Table 4.
First-Line and Maintenance AEs
| Reference | Study | Intervention | No. of Patients Analyzed (%) | Anemia No. (%) | Hypertension No. (%) | Neutropenia No. (%) | Febrile Neutropenia No. (%) | Leucopenia No. (%) | Thrombocytopenia No. (%) | Diarrhea No. (%) | Nausea No. (%) | Vomiting No. (%) | Fatigue No. (%) | Rash No. (%) | Neuropathy No. (%) | Grade 3 to 4 Overall AEs No. (%) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Rosell et al29 | Eurtac | Erlotinib | 84 (51) | 1 (1.0) | — | 0 (0.0) | 0 (0.0) | — | 0 (0.0) | 4 (5.0) | — | — | 5 (6.0) | 11 (13.0) | 1 (1.0) | 82 (98.0) |
| Standard chemotherapy | 82 (49) | 3 (4.0) | — | 18 (22.0) | 3 (4.0) | — | 12 (14.0) | 0 (0.0) | — | — | 16 (20.0) | 0 (0.0) | 1 (1.0) | 81 (99.0) | ||
| P | .3644 | < .001 | .1183 | < .001 | .0086 | < .001 | 1.0 | |||||||||
| Quoix et al53 | Four cycles carboplatin and paclitaxel | 225 | 21 (9.4) | — | 28 (12.5) | 6 (2.6) | — | 2 (0.9) | 6 (2.7) | 6a | — | — | — | 1 (0.4) | — | |
| Five cycles vinorelbine or gemcitabine | 223 | 10 (4.4) | — | 108 (48.4) | 21 (9.4) | — | 15 (6.7) | 2 (2.9) | 2 (0.9) | — | — | — | 7 (3.1) | — | ||
| Maemondo et al20 | Maemondo (see EGFR PCO59) | Gefitinib | 114 | 0 (0.0) | — | 1 (0.9) | 0 (0.0)b | 0 (0.0) | 0 (0.0) | 1 (0.9) | — | 1 (0.9) | 3 (2.6) | 6 (5.3) | 0 (0.0) | NR (41.2) |
| Carboplatin and paclitaxel | 113 | 6 (5.3) | — | 74 (65.5) | 1 (0.9) | 31 (27.4) | 4 (3.5) | 0 (0.0) | — | 1 (0.9) | 1 (0.9) | 3 (2.7) | 7 (6.2) | NR (71.7) | ||
| P | < .001 | < .001 | < .001 | < .001 | .002 | < .001 | < .001 | < .001 | ||||||||
| Georgoulias et al52 | Docetaxel plus gemcitabine | 155 | 39 (24.8)c | — | 62 (40.0) | 3 (1.9) | — | 8 (5.0) | — | — | — | — | — | 96 (5.7)c | — | |
| Patel et al37 | PointBreak | Pemetrexed, carboplatin, and bevacizumab followed by pemetrexed plus bevacizumab | 442 | 64 (14.5) | 6 (2.1) | 114 (25.8) | 6 (1.4) | — | 103 (23.3) | — | — | — | 48 (10.9) | — | 0 (0.0) | NR |
| Paclitaxel, carboplatin, and bevacizumab followed by bevacizumab | 443 | 12 (2.7) | 0 (0.0) | 180 (40.6) | 18 (4.1) | — | 25 (5.6) | — | — | — | 22 (5.0) | — | 18 (4.1) | NR | ||
| P | < .001 | .01 | < .001 | .02 | — | < .001 | < .001 | < .001 | ||||||||
| Barlesi et al33 | AVAPERL | Maintenance bevacizumab 7.5 mg/kg | 120 | 0 (0.0) | 3 (2.5) | 0 (0.0) | 0 (0.0) | — | 1 (1.8) | — | — | — | 2 (1.7) | — | — | 26 (21.7) |
| Bevacizumab 7.5 mg/kg plus pemetrexed 500 mg/m2 | 125 | 4 (3.2) | 6 (4.8) | 7 (5.6) | 1 (0.8) | — | 0 (0.0) | — | — | — | 3 (2.4) | — | — | 47 (37.6) | ||
| Paz-Ares et al7 | PARAMOUNT | Pemetrexed and cisplatin induction plus maintenance pemetrexed | 359 | NR (6.4) | — | NR (5.8) | NR (1.9) | NR (2.2) | NR (1.9) | NR (0.3) | NR (0.6) | NR (0.3) | NR (4.7) | 0 (0.0) | NR (0.3) | NR |
| Pemetrexed and cisplatin induction plus placebo | 180 | NR (0.6) | — | 0 (0.0) | 0 (0.0) | 0 | 0 | 0 | 0 | 0 | NR (1.1) | 0 | NR (0.6) | NR | ||
| P | ≤ .05 | ≤ .05 | ≤ .05 | |||||||||||||
| Zukin et al55 | Carboplatin and pemetrexed | 103 | 12 (11.7) | — | 7 (6.8) | 1 (1.0) | — | 1 (1.0) | 1 (1.0) | 5 (4.9) | — | — | — | NR | 619 | |
| Zhou et al13 Chen et al14 |
OPTIMALd | Erlotinib | 83 | 0 (0.0) | — | 0 (0.0) | — | — | 0 (0.0) | 1 (1.0) | 0 (or vomiting; 0.0) | — | 0 (0.0) | 2 (2.0) | — | 14 (17.0) |
| Four cycles gemcitabine plus carboplatin | 72 | 9 (13.0) | — | 30 (42.0) | — | — | 29 (40.0) | 0 (0.0) | 1 (1.0) | — | 1 (1.0) | 0 (0.0) | — | 47 (65.0) | ||
| Sequist et al11 | Lux | Afatinib | 229 | 1 (0.4) | — | 1 (0.4) | — | 1 (0.4) | — | 33 (14.4) | 2 (0.9) | 7 (3.1) | 3 (1.3) | 37 (16.2) | — | 112 (49.0) |
| Cisplatin and pemetrexed | 111 | 7 (6.3) | — | 20 (18.0) | — | 9 (8.1) | — | 0 (0.0) | 4 (3.6) | 3 (2.7) | 14 (12.6) | 0 (0.0) | — | 53 (48.0) | ||
| Mok et al6 Solomon et al54e |
PROFILE 1014 | Crizotinib | 171 | 0 (0.0) | — | 19 (11.0) | 0 | 3 (2.0) | 0 (0.0) | 4 (2.0) | 2 (1.0) | 3 (2.0) | 5 (3.0) | — | 2 (1.0) | |
| Pemetrexed plus cisplatin or pemetrexed plus carboplatin | 169 | 15 (9.0) | — | 26 (15.0) | 2 | 9 (5.0) | 11 (7.0) | 1 (1.0) | 3 (2.0) | 5 (3.0) | 4 (2.0) | — | 0 (0.0) |
Abbreviations: AE, adverse event; NR, not reported; PCO, provisional clinical opinion.
a
Nausea and vomiting.
b
Leukocytopenia.
c
Grade 2 to 4.
d
AEs reported in ≥ 3% of participants in either arm.
e
AEs resulting from any cause in as-treated population in ≥ 15% of patients.