Table 2.
Clinical and oncologic outcomes of GTN patients treated with avelumab or pembrolizumab for GTN included in this systematic review.
| Immunotherapy | Authors | Age | Histology | Number of cycles to remission | Number of consolidation cycles | Toxicity of (CTCAE grade) | Oncologic Outcome | Relapse after immunotherapy# | Reproductive outcomes |
|---|---|---|---|---|---|---|---|---|---|
| Avelumab | You et al.a | 34b | All GTN cases are post CHM | 8 (median) range 2‒11 | 3 (per protocol) | d | Remission in 8/15 (53.3%) | No cases reported (29 months) | e |
| Pembrolizumab | Ghorani et al. | 39 | CC | 4 | 5 | Arthralgia (G1) | Remission | No relpase after 24 months | Not reported |
| 44 | Mixed PSTTand ETT | 5 | ‒ | Pruritis (G1) | Death | ‒ | TAH | ||
| 47 | PSTT | 8 | 5 | Synovitis (G2) Rash (G1) | Remission | No relpase after 15 months | Not reported | ||
| 37 | CC | 2 | 5 | Neutropaenia (G2) Synovitis (G1) | Remission | No relpase after 5 months | Not reported | ||
| Huang et al. | 26 | CC | 2 | 2 | Hepatotoxicity (G3) | Remission | No relpase after 2 months | Not reported | |
| Choi et al. | 39 | PSTT | 1 | 13 | Not reported | Remission | No relpase after 29 months | TAH | |
| 26 | ETT | 11 | 4** | Rash (G2) | Remission | *** | TAH | ||
| Clair et al. | 30 | CC | 10 | Not reported | Not reported | Remission | No relpase after 31 months | TAH | |
| Goldfarb et al. | 50 | CC | 3 | 3 | Peripheral neuropathy (G3) | Progression1 | Under treatment | TAH | |
| Pisani et al. | 49 | ETT | Not reported | Not reported | Not reported | Remission | No relpase after 12 months | TAH | |
| Bell et al. | 47 | ETT | 29 cycles *** | ‒ | Not reported | Remission | *** | Not reported | |
| Porter et al. | 34 | PSTT | 3 | Not reported2 | Inflammatory thyroiditis (no grade reported) | Remission | *** | TAH | |
| Polnaszek et al. | 23 | PSTT | 3 | ‒ | Not reported | Remission | No relpase after 12 months | 3 | |
| Paspalj et al. | 31 | CC | 4 | 3 | Not reported | Remission | No relpase after 24 months | TAH | |
| Wong et al. | 44 | CC | **** | **** | Arthralgia (G1) | Remission | Relpase after 6 months***** | Not reported |
cComplete hydatidiform mole.
* Need to reduce the dosage of the 2 consolidation cycles of pembrolizumab in 50% due to toxicity.
** The institution's tumor board decided to continue treatment with pembrolizumab, even after remission.
*** The patient was still undergoing consolidation chemotherapy at the time of publication of the case report.
**** The patient achieves remission after 2 cycles of pembrolizumab (followed by 5 consolidation cycles). However, she relapsed after 6 months and was again treated with pembrolizumab. The report was unclear but suggested that the patient achieved remission after 4 further cycles of pembrolizumab, followed by 21 consolidation cycles.
***** After GTN relapse notwithstanding the treatment with pembrolizumab, the patient was rescued with pembrolizumab and achieved remission again, with no evidence of disease and with normal hCG levels after 24 months of the end of immunotherapy.
Between parentheses, the follow-up time, in months, after remission is presented, using the median for the study by You et al.
CTCAE, Common Terminology Criteria for Adverse Events (reference 16); CC, Choriocarcinoma; PSTT, Placental site trophoblastic tumor; ETT, Epithelioid trophoblastic tumor; TAH, Underwent Total Abdominal Hysterectomy before pembrolizumab.
Clinical trial with 15 patients treated with avelumab.
Median.
Two cases hyperthyroidism (13.3%), one case of hypothyroidism (6.7%); and one case of a grade 2 ovarian cyst (6.7%) and another case of a grade 3 uterine bleeding (6.7%), which were both unrelated to treatment.
One case of healthy baby born vaginally at 39 weeks of gestation.
. Relapse after 8 months. She was followed up with hCG monitoring and imaging exams until reinitiating pembrolizumab after 14 months from the relapse.
. Although the number of consolidation chemotherapy cycles with pembrolizumab was not reported, the authors reported that they used, in addition to pembrolizumab, 5 consolidation cycles with the EP/EMA regimen, replacing cisplatin to carboplatin in the last cycle due to toxicity (thrombocytopenia, ototoxicity and tinnitus). Finally, the authors reported that she is still on consolidation treatment with pembrolizumab.
. Since the diagnosis of PSTT, the patient has refused to undergo hysterectomy or even conventional chemotherapy for PSTT, accepting only treatment with pembrolizumab. The patient achieved remission with immunotherapy and became pregnant during consolidation chemotherapy with pembrolizumab, which was immediately discontinued. The pregnancy progressed uneventfully with a delivery of a healthy baby born vaginally at 39 weeks of gestation.