Does the progression‐free interval after primary chemotherapy predict survival after salvage chemotherapy in advanced and recurrent endometrial cancer?

Abstract

BACKGROUND: This study evaluated whether progression-free interval (PFI) following primary chemotherapy (PCT) was predictive of overall survival (OS) after second-line chemotherapy in advanced/recurrent endometrial cancer (EC). METHODS: This is a pooled analysis of patients who recurred after PCT and were treated with second-line chemotherapy on Gynecologic Oncology Group trials. PFI-1 measured from initiation of PCT to recurrence or treatment-free interval (TFI) measured from completion of PCT to initiation of second-line chemotherapy was evaluated in relation to clinical outcomes. RESULTS: A total of 586 patients treated on 5 phase 3 PCT protocols were included. Baseline factors in primary setting associated with clinical outcome after PCT were also predictive of OS after second-line chemotherapy, including race, Gynecologic Oncology Group performance status, grade, and prior radiation therapy (P < .01). PFI-1 was the most significant factor predictive of survival after second-line chemotherapy, with a 30% reduction in the risk of death for PFI-1 >6 months compared with 6 months (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.59-0.84 [P < .0001]) and median OS after second-line chemotherapy of 10 versus 5 months. A total of 275 patients treated on 9 phase 2 second-line chemotherapy protocols were also evaluated, and TFI >3 months was associated with a 25% reduction in the risk of death (HR, 0.75; 95% CI,) and median OS after second-line chemotherapy of 10 versus 7 months compared with TFI 3 months. The tumor response to second-line chemotherapy was 9.6% versus 5.8%; the difference was not statistically significant. CONCLUSIONS: Time to recurrence after PCT is predictive of survival after recurrence in advanced/recurrent EC. However, there is no evidence that this variable can be used in selecting salvage chemotherapy.

Clinical outcome of recurrent endometrial cancer: analysis of post-relapse survival by pattern of recurrence and secondary treatment

“…Median survival after endometrial cancer recurrence in this study was 21 months, consistent with previous descriptions of the dismal prognosis of recurrent endometrial cancer 5 7–10 12 23. Yet, post-relapse survival was significantly influenced by the pattern of recurrence, with the best prognoses found in patients with lymphatic recurrences and the worst in those with mesothelial or mixed recurrence.…”

“…This finding indicates that single pathway recurrent endometrial cancer may be less deregulated and more biologically similar to the primary tumor than multiple pathway recurrent endometrial cancer. In this context it is important to highlight the controversial prognostic role of time to recurrence: few studies have suggested that a time to recurrence longer than 6–12 months is associated with better post-relapse survival 7 8. In our multivariate analysis, time to recurrence was not a significant predictor of post-relapse survival in the overall population or in sub-group analyses, suggesting that, unlike ovarian cancer, a short time to recurrence in endometrial cancer does not necessarily indicate treatment resistance, but may be related to the persistence of microscopic disease after primary treatment.…”

“…Few previous studies have investigated the relationship between clinical patterns of relapse and the clinico-pathologic characteristics of primary disease 5. Moreover, data regarding the clinical outcomes of recurrent endometrial cancer in terms of patterns of presentation and secondary treatment are inconclusive 7–12. A more detailed understanding of the prognoses associated with various recurrences of endometrial cancer is necessary to improve primary as well as secondary treatment.…”

ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: Diagnosis, Treatment and Follow-up

“…Although various regimens have been evaluated in this setting,189–192 no randomised trials have been published. Therefore, no specific regimen can be recommended as a standard of care for second line chemotherapy.…”

Platinum-free Interval in Second-line Chemotherapy for Recurrent Cervical Cancer

“…8 That study also suggested that TFI is an important indicator when single agents are used as second-line chemotherapy for endometrial cancer. These findings raise the possibility that TFI or PFI could be used in selecting the second-line chemotherapy regimen in cervical cancer.…”