Table 2.
Overall safety
| Study | Exposure and follow-up | N | Tx-emergent AEsa |
Tx-related AEsa |
SAEs |
AEs resulting in tx modification or interruption | AEs resulting in tx discontinuation | AEs resulting in death | |||
|---|---|---|---|---|---|---|---|---|---|---|---|
| All grades | Grade ≥3 | All grades | Grade ≥3 | Any | Tx related | ||||||
| Shitara Int J Clin Oncol 2020 (JACOB subgroup analysis)30 |
Median number of cycles (range) per pt: 8 (1-51) for trast 6 (1-51) for cape 6 (1-51) for cis Median follow-up: 34.0 mo |
40 | NR | 75.0% | NR | NR | 32.5% | NR | NR | 10.0% | 2.5% (1 multiple organ dysfunction syndrome) |
| Liu Cancer Commun 2019 (JACOB subgroup analysis)31 |
Average number of cycles ± SD per pt: 11.81 ± 8.35 (placebo + trast) NR for CTX Median follow-up: 18.0 mo |
80 | 97.5% | 65.0% | NR | NR | 15.0% | NR | NR | 6.3% | 7.5% (1 anemia, 1 septic shock, 1 respiratory failure, and 3 deaths) |
| Tabernero Lancet Oncol 2018 (JACOB)32 |
Mean number of cycles ± SD per pt: 11.2 ± 10.0 for trast 5.1 ± 2.7 for cis 7.4 ± 7.6 for cape 5.2 ± 3.5 for 5-FU Median follow-up: 25.0 mo |
388 | 99% | 73% | NR | NR | 39% (5% diarrhea) | 10% | 54% for cape 28% for 5-FU 19% for cis |
12% (disc of placebo and trast) | 8% (2% tx related: 1 multiple organ failure, 1 pulmonary embolism, 1 hemodynamic instability, 1 unexplained death, and 3 septic shock) |
| Shah J Clin Oncol 2017 (HELOISE)28 |
Median number of cycles (range) per pt: 6.5 (1-36) for trast 6 (1-7) for cape 6 (1-7) for cis |
124 | 91.1% | 59.7% | 88.7% (38.7% related to trast) | NR | 24.2% (all grade ≥3) | 18.5% | NR | 7.3% (any tx disc) 2.4% (trast disc) |
5.6% |
| Sawaki Gastric Cancer 2012 (ToGA subgroup analysis)29 |
Median number of cycles (range) per pt: 8 (1-24) for trast NR for cape NR for cis Median follow-up: 18.6 mo |
51 | 100% | 84% | 2% | NR | NR | NR | NR | 2% | 3.9% (1 cardiac failure & unstable angina likely related to trast, and 1 gastrointestinal perforation) |
| Bang Lancet 2010 (ToGA)6 |
Median number of cycles (range) per pt: 8 (1-49) for trast 6 (1-14) for cis 6 (1-20) for cape 6 (1-6) for 5-FU Median follow-up: 18.6 mo |
294 | 99% | 68% | NR | NR | 32% | NR | 84% | NR | 3% (tx related) |
| Yuki Cancer Chemother Pharmacol 2020 (KSCC/HGCSG/CCOG/Perseus 1501B)27 |
Median number of cycles (range) per pt: 8 (1-33) Median follow-up: 22.4 mo |
39 | NR | NR | NR | NR | NR | NR | NR | 16% | 0% (tx related) |
| Rivera Cancer Chemother Pharmacol 2019 (HERXO)33 |
Median follow-up: 13.7 mo | 45 | 93% | 44% | NR | NR | NR | NR | Tx modif: 38% for oxal 36% for cape 18% for trast |
NR | NR |
| Takahari Gastric Cancer 2019 (HIGHSOX)34 |
Median number of cycles (range) per pt: 8 (1-36+) Median follow-up: 15.6 mo |
75 | NR | NR | 98.6% | 45.3% | NR | NR | Tx modif: 54.6% for S-1 50.6% for oxal 10.6% for trast Tx interr: 50.6% for S-1 46.6% for oxal 40.0% for trast |
18.6% (disc of S-1) 29.3% (disc of oxal) 0% (disc of trast) |
0% (tx related) |
| Miura Gastric Cancer 2018 (WJOG7212G/T-SPACE)35 |
Median number of cycles (range) per pt: 5.0 (1.0-17.0) for S-1 5.0 (0-8.0) for cis 8.5 (1.0-29.0) for trast Median follow-up: 19.3 mo |
44 | NR | NR | NR | NR | NR | NR | NR | 15.9% | 2% (tx related) |
| Ryu Eur J Cancer 201526 |
Median number of cycles (range) per pt: 10 (1-30) for cape 8 (1-30) for oxal 10 (1-30) for trast Median follow-up: 13.8 mo |
55 | NR | NR | NR | NR | NR | NR | NR | 2% | 2% (tx-related diarrhea and sepsis) |
| Kurokawa Br J Cancer 2014 (HERBIS-1)23 |
Median number of cycles (range) per pt: 6 (1-27) Median follow-up: 13.5 mo |
53 | NR | NR | NR | NR | NR | NR | NR | 30% | 2% (tx-related myelosuppression) |
| Gong BMC Cancer 2016 (CGOG1001)36 |
Median number of cycles (range) per pt: 8 (1-32) Median follow-up: 28.6 mo |
51 | NR | NR | NR | NR | 16% | NR | Tx modif: 24% for oxal 33% for cape Tx interr: 4% for trast |
4% | 2% (septic shock) |
| Oh Cancer Chemother Pharmacol 201925 |
Median number of cycles (range) per pt: 6 (1-17) for trast + CTX 3 (0-61) for trast single-agent maintenance |
123 | NR | NR | NR | NR | NR | NR | NR | 0% | NR |
| Okita Tohoku J Exp Med 201837 |
Mean delivered dose intensity (cis): 14.8 mg/m2/week Relative dose intensity (cis): 55.6% |
28 | 92.9% | 60.7% | NR | NR | NR | NR | NR | NR | NR |
| Okita Tohoku J Exp Med 201837 |
Mean delivered dose intensity (cis): 10.5 mg/m2/week Relative dose intensity (cis): 52.6% |
30 | 93.3% | 56.7% | NR | NR | NR | NR | NR | NR | NR |
| Soularue Bull Cancer 201519 |
Median number of cycles (range) per pt: 13 (3-38) for trast 8 (2-12) for oxal Median follow-up: 14.7 mo |
34 | NR | 32% | NR | NR | NR | NR | NR | NR | 0% (tx related) |
| Kim BMC Cancer 202120 |
Median number of cycles (range) per pt: 8 (1-56) for trast 6 (1-15) for cis 7 (1-56) for cape 6 (1-8) for 5-FU Median follow-up: 18.8 mo |
47 | NR | NR | NR | NR | NR | NR | NR | 17% (disc of cis) | 8.5% (tx-related pneumonia and sepsis, heart failure, cerebral infarction) |
| Dijksterhuis Int J Cancer 202022 |
NR | 71 | 45.1% | 40.8% | NR | NR | NR | NR | NR | NR | 4% |
| Li Clin Transl Oncol 201821 |
Median number of cycles (range) per pt: 9 (1-44) Median follow-up: 14.0 mo |
107 | NR | NR | NR | NR | NR | NR | NR | 1% (disc of trast for ↓ LVEF) | 0% (tx related) |
| Janjigian Lancet Oncol 202015 |
Median number of cycles (IQR) per pt: 6 (5-8) for oxal 10 (7-17) for pembro/trast/ fluoropyrimidine combined Median follow-up: 13 mo |
37 | NR | NR | 97% | 57% | 5% | 5% | 97% (tx modif) | 5% (tx related) | 0% (tx related) |
| Lee AACR 2021, Abstr. CT174 (HCRN GI17-319)24 |
NR | 18 | NR | NR | NR | NR | NR | NR | NR | NR | NR |
| Rha ASCO 2020, Abstr. 3031 Rha ASCO GI 2021, Abstr. 218 (PANTHERA)17 |
Median follow-up: 18.2 mo | 43 | NR | NR | 98% | 81% | NR | NR | NR | NR | NR |
| Janjigian ASCO 2021, Abstr. 4013 (KEYNOTE-811)14 |
Median follow-up for safety: 9.9 mo Median follow-up for efficacy: 12.0 mo |
216 (placebo) 217 (pembro) |
98% 97% |
57% 57% |
NR NR |
NR NR |
38% 31% |
NR NR |
NR NR |
26% 24% |
5% 3% |
5-FU, 5-fluorouracil; AE, adverse event; cape, capecitabine; cis, cisplatin; CTX, chemotherapy; disc, discontinuation; IQR, interquartile range; LVEF, left ventricular ejection fraction; modif, modification of dosage; NR, not reported; oxal, oxaliplatin; pembro, pembrolizumab; pt, patient; SAE, serious adverse event; SD, standard deviation; ToGA, Trastuzumab for Gastric Cancer; trast, trastuzumab; tx, treatment.
a
While treatment emergent AEs refers to adverse events that occur only once treatment has started, regardless of causality, treatment-related AEs refer to adverse events that are considered by the investigator as related to treatment.