Activity of Lurbinectedin (PM01183) as Single Agent and in Combination in Patients with Endometrial Cancer.
Background:
Lurbinectedin (L) is a New Anticancer Drug that blocks trans-activated transcription, induces DNA double-strand breaks and modulates the tumor microenvironment.
Advanced endometrial cancer (EC) is an unmet medical need.
Methods:
Activity in EC patients was reviewed in 3 trials: a phase IB study of lurbinectedin combined with doxorubicin (L+DOX), a phase I study of PM combined with paclitaxel (L+TAX) and a phase II single-agent basket trial (L). Baseline characteristics, safety and efficacy were analyzed.
Results:
97 patients were evaluated: 34 (2 cohorts) with L+DOX, 11 with L+TAX and 52 with L. Median age was similar in the 3 studies. Endometrioid was the most frequent histology. Median (range) of prior chemotherapy lines for advanced disease was: L+DOX, 1(0-2); L+TAX, 2(1-3); L, 1(0-2). Responses were observed in the 3 studies (see table). Main adverse event was myelosuppression (grade 3-4 Neutropenia/thrombocytopenia/febrile neutropenia: L+DOX Cohort A, 94%/26%/40%; L+DOX Cohort B, 79%/10%/16%; L+TAX, 54%/0%/0%; L, 33%/6%/6%).
Non-hematological toxicity was mostly grade 1-2: fatigue, nausea and vomiting, and transaminase increase.
Conclusions:
Lurbinectedin is active as single agent and in combination in patients with advanced EC, with remarkable activity in terms of response rate, duration of response and PFS when combined with doxorubicin. Safety was acceptable in L+DOX Cohort B, L+TAX and L, and myelosuppression was well managed.
| Response (evaluable patients) | L+DOX (q3wk) | L+TAX (q3wk) | L alone (q3wk) | |
|---|---|---|---|---|
| Cohort A L 3-5 mg FD D1 + DOX 50 mg/m2 D1 (n=14) | Cohort B L 2 mg/m2 D1 + DOX 40 mg/m2 D1 (n=18) | L 2.2 mg/m2 D1 + TAX 80 mg/m2 D1 & D8 (n=11) | L 3.2 mg/m2 D1 (n=40) | |
| CR | 2 (14%) | - | - | 1 (3%) |
| PR | 2 (14%) | 8 (44%) | 3 (27%) | 4 (10%) |
| ORR | 4 (28%) | 8 (44%) | 3 (27%) | 5 (12.5%) |
| SD | 8 (57%) | 7 (39%) | 2 (18%) | 15 (38%) |
| PD | 2 (14%) | 3 (16%) | 6 (55%) | 20 (50%) |
| DCR | 9 (85%) | 15 (83%) | 5 (45%) | 20 (50%) |
| DOR (mo) | 19.5 | 6.8 | 6.1 | 4.3+ |
| PFS (mo) | 7.8 | 7.7 | 1.9 | 2.5+ |
CR, complete response; D, day; DCR, disease control rate; DOR, duration of response; DOX, doxorubicin; FD, flat dose; mo, months; ORR, overall response rate; PD, progressive disease; PFS, progression free survival; PM, PM1183, PR, partial response; q3wk, every 3 weeks; SD, stable disease; TAX, paclitaxel.