Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer delays third-line chemotherapy and prolongs the platinum-free interval

Abstract

Background: OVA-301 is a large randomized trial that showed superiority of trabectedin plus pegylated liposomal doxorubicin (PLD; CentoCor Ortho Biotech Products L.P., Raritan, NJ, USA). over single-agent PLD in 672 patients with relapsed ovarian cancer, particularly in the partially platinum-sensitive subgroup [platinum-free interval (PFI) of 6–12 months]. This superiority has been suggested to be due to the differential impact of subsequent (platinum) therapy.Patients and methods: A detailed analysis of subsequent therapies and survival outcomes in the overall population and in the subsets according to platinum sensitivity was therefore conducted.Results: Similar proportions of patients received subsequent therapy in each arm (76% versus 77%), including further platinum-based regimens (49% versus 55%). Patients in the trabectedin/PLD arm received subsequent chemotherapy at a later time (median delay 2.5 months versus PLD arm). Overall survival from subsequent platinum was significantly prolonged in the partially platinum-sensitive disease subset (hazard ratio = 0.63; P = 0.0357).Conclusion: The superiority of trabectedin/PLD over single-agent PLD in OVA-301 cannot be explained by differences in the extent or nature of subsequent therapies administered to these patients. On the other hand, these exploratory analyses support the hypothesis that the enhanced survival benefits in the partially platinum-sensitive subset might be due to an extended PFI leading to longer survival with subsequent platinum.

Revisiting the Complexity of the Ovarian Cancer Microenvironment—Clinical Implications for Treatment Strategies

“…Previously, a randomized phase III clinical trial, OVA-301, assessed the efficacy of Trabectedin in combination with pegylated lysosomal doxorubicin (PLD) compared with PLD alone, in patients with recurrent EOC following platinum-based chemotherapy failure (35). The authors concluded that Trabectedin/PLD combination improved progression-free survival and overall response rate in patients displaying a platinum-free interval of more than 6 months, compared with patients receiving PLD alone (35,36). In a more recent preclinical study, it was shown that Trabectedin inhibited tumor growth in xenograft models of clear cell carcinoma of the ovary, which further shows its potential as either a first-line or second-line therapy for certain subgroups of ovarian neoplasms (37).…”

Effective treatment of a patient with stage�IV ovarian cancer: A case report

“…The patient was enrolled in the OVA-301 study and benefited markedly with prolonged progression-free survival (>1 year). Therefore, patients with ovarian cancer relapse may be encouraged to participate in clinical trials (9,10). CA125 testing served a key role in disease follow-up.…”

“…The patient's CA125 level was measured at 25.69 U/ml following this course of chemotherapy, until relapse, increasing to 262.50 U/ml after 3 months. After 18 days of treatment with 1 cycle of lobaplatin (50 mg) and irinotecan (280 mg), the patient developed severe bone marrow suppression [white blood cells (WBC), 1.72x10 9 /l; platelets (PLT), 7x10 9 /l], high fever and diarrhea. However, the CA125 levels returned to normal at 28.51 U/ml.…”

Long-term effect of pegylated liposomal doxorubicin in recurrent platinum-resistant ovarian cancer: а clinical case

“…Чувствительность реци-дивов РЯ к самым эффективным при этом заболевании препаратам -производным платины -имеет прямую корреляционную зависимость от длительности беспла-тинового интервала. Данные экспериментов проде-монстрировали, что напряженность резистентности клеток карциномы яичников к производным платины не является постоянной величиной: механизмы рези-стентности наиболее активны сразу после воздействия производного платины, но в последующем при отсут-ствии экспозиции опухолевых клеток с платиной ак-тивность этих механизмов ослабевает [18]. Данные экспериментов имеют косвенное подтверждение в кли-нической практике, что продемонстрировано в под-анализе исследования OVA-301.…”