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.
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.
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]).
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.
NCT02486718
Medical writing support for this abstract was provided by Michael Williams, PhD, of Health Interactions, Inc. and funded by F. Hoffmann-La Roche, Ltd.