Table 2.

Hazard ratios (95% CIs) contrasting occurrence versus no occurrence of irAEs on survival and response rates to ICI using different estimation methods

	OS	PFS	ORR	CR
Original cohort, HR (95% CI)
Naive cox	0.41 (0.26–0.65)	0.37 (0.25–0.56)	2.26 (1.26–4.05)	1.55 (0.68–3.51)
Time-updated cox	1.10 (0.69–1.75)	0.88 (0.59–1.30)	1.27 (0.68–2.36)	0.77 (0.35–1.70)
Emulated cohort, HR (95% CI)
TTE	0.90 (0.62–1.30)	1.02 (0.72–1.44)	1.43 (0.89–2.29)	1.47 (0.78–2.76)

All models were for adjusted for age, and sex, study center, therapy line, ECOG (0/ ≥ 1), and localization of metastases (lymph node only disease/visceral metastases/missing) were added as strata. The TTE pooled weighted Cox model was additionally adjusted for study number as a natural cubic spline.

There were no statistically significant differences regarding sex or therapy line for any endpoint (all p-values for interaction > 0.1 for all four endpoints both for the naive and updated Cox models, and the Cox models from the emulated cohort)

OS, overall survival; PFS, progression-free survival; ORR, objective response rate; CR, complete response