Table 4.
Incidence of treatment-emergent adverse events and duration of exposure by age group
| Adverse event | RAM + ERL | PBO + ERL | ||
|---|---|---|---|---|
| Age < 70 years (n = 157) |
Age ≥ 70 years (n = 64) |
Age < 70 years (n = 166) |
Age ≥ 70 years (n = 59) |
|
| AE | 157 (100) | 64 (100) | 166 (100) | 59 (100) |
| Proteinuriaa | 48 (30.6) | 27 (42.2) | 12 (7.2) | 7 (11.9) |
| Edema peripherala | 30 (19.1) | 20 (31.3) | 4 (2.4) | 6 (10.2) |
| Grade ≥ 3 AE | 107 (68.2) | 52 (81.3) | 88 (53.0) | 33 (55.9) |
| Hypertensionb | 33 (21.0) | 19 (29.7) | 6 (3.6) | 6 (10.2) |
| Diarrheab | 7 (4.5) | 9 (14.1) | 2 (1.2) | 1 (1.7) |
| ALT increasedb | 11 (7.0) | 8 (12.5) | 12 (7.2) | 5 (8.5) |
| SAE | 39 (24.8) | 26 (40.6) | 31 (18.7) | 16 (27.1) |
| Diarrheac | 0 | 3 (4.7) | 0 | 1 (1.7) |
| Pneumothoraxc | 1 (0.6) | 3 (4.7) | 3 (1.8) | 0 |
| ALT increasedc | 0 | 2 (3.1) | 1 (0.6) | 0 |
| Cellulitisc | 2 (1.3) | 2 (3.1) | 0 | 0 |
| Decreased appetitec | 1 (0.6) | 2 (3.1) | 0 | 0 |
| Pneumoniac | 5 (3.2) | 2 (3.1) | 1 (0.6) | 0 |
| Pulmonary embolismc | 0 | 2 (3.1) | 1 (0.6) | 1 (1.7) |
| Discontinued all study treatment due to AE | 18 (11.5) | 10 (15.6) | 17 (10.2) | 7 (11.9) |
| ALT increasedd | 1 (0.6) | 2 (3.1) | 4 (2.4) | 0 |
| Discontinued RAM/PBO alone due to AE | 102 (65.0) | 44 (68.8) | 46 (27.7) | 22 (37.3) |
| Proteinuriad | 30 (19.1) | 8 (12.5) | 0 | 0 |
| Platelet count decreasedd | 8 (5.1) | 6 (9.4) | 2 (1.2) | 0 |
| Neutropeniad,e | 6 (3.8) | 6 (9.4) | 2 (1.2) | 2 (3.4) |
| ALT increasedd | 2 (1.3) | 4 (6.3) | 2 (1.2) | 0 |
| Cardiac failured | 2 (1.3) | 3 (4.7) | 0 | 0 |
| Blood bilirubin increasedd,f | 24 (15.3) | 2 (3.1) | 24 (14.5) | 3 (5.1) |
| Weight decreasedd | 2 (1.3) | 2 (3.1) | 0 | 0 |
| Hemoptysisd | 0 | 2 (3.1) | 0 | 0 |
| Abdominal pain upperd | 0 | 2 (3.1) | 0 | 0 |
| Epistaxisd | 0 | 2 (3.1) | 0 | 0 |
| General physical health deteriorationd | 0 | 2 (3.1) | 0 | 0 |
| Lymphoedemad | 0 | 2 (3.1) | 0 | 0 |
| Melenad | 0 | 2 (3.1) | 0 | 0 |
| Discontinued ERL alone due to AEg | 1 (0.6) | 2 (3.1) | 2 (1.2) | 0 |
| Death due to AEs on study treatmenth | 5 (3.2) | 1 (1.6) | 0 | 0 |
| Duration of exposure, months | ||||
| RAM/PBO | 12.7 (11.0–14.1) | 7.8 (5.6–15.1) | 10.1 (7.4–11.1) | 10.8 (8.3–15.4) |
| Erlotinib | 15.1 (13.8–19.3) | 14.3 (7.3–19.5) | 11.1 (9.7–12.2) | 12.4 (8.9–19.3) |
Data are presented as n (%) or median (95% confidence interval). Censored analysis excluding patients still on treatment. Data cutoff date was 23 January 2019
AE treatment-emergent adverse event, ALT alanine aminotransferase, ERL erlotinib, PBO placebo, RAM ramucirumab, SAE serious adverse event
aAny-grade AEs occurring with a ≥ 10% higher incidence in the RAM+ERL arm in patients aged ≥ 70 vs. < 70 years
bGrade ≥ 3 AEs occurring with a ≥ 5% higher incidence in the RAM + ERL arm in patients aged ≥ 70 vs. < 70 years
cSAEs occurring in ≥ 2% patients aged ≥ 70 years in the RAM + ERL arm
dAEs occurring in ≥ 2% patients aged ≥ 70 years in the RAM + ERL arm
eNeutropenia includes neutrophil count decreased and neutropenia
fBlood bilirubin increased includes hyperbilirubinemia and blood bilirubin increased
gNo AEs occurred in ≥ 2% patients aged ≥ 70 years in the RAM + ERL arm
hDeaths during treatment and within 30 days of discontinuation