Association between pathologic response and survival after neoadjuvant therapy in lung cancer

Julie Stein Deutsch; Ashley Cimino-Mathews; Elizabeth Thompson; Mariano Provencio; Patrick M. Forde; Jonathan Spicer; Nicolas Girard; Daphne Wang; Robert A. Anders; Edward Gabrielson; Peter Illei; Jaroslaw Jedrych; Ludmila Danilova; Joel Sunshine; Keith M. Kerr; Mia Tran; Judith Bushong; Junliang Cai; Vipul Devas; Jaclyn Neely; David Balli; Tricia R. Cottrell; Alex S. Baras; Janis M. Taube

doi:10.1038/s41591-023-02660-6

Table 1

Baseline characteristics: all path-evaluable patients and patients with or without pathologic evidence of LN involvement

	Path-evaluable population^a
	All		With LN involvement^b		Without LN involvement^b
	Nivolumab plus chemotherapy (n = 141)	Chemotherapy (n = 126)	Nivolumab plus chemotherapy (n = 68)	Chemotherapy (n = 74)	Nivolumab plus chemotherapy (n = 72)	Chemotherapy (n = 51)
Age, median (range), years	64 (46–82)	65 (34–83)	64 (47–76)	65 (34–84)	67 (49–80)	65 (46–82)
Male	69	71	72	72	65	69
Region^c
North America	26	29	26	27	25	33
Europe	20	10	15	12	25	6
Asia	49	55	50	54	47	57
ECOG PS
0	75	68	75	73	75	59
1	25	32	25	27	25	41
Stage^d,e
IB–II	37	39	26	32	46	47
IIIA	63	61	74	68	54	53
Histology
Squamous	47	52	46	51	47	51
Nonsquamous	53	48	54	49	53	49
Smoking status^f
Current/former	89	87	88	85	90	92
Never	11	12	12	15	10	6
Tumor PD-L1 expression^g
Not evaluable	8	8	10	12	6	2
<1%	44	46	48	34	40	63
≥1%	48	46	41	54	54	35
1–49%	29	29	16	35	42	20
≥50%	19	18	25	19	12	16
TMB^h
Not evaluable/not reportedⁱ	50	48	56	51	46	43
<12.3 mut/Mb	29	29	28	30	29	28
≥12.3 mut/Mb	21	23	16	19	25	29

Data reported as % unless otherwise noted.

ECOG PS, Eastern Cooperative Oncology Group performance status.

^aPath-evaluable: patients who underwent surgery and had pathologically evaluable samples.

^bAmong 179 patients randomized to both the nivolumab plus chemotherapy and chemotherapy groups, 149 and 135 received treatment and had definitive surgery, respectively, and 140 and 125 had path-evaluable samples from both PT and LN; LN involvement refers to pathologic evidence of LN disease at resection that had or had not fully regressed after neoadjuvant treatment (0% or >0% RVT in the resected LN).

^cRest of the world: 6% of patients in the nivolumab plus chemotherapy and chemotherapy arms (path-evaluable patient population), 9% and 7% of patients in the nivolumab plus chemotherapy and chemotherapy arms (with LN involvement), 3% and 4% of patients in the nivolumab plus chemotherapy and chemotherapy arms (without LN involvement).

^dDisease stage by case report form, per American Joint Committee on Cancer 7th edition.

^eStage IB, IIA, IIB disease: 6%, 16% and 15% of patients in the nivolumab plus chemotherapy arm and 3%, 21% and 14% in the chemotherapy arm, respectively (path-evaluable patient population); 3%, 16% and 7% of patients in the nivolumab plus chemotherapy arm and 3%, 24% and 5% in the chemotherapy arm, respectively (with LN involvement); 8%, 17% and 21% of patients in the nivolumab plus chemotherapy arm and 4%, 18% and 26% in the chemotherapy arm, respectively (without LN involvement).

^fSmoking status unknown: one patient in the chemotherapy arm (path-evaluable patient population); one patient in the chemotherapy arm (without LN involvement).

^gLevel of PD-L1 expression was determined using the PD-L1 IHC 28-8 pharmDx assay (Dako); patients with tumor tissue that could not be assessed for PD-L1 (≤10% of concurrently randomized patients) were stratified to the PD-L1 expression <1% subgroup at randomization.

^hTMB was evaluated using the Illumina TSO500 assay. A 12.3-mut/Mb cutoff per TSO500 corresponds to 10 mut/Mb per the FoundationOne assay.

ⁱTMB was not analyzed for patients in China; these patients are included in the ‘not reported’ category.