Lurbinectedin Shows Promise For Platinum-Resistant Ovarian Cancer

Patients with advanced ovarian cancer may benefit from lurbinectedin therapy, especially those with platinum-resistant disease

medwireNews: A phase II proof-of-concept study indicates that the active transcription inhibitor lurbinectedin may have antitumour activity in patients with advanced ovarian cancer that is resistant or refractory to platinum-based chemotherapy.

“The poor prognosis of the patient population in this phase II trial needs to be borne in mind: 37% of patients had platinum-refractory disease, and 35% had previously received one prior chemotherapy line after confirmation of platinum resistant/refractory disease”, the researchers say.

In all, 52 patients were treated with lurbinectedin 7 mg every 3 weeks, including 22 patients in the first exploratory stage of the trial and 30 patients in the second randomised stage of the study.

 

The primary endpoint was met, with an objective response rate of 23% for the 52 patients taking lurbinectedin, report Andrés Poveda, from Instituto Valenciano de Oncología in Spain, and co-workers.

This included one RECIST-defined complete response, nine RECIST-defined partial responses and two Gynecologic Cancer InterGroup-defined partial responses.

By contrast, none of the 29 patients who were randomly assigned to receive an investigator’s choice of daily or weekly topotecan regimen in the second stage of the study achieved an objective response.

Patients with an objective response to lurbinectedin had a median duration of response of 4.6 months, with 23% of responses lasting at least 6 months.

And the researchers highlight in the Annals of Oncology that 10 of the 12 responses were among the 33 patients in the study who had platinum-resistant disease, defined as having had a relapse or progression within 6 months of their last platinum-based chemotherapy dose.

In addition, an objective response occurred in six of the 18 patients for whom lurbinectedin was second-line after becoming resistant or refractory to platinum-based chemotherapy and also in three of the six patients who had previously used the angiogenesis inhibitor bevacizumab .

Describing the activity of lurbinectedin in platinum-resistant patients as “remarkable”, the researchers say that the agent is now under investigation in the “pivotal” CORAIL study of this patient subgroup.

However, lurbinectedin was associated with grade 3 or 4 neutropenia in 85% of patients and grade 3 or 4 thrombocytopenia in 33%, with 21% of patients who experienced febrile neutropenia requiring granulocyte-colony stimulating factor prophylaxis.

Fatigue was the most common nonhaematological treatment-related adverse event, affecting 77% of patients, including grade 3 symptoms in 35%. One patient developed grade 3 rhabdomyolysis but dose reduction was not required.

Andrés Poveda et al cite recent study findings suggesting that grade 3 or 4 neutropenia and thrombocytopenia were more common in patients with a low body surface area (BSA). “BSA-based dosing (4.0 mg/m2) should now be adopted and the recommended dose reduced for future studies to improve safety”, they suggest.

Reference

Poveda A, del Campo JM, Ray-Coquard I,et al. Phase II randomized study of PM01183 versus topotecan in patients with platinum-resistant/refractory advanced ovarian cancer. Ann Oncol; Advance online publication 20 March 2017. DOI: https://doi.org/10.1093/annonc/mdx111

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