Table 2.

Uni‐ and multivariate analyses of clinicopathological factors and ctDNA load.

	N	PFS							OS
			Univariate analysis			Multivariate analysis				Univariate analysis			Multivariate analysis
		Events	HR	95% CI	P‐value	HR	95% CI	P‐value	Events	HR	95% CI	P‐value	HR	95% CI	P‐value
Age (in years)
≤ 55	34	31	1.00			1.00			16	1.00			1.00
56–70	91	84	0.94	0.62–1.42	0.775	0.91	0.60–1.39	0.671	43	0.65	0.36–1.17	0.146	0.99	0.53–1.87	0.996
> 70	39	36	1.64	1.01–2.68	0.047	1.65	0.99–2.76	0.056	25	0.82	0.43–1.57	0.549	1.47	0.73–2.98	0.280
DFI (in months)
≤ 12	44	40	1.00			1.00			24	1.00			1.00
> 12	120	111	0.98	0.68–1.41	0.903	0.62	0.40–0.97	0.038	60	0.10	0.06–0.18	< 0.001	0.06	0.03–0.12	< 0.001
Visceral metastasis
No	48	41	1.00			1.00			21	1.00			1.00
Yes	116	110	1.45	1.01–2.08	0.043	1.49	1.02–2.17	0.040	63	0.91	0.55–1.50	0.717	1.38	0.81–2.36	0.234
(Neo)Adjuvant therapy
No	72	63	1.00			1.00			40	1.00			1.00
Yes	92	88	1.31	0.95–1.82	0.102	1.70	1.14–2.54	0.010	44	0.78	0.50–1.19	0.246	1.59	0.95–2.64	0.076
Number of lines of therapy for metastatic disease
≤ 2	111	101	1.00			1.00			50	1.00			1.00
> 2	53	50	1.31	0.93–1.84	0.126	1.42	0.99–2.04	0.057	34	1.13	0.73–1.76	0.576	0.77	0.48–1.25	0.296
PR status primary
Negative/unknowna	40	37	1.00			1.00			19	1.00			1.00
Positive	124	114	0.84	0.57–1.21	0.344	0.85	0.58–1.24	0.402	65	1.14	0.68–1.92	0.621	1.45	0.84–2.48	0.182
ECOG screening visit status
ECOG = 0	64	59	1.00			1.00			28	1.00			1.00
ECOGb = 1 or 2	100	92	1.25	0.90–1.75	0.178	1.10	0.77–1.55	0.607	56	1.19	0.75–1.87	0.459	1.52	0.94–2.46	0.085
Number of mutant ctDNA molecules per mL plasma
≤ 54 molecules (no/low ctDNA load)	102	91	1.00			1.00			41	1.00			1.00
> 54 molecules (high ctDNA load)	62	60	1.66	1.19–2.31	0.003	1.64	1.16–2.33	0.006	43	2.20	1.42–3.39	< 0.001	1.83	1.17–2.87	0.008
Number of hotspot mutations
< 3 mutations	135	123	1.00			1.00			64	1.00
≥ 3 mutations	29	28	1.86	1.22–2.83	0.004	2.20	1.43–3.38	< 0.001	20	1.50	0.91–2.49	0.112	1.62	0.97–2.70	0.067
Combined ctDNA load and number of hotspot mutations
Both low	91	80	1.00			1.00			34	1.00			1.00
High/low or low/high	55	54	1.53	1.08–2.18	0.017	1.58	1.10–2.29	0.014	37	2.54	1.58–4.09	< 0.001	2.37	1.44–3.91	0.001
Both high	18	17	2.79	1.63–4.78	< 0.001	2.78	1.61–4.79	< 0.001	13	2.10	1.10–3.99	0.024	1.82	0.95–3.52	0.069

^aPR status is unknown for 11 patients.

^b92 patients with ECOG = 1, 8 patients with ECOG = 2.