Table 2.
Adverse Events Overall and Per Treatment Group
| Standard Dose a |
Extended Interval Dosing a |
P Value |
||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event |
Total Events |
Escalation Windowb |
Total Events |
Escalation Window |
Total Events |
Escalation Window |
||||
| Any Grade | Grade ≥3 | Any Grade | Grade ≥3 | Any Grade | Grade ≥3 | Any Grade | Grade ≥3 | Any grade/Grade ≥3 | Any grade/Grade ≥3 | |
| Overall | n = 88 | n = 51 | n = 117 | n = 117 | ||||||
| All events, n (% of all) | 118 | 20 (16.9) | 69 | 11 (15.9) | 237 | 21 (8.9) | 110 | 12 (10.9) | .02*/.42 | .003*/.1 |
| Adjuvant durvalumab | n = 17 | n = 15 c | n = 49 | n = 49 | ||||||
| All events, n (% of all) | 26 | 3 (11.5) | 19 | 2 (10.5) | 79 | 6 (7.6) | 46 | 5 (10.9) | .75/.58 | .11/.74 |
| Skin | 8 (30.8) | 1 (33) | 6 (31.6) | - | 24 (30.4) | 1 (17) | 8 (17.4) | - | ||
| Fatigue | 5 (19.2) | - | 3 (15.8) | - | 23 (29.1) | - | 15 (32.6) | - | ||
| Endocrinopathy | 3 (11.5) | - | 2 (10.2) | - | 10 (12.7) | - | 7 (15.2) | - | ||
| Gastrointestinal | 3 (11.5) | 2 (67) | 3 (15.8) | 2 (100) | 7 (8.9) | 2 (33) | 5 (10.9) | 2 (40) | ||
| Musculoskeletal | 3 (11.5) | - | 1 (5.3) | - | 7 (8.9) | - | 5 (10.9) | - | ||
| Pneumonitis | 3 (11.5) | - | 3 (15.8) | - | 4 (5.1) | 3 (50) | 4 (8.7) | 3 (60) | ||
| Hepatitis | - | - | - | 2 (2.5) | - | 1 (2.2) | - | |||
| Sicca syndrome | 1 (3.8) | - | 1 (5.3) | - | - | - | - | - | ||
| Ocular | - | - | - | - | 1 (1.3) | - | - | - | ||
| Nephritis | - | - | - | - | 1 (1.3) | - | 1 (2.2) | - | ||
| Pembrolizumab mono | n = 30 | n = 19 c | n = 35 | n = 35 | ||||||
| All events, n (% of all) | 39 | 10 (25.6) | 23 | 6 (26.1) | 80 | 7 (8.8) | 28 | 5 (17.9) | .02*/.36 | .01*/.14 |
| Skin | 12 (30.8) | 3 (30) | 6 (26.1) | 2 (33.3) | 33 (41.3) | 2 (28.6) | 7 (25) | 1 (20) | ||
| Fatigue | 5 (12.8) | - | 3 (13) | - | 11 (13.8) | - | 4 (14.3) | - | ||
| Endocrinopathy | 9 (23.1) | - | 5 (21.7) | - | 16 (20.0) | 1 (14.3) | 5 (17.9) | 1 (20) | ||
| Gastrointestinal | 4 (10.3) | 4 (40) | 2 (8.7) | 2 (33.3) | 6 (7.5) | 1 (14.3) | 5 (17.9) | 1 (20) | ||
| Musculoskeletal | 3 (7.7) | - | 3 (13) | - | 5 (6.3) | 1 (14.3) | - | - | ||
| Pneumonitis | 3 (7.7) | 2 (20) | 2 (8.7) | 1 (16.7) | 3 (3.7) | 1 (14.3) | 3 (10.7) | 1 (20) | ||
| Hepatitis | 3 (7.7) | 1 (10) | 2 (8.7) | 1 (16.7) | 2 (2.5) | 1 (14.3) | 2 (7.1) | 1 (20) | ||
| Sicca syndrome | - | - | - | - | 2 (2.5) | - | - | - | ||
| Ocular | - | - | - | - | 1 (1.3) | - | 1 (3.6) | - | ||
| Infusion related reaction | - | - | - | - | 1 (1.3) | - | 1 (3.6) | - | ||
| Nivolumab mono | n = 30 | n = 16 c | n = 18 | n = 18 | ||||||
| All events, n (% of all) | 33 | 5 (15.1) | 25 | 3 (12) | 50 | 6 (12) | 18 | 1 (5.6) | .08/.12 | .13/.46 |
| Skin | 5 (15.2) | - | 4 (16) | - | 15 (30) | 1 (16.7) | 3 (16.7) | - | ||
| Fatigue | 6 (18.2) | - | 3 (12) | - | 11 (22) | - | 4 (22.2) | - | ||
| Endocrinopathy | 3 (9.1) | - | 3 (12) | - | 7 (14) | 1 (16.7) | 3 (16.7) | 1 (100) | ||
| Gastrointestinal | 11 (33.3) | 2 (40) | 10 (40) | 2 (66.7) | 10 (20) | 1 (16.7) | 6 (33.3) | - | ||
| Musculoskeletal | 2 (6.1) | 1 (20) | 2 (8) | 1 (33.3) | 2 (4) | - | - | - | ||
| Pneumonitis | 3 (9.1) | 1 (20) | 1 (4) | - | 1 (2) | - | 1 (5.6) | - | ||
| Hepatitis | - | - | - | - | 2 (4) | 1 (16.7) | 1 (5.6) | - | ||
| Sicca syndrome | - | - | - | - | 1 (2) | 1 (16.7) | - | - | ||
| Ocular | 1 (3) | - | 1 (4) | - | - | - | - | - | ||
| Infusion related reaction | 1 (3) | 1 (20) | - | - | 1 (2) | 1 (16.7) | - | - | ||
| Neurological | 1 (3) | - | 1 (4) | - | - | - | - | - | ||
| Pembro + chemo | n = 11 | n = 1 c | n = 15 | n = 15 | ||||||
| All events, n (% of all) | 20 | 2 (10) | 2 | - | 28 | 2 (7.1) | 18 | 1 (5.6) | .87/.84 | N.a./N.a. |
| Skin | 4 (20) | - | - | - | 6 (21.4) | - | 4 (22.2) | - | ||
| Fatigue | 6 (30) | - | 1 (50) | - | 5 (17.9) | - | 4 (22.2) | - | ||
| Endocrinopathy | 2 (10) | - | - | - | 8 (28.6) | - | 4 (22.2) | - | ||
| Gastrointestinal | 3 (15) | - | - | - | 3 (10.7) | - | 2 (11.1) | - | ||
| Musculoskeletal | 1 (5) | - | - | - | 1 (3.6) | - | 1 (5.6) | - | ||
| Pneumonitis | 1 (5) | - | - | - | 1 (3.6) | 1 (50) | - | - | ||
| Hepatitis | 1 (5) | 1 (50) | - | - | 2 (7.1) | 1 (50) | 1 (5.6) | 1 (100) | ||
| Sicca syndrome | 1 (5) | - | 1 (50) | - | 2 (7.1) | - | 2 (11.1) | - | ||
| Cardiovascular | 1 (5) | 1 (50) | - | - | - | - | - | - | ||
a
Adverse events were assessed in the standard dose cohort (SD) and the EI dosing cohort (EI).
b
Start of the escalation window is defined as the moment in which patients were escalated from standard (SD) to the extended dose interval due to the COVID-19 pandemic: 4 weeks after start of treatment with adjuvant durvalumab, or 6 weeks after start of pembrolizumab mono- or consolidation therapy or nivolumab monotherapy.
c
Decreased case number due to drop out of patients before entering the escalation window as result of early ICI-related adverse events and/or early progression of disease.
⁎
P-value ≤ .05 considered statistically significant. N.a., not assessed. N, number of patients