TABLE 5.

Pooled multivariable analysis including the interaction term between treatment modality and smoking status

	Objective response rate	Progression‐free survival	Overall survival
Variable (comparator)	OR (95% CI); p–value	HR (95% CI); p–value	HR (95% CI); p‐value
Treatment modality (chemotherapy vs. pembrolizumab)	0.79 (0.61–1.03); p = 0.0799	1.93 (1.67–2.23); p < 0.0001	1.27 (1.07–1.51); p = 0.0055
Smoking status (never vs. current/former)	0.68 (0.41–1.12); p = 0.1236	1.71 (1.32–2.25); p < 0.0001	1.51 (1.12–2.04); p = 0.0060
Interaction smoking status*treatment modality	p = 0.0074	p = 0.0001	p = 0.0020
ECOG PS (≥ 2 vs. 0–1)	0.46 (0.31–0.67); p = 0.0001	2.39 (2.01–2.85); p < 0.0001	2.88 (2.37–3.49); p < 0.0001
Gender (male vs. female)	0.98 (0.75–1.26); p = 0.8317	1.04 (0.90–1.21); p = 0.5111	1.12 (0.94–1.33); p = 0.1966
Age (elderly vs. nonelderly)	0.83 (0.66–1.06); p = 0.1295	1.08 (0.94–1.23) p = 0.2531	1.15 (0.99–1.35); p = 0.0650
CNS metastases (yes vs. no)	0.99 (0.72–1.35); p = 0.9193	1.17 (0.99–1.39); p = 0.0611	1.19 (0.97–1.45); p = 0.0861
Liver metastases (yes vs. no)	0.64 (0.45–0.91); p = 0.0124	1.63 (1.37–1.93); p < 0.0001	1.51 (1.24–1.85); p < 0.0001
Bone metastases (yes vs. no)	0.51 (0.38–0.66); p < 0.0001	1.53 (1.33–1.77); p < 0.0001	1.57 (1.33–1.85); p < 0.0001
BMI
Normal weight (comparator)
Underweight	0.53 (0.27–1.01); p = 0.0520	1.26 (0.91–1.74); p = 0.1619	0.97 (0.65–1.44); p = 0.9062
Overweight	0.78 (0.59–1.02); p = 0.0612	0.98 (0.85–1.14); p = 0.8728	0.91 (0.76–1.08); p = 0.3176
Obese	1.41 (0.98–2.04); p = 0.0665	0.81 (0.66–1.01); p = 0.0620	0.89 (0.69–1.14); p = 0.3776
Histology
Nonsquamous vs. squamous	1.07 (0.81–1.42); p = 0.6202	0.85 (0.73–0.99); p = 0.0483	0.94 (0.78–1.14); p = 0.5765

Abbreviations: CNS, central nervous system; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio.