Table 5.
Detailed characteristics of phase III trials.
| Author, year, type of study | Time of study | N (total) | Intrinsic subtypes | TLDM | Treatment | Other therapies (ITT, ET, ChT, RT) | Safety | CNS-specific response | Survival |
|---|---|---|---|---|---|---|---|---|---|
| Boogerd et al. (2004)65 Phase III |
1991–1998 | 35 BC pts with LMD (study closed prematurely because of poor accrual in the IT arm) | – | – | IT arm: systemic therapy plus IF/RT (30 Gy/10 fr) plus IT MTX Non-IT arm: systemic therapy (CAF, FEC and CMF) plus IF/RT (30 Gy/10 fr) |
Yes | Delayed leukoencephalopathy 18% (IT) vs 6% (non-IT) Serious gait disturbance 65% (IT) vs 28% (non-IT) Moderate headache 41% (IT) vs 22% (non-IT) Moderate cognitive impairment 53% (IT) vs 22% (non-IT) Neurological complications 47% (IT) vs 6% (non-IT) (p=0.0072) 1 death in the IT group after Ommaya reservoir insertion and before MTX infusion |
Neurological improvement: 41% (IT) vs 39% (non-IT) Neurological stabilization = 18% vs 28% Mean time to neurological progression in responders = 43 weeks (IT) vs 64 weeks (non-IT) |
mOS 18.3 weeks in the IT arm vs 30.33 weeks in the non-IT arm (p=0.32) mOS of 6 IT patients who achieved cytological response 52 weeks |
| Le Rhun et al. (2020)66 Phase III DEPOSEIN trial |
2011–2018 | 73 pts | In the control arm: 7 pts TNBC (19%), 9 pts HER2+ (24%) – 24 patients ER+ (65%) – 18 PR+ (29%) In the experimental arm: 5 TNBC (14%) – 2 HER2+ (6%) 27 ER+ (75%) – 24 PR+ (67%) |
4.5 years in the control arm 7.3 years in the experimental arm 4.7 years in all patients |
Control arm: systemic therapy Experimental arm: systemic therapy plus intrathecal liposomal cytarabine 50 mg every 14 days for 2 months (5 total injections) followed by monthly injection of 50 mg until PD |
Yes | No significant differences in the incidence of severe (G3 or higher) AEs between the two groups | Median LM PFS in the ITT: 2.2 (control) vs 3.8 (experimental) (HR 0.61; p=0.04) Clinical LM response in the ITT: improvement 3% vs 17%; stabilization 81% vs 72%, deterioration 11% vs 11%, missing 5% vs 0% Radiological LM response in the ITT: PR 8% vs 19%, SD 32% vs 56%, PD 30% vs 14%, missing 30% vs 11% |
Overall PFS in the ITT: 2.0 months (control) vs 2.4 months (experimental) (HR 0.66; p=0.09) OS in the ITT: 4.0 months (control) vs 7.3 months (experimental) (HR 0.85; p=0.051) |
BC, breast cancer; CAF, cyclophosphamide, doxorubicin, 5-fluorouracil; CMF, cyclophosphamide, methotrexate, 5-fluorouracil; FEC, 5-fluorouracil, epidoxorubicin, cyclophosphamide; IF/RT, involved field radiotherapy; IT, intrathecal; MTX, methotrexate.