Real-World Safety and Efficacy of Nivolumab in Advanced Squamous and Nonsquamous Non-Small-Cell Lung Cancer: A Retrospective Cohort Study in Croatia, Hungary, and Malta

Table 2

Safety and efficacy of nivolumab.

	All patients (n = 239)	Tumor histology
		Squamous (n = 81)	Nonsquamous (n = 158)
Safety endpoints
Treatment discontinuation because of toxicity	27 (11.6)	12 (15.0)	15 (9.9)
Treatment-related adverse events
Any grade	59 (24.7)	20 (24.7)	39 (24.7)
Grades III-IV	12 (5.0)	4 (4.9)	8 (5.1)
Treatment-related, immune-mediated adverse events
Any grade	44(18.4)	16 (19.8)	28 (17.7)
Grades III-IV	10 (4.2)	4 (4.9)	6 (3.8)
All adverse events
Dermatitis, rash, and pruritus	31 (13.0)	6 (7.4)	25 (15.8)
Hypothyroidism	10 (4.2)	4 (4.9)	6 (3.8)
Fatigue	9 (3.8)		9 (5.7)
Diarrhea	8 (3.3)	4 (4.9)	4 (2.5)
Hepatotoxicity	6 (2.5)	2 (2.5)	4 (2.5)
Pneumonitis	5 (2.1)	3 (3.7)	2 (1.3)
Anemia	5 (2.1)	3 (3.7)	2 (1.3)
Neuropathy	4 (1.7)		4 (2.5)
Fever, infection	3 (1.3)	2 (2.5)	1 (0.6)
Other, each <1%^∗	13 (5.4)	6 (7.4)	7 (4.4)
Efficacy endpoints
Best objective response, n (%)
Complete response (CR)	5 (2.2)	1 (1.2)	4 (2.7)
Partial response (PR)	43 (18.8)	17 (21.0)	26 (17.6)
Stable disease (SD)	105 (45.9)	41 (50.6)	64 (43.2)
Progressive disease (PD)	35 (15.3)	10 (12.3)	25 (16.9)
Could not be determined	41 (17.9)	12 (14.8)	29 (19.6)
Objective response rate, n (%)	48 (21.0)	18 (22.2)	30 (20.3)
Disease control rate, n (%)	153 (66.8)	59 (72.8)	94 (63.5)
TTR (months), median (95% CI)	3.2 (2.4–5.0)	2.2 (2.0–3.2)	5.1 (2.6–7.0)
Unadjusted HR (95% CI)		3.05 (1.53–6.07)	1.00 (referent)
Adjusted HR (95% CI)^†		2.64 (1.28–5.43)	1.00 (referent)
DOR (months), median (95% CI)	19.1 (12.9-†)	31.0 (9.6-‡)	17.2 (12.2-‡)
Unadjusted HR (95% CI)		0.61 (0.26–1.42)	1.00 (referent)
Adjusted HR (95% CI)^†		0.70 (0.24–2.08)	1.00 (referent)
PFS (months), median (95% CI)	6.4(5.2–8.6)	8.2 (6.0–10.4)	5.5 (4.4–8.3)
Unadjusted HR (95% CI)		0.90 (0.67–1.20)	1.00 (referent)
Adjusted HR (95% CI)^†		0.66 (0.47–0.93)	1.00 (referent)
OS (months), median (95% CI)	14.1 (10.6–18.0)	13.9 (10.0–20.0)	15.2 (10.0–20.3)
Unadjusted HR (95% CI)		1.07 (0.78–1.46)	1.00 (referent)
Adjusted HR (95% CI)^†		0.86 (0.61–1.23)	1.00 (referent)

Abbreviations: CI = confidence interval; TTR = time to response; DOR = duration of response, PFS = progression-free survival; OS = overall survival. Other adverse events observed in <1% of patients each were arthritis, migrating arthralgia, myositis, cardiotoxicity, herpes zoster ophthalmicus, colitis, thrombocytopenia, pain, myalgia, encephalopathy, and nausea. ^†Analysis of TTR, DOR and PFS was adjusted for age at the introduction of nivolumab, sex, previous treatment of metastatic disease with tyrosine kinase inhibitors, number of metastatic sites, ECOG performance status at introduction of nivolumab, time from diagnosis to introduction of nivolumab (years), and, as the time-dependent covariate, concomitant radiotherapy; analysis of OS was additionally adjusted for therapy after the discontinuation of nivolumab and the time-dependent covariate number of cycles. ^‡Statistic could not be estimated. Data were missing for 3 patients for time to response and duration of response; 7 patients for treatment discontinuation; and 10 patients for the best response.