Endometrial Ca: Progression-Free Interval Predicts Survival, 'Limited' Clinical Value


SAN ANTONIO — The length of time between the starts of primary and secondary treatment for advanced or recurrent endometrial cancer is a statistically significant predictor of a woman's risk of death 6 months after resuming treatment, according to a review of phase III trials conducted over the last 20 years.

A progression-free interval lasting more than 6 months reduced the risk of death by 30% in the Gynecologic Oncology Group (GOG) studies. The finding was statistically significant with a P value of .0001, but investigators concluded it had “limited” clinical value. Compared with women whose disease progressed within 6 months or less, patients gained about 3 months of life when they went longer before restarting treatment. Moreover, platinum sensitivity did not make much difference in the impact of second-line treatments on survival.

“Ten months versus 7 months—that's not a very useful prognostic indication,” lead investigator Kathleen M. Moore said in an interview, referring to the median probability of survival after second-line treatment with the longer progression-free interval versus a shorter span. “For endometrial cancer, it really doesn't change what you are going to do for that patient. It doesn't change how you are going to counsel that patient about progression.”

Dr. Moore of the University of Oklahoma, Oklahoma City, presented the results at the annual meeting of the Society of Gynecologic Oncologists.

The ancillary data analysis compared outcomes relative to progression-free intervals among 586 women who participated in GOG protocols 107, 122, 139, 163, and 177, which tested a variety of chemotherapy regimens. The women had a median age of 64 years, and nearly two-thirds had recurrent disease in this first part of the study. Most received platinum-based regimens as first-line therapy; their median progression-free interval was 6.7 months.

Investigators also reviewed treatment-free intervals from completion of the first regimen to progression for 275 women in the GOG protocol 129 series of trials. This group's median age was 66 years, and 89% of the women had been given platinum-based regimens as first-line therapy.

The women in this part of the study had a median treatment-free interval of 2.9 months. A treatment-free interval greater than 3 months was associated with a 25% reduction in risk of death (P = .014), but the investigators again saw little clinical value. Median survival from the start of therapy was 10.22 months with the longer treatment-free interval and 7.39 months for those who stayed off treatment for less than 3 months.

The findings were “very disappointing,” Dr. Moore said. Investigators had hoped to see a difference comparable to ovarian cancer, a disease in which some women gain 2 years of life, with median survival improving from 12 months to 36 months, if they remained progression free for more than 6 months after first-line treatment. She attributed the differences in predictive value of progression-free interval in part to underlying differences in response to first-line therapy. Women with ovarian cancer are typically in remission after completing their first chemotherapy, she said. This is not the case in women with endometrial cancer: “Only 15% had a complete clinical response—the majority finished their first chemotherapy with measurable disease.”

Moreover, the second-line treatments that can significantly prolong survival in ovarian cancer are lacking in endometrial cancer, she said, describing continued drug development as key to improving survival. Dr. Moore disclosed no conflicts of interest.

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