=85), Wk 18 or 21 (C7/8; n=73) and Wk 42 or 45 (C15/16; n=46). PD-L1 TC subgroups <1%, ≥1%, 1-49% and ≥50% were determined using the VENTANA SP263 assay.

Results

Regardless of Post-OP ctDNA status, atezo was associated with improved DFS vs BSC in PD-L1+ subgroups (TC ≥1%, 1-49%, ≥50%) but not the PD-L1− subgroup (TC <1%). 62.1% (64/103) of Post-OP ctDNA+ pts were cleared (ctDNA−) at Post-chemo ctDNA, which was linked to improved DFS. Atezo improved DFS vs BSC regardless of ctDNA clearance at Post-chemo ctDNA (Cleared: DFS, 31.3 (atezo) vs 13.3 mo (BSC); HR [95% CI], 0.7 [0.37, 1.34] vs Not cleared: DFS, 4.2 vs 3.9 mo; 0.67 [0.34, 1.32]). Longitudinal assessment of ctDNA+ pts at Post-chemo ctDNA showed that atezo maintained ctDNA levels over time, while an approximate 10× increase was observed with BSC. The median time to convert to ctDNA+ in pts who were ctDNA− at Post-chemo ctDNA was longer with atezo vs BSC (not reached vs 4.67 mo; HR, 0.60 [95% CI: 0.31, 1.17]). Similarly, improved DFS was seen with atezo vs BSC in these pts (31.3 vs 13.3 mo; HR, 0.7 [95% CI: 0.37, 1.34]).

Conclusions

Adjuvant atezo is linked to improved DFS vs BSC in early NSCLC in PD-L1+ subgroups regardless of ctDNA status. Chemo ctDNA clearance is associated with longer DFS and atezo may control ctDNA levels and delay disease recurrence better than BSC.

Clinical trial identification

NCT02486718.

Editorial acknowledgement

Medical writing support for this abstract was provided by Michael Williams, 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. Hoffman-La Roche, Ltd.

Disclosure

E. Felip: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Roche, Janssen, Merck Sharp & Dohme, Merck Serono, Pfizer, PeerVoice, Springer, Touch Medical; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Roche, GlaxoSmithKline, Medical Trends, Peptomyc, Puma Biotechnology, Regeneron, Sanofi, Takeda; Other, Institutional, Research Grant, Research Grant: Oncology Innovation, Merck Healthcare KGAa, Fundacion Merck Salud; Other, Personal, Member of the Board of Directors, Independent Member of the Board: GRIFOLS. M. Srivastava: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Roche. M. Reck: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Lilly, MSD, Novartis, Merck, Roche, Sanofi; Financial Interests, Personal, Advisory Board: Mirati, Pfizer, Sanofi, Amgen, AstraZeneca, Boehringer Ingelheim, BMS, MSD, Roche. H. Wakelee: Financial Interests, Institutional, Research Grant, Research Funding: ACEA Biosciences, Arrys Therapeutics, AstraZeneca/MedImmune, BMS, Celgene, Clovis Oncology, Genentech/Roche, Merck, Novartis, Pharmacyclics, Seagen, Xcovery, Helsinn; Financial Interests, Personal, Advisory Board: AstraZeneca, Janssen, Daiichi Sankyo, Blueprint, Mirati; Non-Financial Interests, Personal, Advisory Board: Merck, Genentech/Roche; Other, Personal, Leadership Role, President: IASLC; Other, Personal, Leadership Role, Executive Committee: ECOG-ACRIN. N.K. Altorki: Financial Interests, Institutional, Research Grant, PI: AstraZeneca, Janssen; Financial Interests, Personal, Other, Steering Committee Member: Roche. E. Vallieres: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Oncocyte; Financial Interests, Personal, Advisory Board: BMS. H. Tanaka: Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical, AstraZeneca, Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, AstraZeneca, MSD, Bristol Myers Squibb, Ono Pharmaceutical. S. McCune: Financial Interests, Institutional, Other, Support from Genentech as a research site for this trial: Genentech. E. Bennett, B.J. Gitlitz, V.A. McNally: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. S. Novello: Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Speaker’s Bureau: AMG, Roche, Takeda, Pfizer, AZ, Thermofisher, Novartis, Sanofi, BeiGene; Financial Interests, Personal, Advisory Role, Advisor: AMG, Roche, Takeda, Pfizer, AZ, Novartis, Sanofi, BeiGene. M. Ballinger: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Roche. W. Zou, B. Nabet, M. Das Thakur: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Roche. C. Zhou: Financial Interests, Personal, Invited Speaker: Roche China, Lily China, Boehringer Ingelheim, Sanofi, C-Stone, Qilu, Hengrui, Innovent Biologics, LUYE Pharma, TopAlliance Bioscience Inc, Amoy Diagnostics. All other authors have declared no conflicts of interest.