Biweekly Act-D vs multiday MTX: Which is more effective against GTN?

Biweekly single-dose actinomycin-D (Act-D) is superior to 8-day methotrexate (MTX) regimen as first-line single-agent chemotherapy in patients with low-risk gestational trophoblastic neoplasia (GTN), as shown by a study presented at SGO 2025.

Act-D also demonstrates faster remission but results in a higher incidence of nausea, vomiting, and hair loss relative to MTX.

“Both regimens had mild, reversible effects on anti-Müllerian hormone (AMH) levels and fertility outcomes during follow-up,” said lead author Dr Fang Jiang from Peking Union Medical College Hospital, Beijing, China.

Jiang and her team conducted a multicentre, randomized controlled trial involving patients with FIGO stage I‒III, low-risk GTN (FIGO score 0‒4) across eight centres in China. A total of 228 eligible patients were randomly allocated in a 1:1 ratio to either Act-D (1.25 mg/m2, maximum 2 mg, every 14 days) or MTX-folinic acid (FA; 50 mg intramuscularly on days 1, 3, 5, and 7, with leucovorin rescue of days 2, 4, 6, and 8) between 27 September 2020 and 18 June 2024.

Treatment was administered until β-hCG normalization, followed by 2 to 3 consolidation cycles. Jiang and colleagues then assessed the primary outcomes, namely complete remission (CR) rates for single-agent chemotherapy and overall CR rates. They also examined the time to CR, chemotherapy cycles, toxicity, and changes in AMH. Adverse events were graded per CTCAE v5.0.

Patients in the Act-D arm achieved significantly higher CR rates (72.8 percent vs 54.4 percent; p=0.0038) and showed faster remission (8.75 vs 10.24 weeks; p=0.0296) than those in the MTX regimen arm. Both treatment groups attained 100-percent CR rates following combination chemotherapy for resistance cases. [SGO 2025, abstract LBA04]

Safety profile

Adverse events (AEs) reported were mostly mild in severity (grade 1‒2). However, grade ≥2 nausea and vomiting occurred more frequently in the Act-D arm (49.1 percent vs 18.4 percent; p<0.001), as did hair loss (6.1 percent vs 0 percent; p=0.0142), than in the MTX arm.

On the other hand, patients on MTX had more frequent alanine aminotransferase (ALT) elevation than their counterparts on Act-D (13.2 percent vs 4.4 percent; p=0.0192). Haematologic toxicities were mild across the two regimens.

More severe AEs (grade 3) rarely occurred but were more common among patients treated with Act-D during the single-agent chemotherapy phase. Grade 3 nausea and vomiting occurred in 14 percent of patients in the Act-D arm relative to 4.4 percent in the MTX arm (p=0.0118).

Furthermore, transient AMH reductions occurred in both treatment regimens (median decrease: 0.24 for MTX vs 0.84 for Act-D; p=0.0123 and p<0.0001, respectively). Both recovered within 6 months.

After a median follow-up of 28.5 months (November 2024), the rates of recurrence were low and similar between the two groups (0.88 percent for MTX vs 1.75 percent for Act-D; p>0.05). All recurrent cases achieved remission following salvage therapy.

Notably, both groups had favourable fertility outcomes. Several patients achieved successful pregnancies, including full-term deliveries, according to the researchers.

“Both regimens are effective options, with treatment selection based on patient priorities,” Jiang said.

“Longer follow-up is needed to fully assess the long-term impact of treatment on reproductive health,” she added.