Quality of life (QoL) and symptom benefit should be accepted by clinicians and regulators as additional coprimary endpoints in clinical trials of chemotherapies for platinum-resistant and refractory ovarian cancer, according to a group of experts.
These measures are "the most important aims of treatment" in these patients because improvements in overall and progression-free survival (OS and PFS) have hit a ceiling in trial after trial of chemotherapies, say Michael Friedlander, MD, and colleagues from the Prince of Wales Hospital, in New South Wales, Australia. The group published a letter on May 13 in the Journal of Clinical Oncology.
The conventions of OS and PFS should remain in place in trials but be supplemented by these "other meaningful ways to measure treatment benefit," they say.
The letter writers are responding to a recent study and accompanying editorial published in the journal that related to 2 chemotherapies being compared in a phase 3 trial in this patient population (J Clin Oncol. 2013;30:3841-3847). In the trial, patupilone and liposomal doxorubicin produce the same PFS (3.7 months median) and a comparable OS (13.2 vs 12.7 months).
In short, Dr. Friedlander and his colleagues believe that palliative chemotherapy should be also evaluated for improvement in quality of life and symptoms and that those measures should count in the drug approval process.
There needs to more than one "route to registration of new agents," they say about the need for regulatory changes.
Agreed, said David Spriggs, MD, of Memorial Sloan-Kettering Cancer Center, in New York City. He served as the editorialist on the study of patupilone vs liposomal doxorubicin and, in turn, responded to the Australian letter about his essay and the trial.
"It is essential," Dr. Spriggs writes, that "comfort, function and quality of life have a place in the commercialization pathway."
Both he and the Australians believe that "today's development process seems excessively focused on duration of life."
Patients with recurrent ovarian cancer…are incurable with today's therapies.
"Patients with recurrent ovarian cancer (platinum-sensitive or resistant) are incurable with today's therapies," he writes, adding that life expectancy is 12 to 18 months.
The problem of poor prognosis is not limited to ovarian cancer, adds Dr. Spriggs. "In these settings…a patient's goal is to enjoy a comfortable and highly enjoyable life for as long as possible," he says.
But accommodating QoL as a primary endpoint in a drug approval trial "has historically been quite difficult," Dr. Spriggs adds. "This is a reflection of the fact that QoL can be slippery when reduced to practice."
Dr. Friedlander and colleagues report that there is a major clinical trial under way (Gynecologic Cancer Intergroup Symptom Benefit Trial) that is seeking to "validate an instrument to measure symptom benefit that can be applied to clinical trials." The trial is also seeking to identify subsets of patients who are most likely to benefit from palliative chemotherapy.
The authors have disclosed no relevant financial relationships.
Citation: New Endpoints Proposed for Chemotherapy in Ovarian Cancer. Medscape. Jun 18, 2013.