Table 4.

Relative risk of developing pneumonitis reported in NSCLC while on treatment^a by LOT

Assessment	LOT 1 (N = 17,679)		LOT 2 (N = 7,158)		LOT 3 (N = 3,062)
	RR (95% CI)	P value	RR (95% CI)	P value	RR (95% CI)	P value
Demographic characteristics
Age ≥ 65 (yes vs. no)	1.023 (0.935, 1.119)	0.6177	1.174 (1.032, 1.336)	0.0150*	0.882 (0.729, 1.067)	0.1975
Gender—male (yes vs. no)	1.254 (1.148, 1.370)	<0 .0001*	1.441 (1.269, 1.637)	<0 .0001*	1.178 (0.975, 1.424)	0.0902
Race (African American vs. Caucasian)	0.932 (0.799, 1.088)	0.3736	0.887 (0.715, 1.100)	0.2733	1.030 (0.756, 1.404)	0.8513
Race (Asian vs. Caucasian)	0.983 (0.700, 1.381)	0.9219	0.772 (0.477, 1.248)	0.2904	0.657 (0.339, 1.273)	0.2136
Histology
Squamous vs. non-squamous [[2]]	1.443 (1.314, 1.585)	<0 .0001*	1.843 (1.607, 2.114)	<0 .0001*	1.623 (1.301, 2.025)	<0 .0001*
Biomarker status
EGFRc (positive vs. negative)	0.853 (0.736, 0.988)	0.0339*	0.793 (0.653, 0.963)	0.0195*	0.836 (0.645, 1.083)	0.1745
PD-L1 (positive vs. negative)	1.302 (0.922, 1.839)	0.1335	0.986 (0.644, 1.508)	0.9470	0.754 (0.393, 1.446)	0.3953
History of adverse events
CCI score (1–4 vs. 0)	1.129 (1.031, 1.236)	0.0086*	1.043 (0.917, 1.185)	0.5234	1.077 (0.890, 1.303)	0.4465
History of pneumonitis (yes vs. no)	1.178 (1.067, 1.302)	0.0012*	1.193 (1.035, 1.376)	0.0147*	1.228 (0.989, 1.526)	0.0630
History of diabetes (yes vs. no)	3.632 (3.296, 4.002)	<0 .0001*	3.768 (3.317, 4.281)	< 0.0001*	3.215 (2.659, 3.886)	<0 .0001*
Treatment category
Any ICI monotherapy (yes vs. no)	1.397 (1.210, 1.613)	<0 .0001*	1.856 (1.629, 2.116)	<0 .0001*	1.322 (1.085, 1.610)	0.0056*
Any ICI combination therapy (yes vs. no)	1.495 (1.159, 1.930)	0.0020*	1.395 (0.970, 2.007)	0.0726	1.347 (0.696, 2.608)	0.3762
EGFR TKI therapy (yes vs. no)	0.936 (0.805, 1.087)	0.3841	0.909 (0.729, 1.133)	0.3943	1.671 (1.304, 2.142)	<0 .0001*
Other targeted therapy (yes vs. no)	0.416 (0.338, 0.512)	<0 .0001*	0.337 (0.258, 0.442)	< 0.0001*	0.440 (0.300, 0.646)	< .0001*
Any platinum-based chemotherapy (yes vs. no)	1.128 (1.023, 1.244)	0.0156*	1.141 (0.977, 1.333)	0.0954	1.069 (0.794, 1.439)	0.6614
Any non platinum-based chemotherapy (yes vs. no)	0.753 (0.638, 0.888)	0.0008*	0.648 (0.564, 0.743)	<0 .0001*	0.625 (0.510, 0.764)	<0 .0001*
Radiation therapy
History of radiation therapy (yes vs. no)	1.532 (1.387, 1.692)	<0 .0001*	1.435 (1.216, 1.693)	<0 .0001*	1.837 (1.387, 2.433)	<0 .0001*

All categories within the “assessments” column represent the presence of the condition during the baseline period, which is defined as any time prior to index date or start of LOT. Shaded cells represent parameters that were significant at the 0.05 level

N = Number of patients eligible for analysis

^aEvaluation period is from start of LOT to 30 days after end of current LOT or day prior to start of next LOT, whichever was earlier, or (where there was no next LOT) up to end of follow-up for patient or end of LOT + 30, whichever was earlier

RR: Relative risk of developing pneumonitis derived by calculating IR1/IR2. P values to test the relative risk of developing pneumonitis were derived from a generalized linear model after accounting for differential patient follow-up times

^bPatients with squamous cell carcinoma were compared against patients with non-squamous cell carcinoma only. Non-squamous NSCLC includes adenocarcinoma and large cell lung cancer. Patients with unknown histology were excluded from this analysis

^cA patient was deemed to be EGFR-mutant if identified as EGFR-positive from the SDS data set or had received osimertinib, erlotinib, afatinib, gefitinib or dacomitinib (monotherapy or in combination with chemotherapy drugs) in LOT1

Regimens whose start date were lying on or after January 1, 2008, were considered for the analysis

CCI Charlson Comorbidity Index; EGFR epidermal growth factor receptor; ICI immune checkpoint inhibitor; LOT line of therapy; NSCLC non-small cell lung cancer; PD-L1 programmed death-ligand 1; SDS signs, diseases, and symptoms; TKI tyrosine kinase inhibitor