NEW RESEARCH RESULTS: Trabectedin Plus Doxil in Relapsed Ovarian Cancer

lindaprocopio

These research posts are technical and hard to understand, but I post them because they do suggest options worth mentioning to your oncologists. Translation of some of the abbreviations they use in cancer research:
OS = overall survival
PFS = progression free survival (either on or off treatment, not necessarily remission)
PFI = platinum free interval (I THINK this is the time since you last had carboplatin or cisplatin; ???)
Pegylated Liposomal Doxorubicin = Doxil
Trabectedin = also known as "ecteinascidin 743" or ET-743

This is brand-new, July 2010:

Trabectedin Plus Pegylated Liposomal Doxorubicin in Relapsed Ovarian Cancer Delays Third-Line Chemotherapy and Prolongs the Platinum-Free Interval
Ann Oncol. 2010 Jul 19;[Epub Ahead of Print], SB Kaye, N Colombo, BJ Monk, S Tjulandin, B Kong, M Roy, S Chan, E Filipczyk-Cisarz, H Hagberg, I Vergote, C Lebedinsky, T Parekh, P Santabárbara, YC Park, A Nieto, A Poveda

TAKE-HOME MESSAGE
Trabectedin plus pegylated liposomal doxorubicin (PLD) was associated with improved survival when compared with PLD alone in patients with relapsed ovarian cancer. This may be attributed to extension of the platinum-free interval in patients with partially platinum-sensitive disease.

STUDY IN CONTEXT
Trabectedin is a marine-derived antineoplastic agent active against multiple tumor types, including soft-tissue sarcoma and ovarian cancer.

Combination therapy with trabectedin plus pegylated liposomal doxorubicin (PLD) was found to be superior to PDL alone for patients with relapsed ovarian cancer in the open-label, multicenter, randomized, phase III OVA-301 trial. In this study, 672 patients received either PLD 30 mg/m2 followed by trabectedin 1.1 mg/m2 every 3 weeks or PLD 50 mg/m2 every 4 weeks. The benefit of trabectedin plus PLD was particularly pronounced in the subgroup of patients who were partially platinum sensitive, ie, who had a platinum-free interval (PFI) of 6 to 12 months. Compared with PLD alone, the combination regimen resulted in a 15% decrease (hazard ratio [HR], 0.85; P = .092) in the risk of death for all randomized patients but a 41% decrease in the risk of death for the partially platinum-sensitive subset (HR, 0.59; P = .0015). The median length of overall survival (OS) was 23.0 months in the combination arm vs 17.1 months in the PLD arm. The median difference of 5.9 months was greater than the median difference in PFS.

To further investigate whether the safety and efficacy of trabectedin might be attributed to subsequent platinum therapy, researchers conducted an exploratory analysis of all subsequent therapies and survival outcomes in the overall population and in the platinum-sensitive subsets, with an additional year of follow-up. The primary endpoint was OS. Optimal treatment for patients with platinum-sensitive disease is currently controversial.

Subsequent therapies were administered to 77% of patients completing PLD alone and to 76% of all trabectedin/PLD patients from the OVA-301 trial, although only 49% of the patients in the combination arm received platinum-based regimens, compared with 55% in the other arm.

Cytoreductive surgery was the subsequent therapy in 4% of PLD patients vs 6% of trabectedin/PLD patients; subsequent radiotherapy was received by 7% of the combination-therapy group vs 4% of the PLD group. Subsequent platinum-based chemotherapy was administered to 36% of platinum-resistant patients, 57% of partially platinum-sensitive patients, and 64% of platinum-sensitive patients.

Median OS was 14.9 months in each treatment arm regardless of the timing of the subsequent platinum-based therapy. The median time to subsequent platinum therapy was 10.3 months in the trabectedin/PLD arm vs 7.6 months in the PLD arm. This difference of 2.7 months was not significantly different from the 2.5-month interval in the overall population before the receipt of all other types of subsequent therapies (HR, 0.80; 95% CI, 0.64–0.99; P = .0361).
Subsequent treatment with platinum-based chemotherapy prolonged OS in the partially platinum-sensitive patients by 3.5 months in the trabectedin/PLD arm (13.3 vs 9.8 months), reducing the risk of death by 37% (HR, 0.63; P = .0357). Among partially platinum-sensitive patients receiving platinum as first subsequent therapy, receipt of platinum therapy was delayed by a median of 4 months (HR, 0.61; P = .0203); OS from the time of receiving first subsequent therapy with platinum was significantly extended, by a median of 8.7 months (HR, 0.54; P = .0169).

Overall, platinum rechallenge was received by 57% of patients with partially platinum-sensitive disease and by 64% of patients with fully platinum-sensitive disease. The group with partially platinum-sensitive disease responded less to further platinum therapy.
The investigators speculated that enhanced survival benefits with trabectedin/PLD over single-agent PLD in OVA-301, especially in patients with partially platinum-sensitive disease, may be due to an extension of the PFI. There was a delay of 6 months for all trabectedin/PLD patients who received subsequent platinum at any time following the OVA-301 trial and 2.7 months for these patients who received subsequent platinum compared with patients in the PLD arm.

Treatment of these platinum-sensitive patients with trabectedin/PLD, a nonplatinum combination, resulted in longer survival after the start of subsequent platinum-based chemotherapy. This finding was probably attributed to extension of the PFI.