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Does the progression-free interval after primary chemotherapy predict survival after salvage chemotherapy in advanced and recurrent endometrial cancer?†‡
A Gynecologic Oncology Group ancillary data analysis
Article first published online: 24 AUG 2010
Copyright © 2010 American Cancer Society
Volume 116, Issue 23, pages 5407–5414, 1 December 2010
How to Cite
Moore, K. N., Tian, C., McMeekin, D. S., Thigpen, J. T., Randall, M. E. and Gallion, H. H. (2010), Does the progression-free interval after primary chemotherapy predict survival after salvage chemotherapy in advanced and recurrent endometrial cancer?. Cancer, 116: 5407–5414. doi: 10.1002/cncr.25480
Presented at the Gynecologic Oncology Group Meeting, Garden Grove, California, January 22-25, 2009, and as a plenary presentation at the Society of Gynecologic Oncologists Annual Meeting, San Antonio, Texas, February 5-8, 2009.
The following Gynecologic Oncology Group member institutions participated in the primary treatment studies: Wake Forest University School of Medicine, Columbus Cancer Council, University of California Medical Center at Irvine, Duke University Medical Center, Wayne State University, Indiana University Medical Center, University of Kentucky, Washington University School of Medicine, Abington Memorial Hospital, University of Iowa Hospitals and Clinics, Tufts-New England Medical Center, University of Mississippi Medical Center, Milton S. Hershey Medical Center, Rush-Presbyterian-St. Luke's Medical Center, Albany Medical College, University of Texas Southwestern Medical Center at Dallas, Community Clinical Oncology Program, University of Oklahoma, University of Minnesota Medical School, University of Virginia, Cleveland Clinic Foundation, University of Alabama at Birmingham, Colorado Gynecologic Oncology Group, University of North Carolina School of Medicine, University of Massachusetts Medical School, Fox Chase Cancer Center, Women's Cancer Center, State University of New York at Stony Brook, Medical University of South Carolina, Johns Hopkins Oncology Center, Cooper Hospital/University Medical Center, University of Chicago, Walter Reed Army Medical Center, Tampa Bay Cancer Consortium, University of Rochester Medical Center, Eastern Pennsylvania Gynecology/Oncology Center, Tacoma General Hospital, Thomas Jefferson University Hospital, Case Western Reserve University, University of Cincinnati, University of Pennsylvania Cancer Center, Gynecologic Oncology Network, Georgetown University Hospital, Mayo Clinic, Oregon Health Sciences University, University of Miami School of Medicine, University of California at Los Angeles, State University of New York Upstate Medical Center, Eastern Virginia Medical School, The University of Texas M. D. Anderson Cancer Center, Ellis Fischel Cancer Center, State University of New York Downstate Medical Center, Emory University Clinic, University of Southern California at Los Angeles, Stanford University Medical Center, Memorial Sloan-Kettering Cancer Center, University of Washington, North Shore University Hospital, and Long Island Jewish Medical Center.
- Issue published online: 23 NOV 2010
- Article first published online: 24 AUG 2010
- Manuscript Accepted: 11 MAY 2010
- Manuscript Revised: 8 MAY 2010
- Manuscript Received: 16 DEC 2009
- endometrial cancer;
- Gynecologic Oncology Group;
- ancillary data analysis;
- salvage chemotherapy
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).
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.
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, 0.57-0.97 [P = .030]) 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.
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. Cancer 2010. © 2010 American Cancer Society.
Of all the gynecologic malignancies, endometrial cancer has undergone the most dramatic shift in management over the past several years. Key among these is the identification of active chemotherapy regimens and their utilization in a first-line setting for what was once felt to be chemotherapy-resistant disease. There have been several randomized studies performed by the Gynecologic Oncology Group addressing the issue of optimal therapy for patients with advanced/recurrent disease who have received no prior chemotherapeutic regimen. Gynecologic Oncology Group protocol 107 evaluated doxorubicin alone versus doxorubicin plus cisplatin (AP) and found the latter to be superior in terms of response rate (RR) (25% vs 42%; P = .004) and progression-free survival (PFS) (3.8 vs 5.7 months; hazard ratio [HR] 0.74; 95% confidence interval [CI], 0.58-0.94), although no difference in overall survival (OS) was observed (9.0 vs 9.2 months).1 In Gynecologic Oncology Group protocol 122, chemotherapy with doxorubicin plus cisplatin was compared with whole abdominal radiation (WAR) therapy in patients with stage III-IV endometrial cancer with <2-cm residual disease. In that trial, doxorubicin plus cisplatin produced superior PFS (50% vs 38% at 5 years; P = .007) and OS (55% vs 42% at 5 years; P = .004) compared with WAR.2 This established chemotherapy as the standard of care for advanced stage disease as well as disseminated recurrent disease. Phase II data demonstrated that paclitaxel had significant single-agent activity, with an RR of 36% in advanced/recurrent endometrial cancer.3 This finding contributed to the development of Gynecologic Oncology Group protocol 163, which compared doxorubicin and paclitaxel versus doxorubicin plus cisplatin.4 This trial failed to demonstrate a significant difference in RR, PFS, or OS between the 2 arms, and doxorubicin plus cisplatin remained the standard of care. Gynecologic Oncology Group protocol 177 compared doxorubicin plus cisplatin versus doxorubicin plus cisplatin on Day 1 followed by paclitaxel on Day 2; the latter was superior to doxorubicin plus cisplatin in terms of overall RR (57% vs 34%; P < .01) and median PFS (8.3 vs 5.3 months; P < .01), and for the first time OS was superior, with a median of 15.3 (doxorubicin plus cisplatin on Day 1 followed by paclitaxel on Day 2) versus 12.3 months (doxorubicin plus cisplatin) (P = .037).5 With current, completed trials, the most efficacious regimen for primary treatment of advanced or recurrent endometrial cancer is doxorubicin plus cisplatin on Day 1 followed by paclitaxel on Day 2, with a complete clinical RR of 22% and a median PFS of 8 months, as reported from Gynecologic Oncology Group protocol 177. Clearly, the majority of patients with either advanced or recurrent endometrial cancer will progress after first-line chemotherapy. Unfortunately, there are limited options to treat persistent or recurrent disease after first-line chemotherapy, and no standard regimen has yet been defined. In an effort to identify active agents in endometrial cancer, the Gynecologic Oncology Group has developed a phase 2 queue evaluating novel cytotoxic agents (Gynecologic Oncology Group 129 series) for patients with measurable, recurrent/persistent disease who have received 1 prior chemotherapy regimen. To date, there have been 9 published Gynecologic Oncology Group 129 series studies. By using response as the primary endpoint, only paclitaxel produced sufficient responses (>25%) to warrant further evaluation in a phase 3 setting.6 Oxaliplatin and liposomal doxorubicin produced modest activity at 13% and 9% RR, respectively, but have not been further evaluated in this disease.7, 8 The Gynecologic Oncology Group series 229 is also a phase 2 trial program, which evaluates biologic (noncytotoxic) agents in the second-line treatment of advanced/recurrent endometrial cancer. Of the 6 studied agents, only the study of thalidomide (229-B) has been published, showing minimal activity, with 8% of patients remaining progression-free at 6 months.9
In ovarian cancer treatment, the concept of the platinum-free interval exists as a marker for prognosis after recurrence.10, 11 In recurrent ovarian cancer management, the platinum-free interval is used to distinguish dichotomous groups of patients based on prognoses and probability of response to salvage agents. Furthermore, the length of the platinum-free interval is pivotal in the structure and design of many collaborative group trials in the treatment of recurrent ovarian cancer. Given the limited options available to patients with persistent/progressive endometrial cancer after first-line therapy, this study sought to evaluate whether there is an interval similar to ovarian cancer to define chemosensitive or resistant tumor in prediction of response to second-line chemotherapy and OS from time of recurrence.
MATERIALS AND METHODS
This study was a pooled data analysis of patients with advanced/recurrent endometrial cancer treated on 1 of 5 Gynecologic Oncology Group randomized phase 3 chemotherapy trials: Gynecologic Oncology Group 107 compared doxorubicin (60 mg/m2) to doxorubicin plus cisplatin (60 mg/m2 and 50 mg/m2); Gynecologic Oncology Group 122 Arm 2 used doxorubicin plus cisplatin (60 mg/m2 and 50 mg/m2); Gynecologic Oncology Group 139 compared standard timed doxorubicin plus cisplatin (60 mg/m2 and 60 mg/m2) to a circadian timed administration of the same combination; Gynecologic Oncology Group 163 compared doxorubicin plus cisplatin (60 mg/m2 and 50 mg/m2) to doxorubicin and paclitaxel (50m/m2 and 150 mg/m2, over 24 hours); and Gynecologic Oncology Group 177 compared doxorubicin plus cisplatin (60 mg/m2 and 50 mg/m2) to doxorubicin plus cisplatin on Day 1 followed by paclitaxel on Day 2 (160 mg/m2, Day 2, 45 mg/m2 and 50 mg/m2, Day 1). Results of each of these studies have been presented elsewhere.1, 2, 4, 5, 12 Eligibility criteria were similar for each study, with the exception of Gynecologic Oncology Group 122, which permitted patients with <2 cm residual, stage III/IV disease. Otherwise, all patients were to have measurable disease and could not have received prior cytotoxic chemotherapy. Patients were required to have stage III-IV or recurrent endometrial cancer and a poor potential for cure from radiation therapy or surgery alone or in combination. Tumor samples from all subjects underwent histologic confirmation by the Pathology Committee of the Gynecologic Oncology Group. All 5 studies required that patients be followed similarly with serial examinations and imaging studies every 3 months for 2 years, then every 6 months thereafter. The factors associated with treatment response and clinical outcome have been previously evaluated.13, 14
All patients who participated in the above protocols except the WAR arm of Gynecologic Oncology Group122 were reviewed. Patients who progressed after primary chemotherapy (PCT) and subsequently received second-line chemotherapy were identified and included in this study. Those patients who received no additional therapy at recurrence were excluded from this analysis. A pre-evaluation found that this group of patients usually had a very short survival after disease recurrence, and we assume that they did not receive additional chemotherapy, likely because of their poor performance status and prognosis at recurrence. Progression-free interval (PFI-1) was measured from the date of randomization of primary treatment to the time of disease recurrence. Primary and salvage treatment were classified into platinum-based and nonplatinum chemotherapies.
A second dataset was also explored to evaluate the impact of the interval after PCT on treatment outcome after second-line chemotherapy. Data from the Gynecologic Oncology Group phase 2 cytotoxic series 129, including Gynecologic Oncology Group 129 B, C, E H, I, J, K, L, and M, were analyzed. Patients enrolled in these studies were reviewed to determine whether the treatment-free interval (TFI) can be used to predict tumor response, PFS, and OS from time of second-line chemotherapy.6-8, 15-20 Eligibility criteria were similar for all Gynecologic Oncology Group 129 series studies. Patients were required to have recurrent or persistent endometrial carcinoma refractory to curative therapy with established treatments. Histologic confirmation of the primary tumor by the Pathology Committee of the Gynecologic Oncology Group was required. All patients had measurable disease and had received 1 prior chemotherapeutic regimen. The evaluated agents included paclitaxel, pegylated liposomal doxorubicin, oxaliplatin, oral etoposide, dactinomycin, pyrazoloacridine, topotecan, irofulven (MGI-114), and flavopiridol. TFI was defined as the interval from the end of PCT until disease recurrence. The data from Gynecologic Oncology Group 129 was analyzed based on TFI instead of PFI-1 because data were only recorded for the date of completion of PCT without complete documentation of the starting date. However, both PFI-1 and TFI have been used interchangeably in prediction of treatment outcome of second-line chemotherapy in ovarian cancer.21 We further analyzed the data from Gynecologic Oncology Group 129, because this protocol had more detailed information on outcome collected, allowing us to assess the association of TFI with the immediate outcomes of RR, 6-month PFS (%), and PFS after second-line chemotherapy, in addition to the OS. Response rate included both complete and partial response.
Survival by PFI-1 or TFI group was estimated using Kaplan-Meier procedure,22 and Cox regression model was used to assess the association of PFI-1 or TFI with survival adjusted for covariates.23 For analysis, PFI-1 was categorized as >6 months versus ≤6 months, and TFI as >3 months versus ≤3 months based on their midpoints. The tumor response or PFS rate at 6 months by TFI group from Gynecologic Oncology Group 129 was compared using Pearson chi-square test.
A flow diagram outlining the time intervals and treatment characterizations can be referenced in Figure 1.
Part 1 of this analysis involved evaluable patients who participated in Gynecologic Oncology Group protocols 107, 122, 139, 163, and 177. A total of 586 patients with advanced or recurrent endometrial cancer who recurred or progressed after PCT on 1 of these 5 protocols and received second-line chemotherapy were included in this analysis. Demographic and treatment characteristics at primary treatment, as well as some clinical information at second-line treatment for this group, are outlined in Table 1. The median age was 63 years. The majority of patients were Caucasian. Sixty-four percent of patients received PCT for recurrent disease, as opposed to adjuvant therapy for advanced disease (36%); 51% of the cohort received prior radiation therapy. The most common cytotoxic regimen used was doxorubicin plus cisplatin (65%), and 24% had received paclitaxel. These baseline characteristics at primary treatment were evaluated in relation to survival after second-line chemotherapy. Race, performance status (PS), stage, tumor grade, and prior radiotherapy (RT) at the time of PCT that had been previously associated with treatment response and PFS after PCT13, 14 were also predictive of survival after disease recurrence (Table 2).
|Characteristic||No. of Patients (%)|
|At primary chemotherapy|
|GOG performance status|
|Stage of disease|
|Clear cell||27 (5)|
|3 or not graded||321 (55)|
|Prior surgery||463 (79)|
|Prior hormone||103 (18)|
|Prior RT||300 (51)|
|Doxorubicin (GOG107)||62 (11)|
|Doxorubicin and cisplatin (GOG 107, 122, 139, 163, 177)||382 (65)|
|Doxorubicin and paclitaxel (GOG 163)||86 (15)|
|Doxorubicin, cisplatin, and paclitaxel (GOG 177)||56 (10)|
|At second-line treatment|
|Other treatment||402 (69)|
|Race (black vs white)||1.43||1.11-1.84||.006|
|1 vs 0||1.31||1.10-1.57||.002|
|2 vs 0||1.68||1.19-2.36||.003|
|Stage (IV/recurrent vs III)||1.38||1.03-1.84||.031|
|2 vs 1||1.41||1.08-1.85||.012|
|3 vs 1||1.61||1.25-2.07||.0003|
|Prior RT (yes vs no)||1.28||1.06-1.54||.009|
The median time from primary treatment to disease relapse (PFI-1) was 6.7 months. Thirty-one percent of these recurrent patients received platinum-based chemotherapy for second-line treatment. When PFI-1 and type of second-line therapy, along with race, PS, stage, grade, and prior RT were included for analysis, PFI-1 became the most significant factor predictive of survival after recurrence; race, PS, stage, grade, and prior RT remained significant. Compared with patients with a PFI-1 ≤6 months, those with PFI-1 >6 months had a 30% reduction in the risk of death (HR, 0.70; 95% CI, 0.59-0.84 [P < .0001]). There was no evidence that the type of second-line therapy (platinum vs nonplatinum) was associated with survival (HR, 0.92; 95% CI, 0.77-1.11 [P = .392])(Table 3). Furthermore, when we restricted the analysis to patients who had primary treatment with platinum-based chemotherapy (n = 483), the results were essentially the same.
|Salvage treatment (platinum vs nonplatinum)||0.92||0.77-1.11||.392|
|PFI-1 (>6 vs ≤6 months)||0.70||0.59-0.84||<.0001|
Figure 2 demonstrates the survival since disease recurrence by PFI-1 and the type of second-line treatment. For patients with a PFI-1 >6 months, median OS was approximately 10 months, and for those with PFI-1 ≤6 months, median OS was 6 to 7 months regardless of type of secondary therapy. Furthermore, we investigated whether the prognostic value of PFI-1 was different among patients who were initially treated for advanced disease versus those who were treated because of disease recurrence. This analysis acknowledges the different inclusion criteria for those patients enrolled in Gynecologic Oncology Group 122 (residual disease <2 cm; no recurrent patients). Of the 586 patients in this analysis, 212 (36%) received PCT for advanced disease, and 127 (60%) of 212 of these patients were enrolled in Gynecologic Oncology Group 122. When we evaluated the effect of PFI-1 after PCT for advanced versus recurrent patients, the results were very consistent with median OS for advanced patients with PFI-1 >6 months of 10.9 months versus 9.9 months for recurrent patients. Similarly, advanced patients with PFI-1 ≤6 months had a median OS of 6.7 months versus 6.6 months for recurrent patients. These results demonstrated that the association of PFI-1 with OS after disease recurrence was consistent regardless of whether patients were initially treated for advanced or recurrent disease.
Data from Gynecologic Oncology Group 129 B, C, E, H, I, J, K, L, and M were reviewed to determine whether the TFI calculated from the end of first-line therapy to the date of entering Gynecologic Oncology Group 129 could be used to predict the treatment outcome after second-line therapy. Of 294 eligible patients who enrolled, 275 patients who had completed data were included for analysis. The basic demographic data for this cohort are outlined in Table 4. The majority of patients were Caucasian (82%). Eighty-nine percent were treated with a platinum-based regimen for first-line therapy. The median TFI for this cohort preceding treatment on a 129 protocol was 2.9 months.
|Characteristic||No. of Patients (%)|
|Age, median y (range)||66 (37-88)|
|Clear cell||11 (4)|
|Median TFI, mo||2.9|
The survival was calculated from date of entering Gynecologic Oncology Group 129 to death and was evaluated against the TFI. There is no significant evidence from these data that RR was associated with TFI (>3 months compared with ≤3 months, 9.6% vs 5.8%; P = .235) nor was PFS rate at 6 months (20.6% vs.17.2; P = .482) or median PFS (2.7 vs 2.1 months; P = .120). However, OS was significantly associated with the TFI (median, 10.2 vs 7.4 months; P = .014). This result was consistent when adjusted for age, PS, and grade, with an HR of 0.75 (95% CI, 0.57-0.97; P = .030) (Table 5). Figure 3 depicts the survival curve from time of initiation of the 129 series, stratified by TFI of >3 or ≤3 months, again demonstrating the association between longer TFI and improved OS.
|Outcome||TFI ≤3 Months (n=139)||TFI >3 Months (n=136)||P|
|Tumor response, %||5.8||9.6||.235|
|PFS at 6 months, %||17.3||20.6||.482|
|Median PFS, mo||2.1||2.7||.120|
|Median survival, mo||7.4||10.2||.014|
Cytotoxic chemotherapy is increasingly being incorporated into the management of advanced and recurrent endometrial cancer. On the basis of several phase 3 trials performed by the Gynecologic Oncology Group, combination regimens appear to confer superior outcomes as compared with single-agent regimens. Recently, the use of doxorubicin plus cisplatin on Day 1 followed by paclitaxel on Day 2 as compared with doxorubicin plus cisplatin has demonstrated improved OS as well as RR, making it the most active combination regimen tested to date.5 Despite this, in patients with advanced and recurrent disease, the complete RR ranging from 9% to 22%. Even in patients with minimal residual disease, such as those treated on Gynecologic Oncology Group protocols 122 and 184, the recurrence rate still approaches 50%.2, 24 As a result, a sizable population exists for whom active second-line therapy is needed. How to best treat this population is unclear.
Although a commonly used paradigm attempts to treat these patients with sequential salvage chemotherapeutic agents in the manner of ovarian cancer, the lack of active agents for endometrial cancer limits the efficacy of this approach. Given the poor outcome for these patients, this is a clear area of research emphasis on multiple fronts.
One approach would be to use the agents we already know to be active (doxorubicin, cisplatin, and paclitaxel) and attempt to discern which factors are predictive of response at the time of re-treatment. Our study attempted to address this question by evaluating the prognostic value of the PFI while adjusting for other known prognostic factors. Our results based on the Gynecologic Oncology Group 129 series (1 prior therapy) were generally consistent with those obtained from analysis of first-line studies (Gynecologic Oncology Group 107, 122, 139, 163, and 177). In the analysis of PCT protocols, a PFI-1 >6 months was associated with a 30% reduction in the risk of death after adjustment for age, race, performance status, stage, grade, and prior radiation. These results were also consistent whether the patient was treated for advanced stage or recurrent disease. In the analysis of second-line chemotherapy protocols (Gynecologic Oncology Group 129 series), a TFI >3 months was associated with a 25% reduction in the risk of death when adjusted for the same factors. The median PFI-1 of 6 months and TFI of 3 months overlap and are roughly the same time point, and we can say that our data suggest that the disease-free interval after primary therapy is predictive of prognosis after secondary chemotherapy for patients with advanced or recurrent disease. Unfortunately, unlike ovarian cancer, this time interval does not appear to aid in selection of secondary chemotherapy for recurrence. This variable is more likely a general prognostic factor, or may be indicative of pan-drug resistance/sensitivity, but not related to the tumor response to a specific drug for secondary chemotherapy.
A second approach is continued development of active new drugs. Combining biologic agents or adding them with active cytotoxic drugs may be a more successful strategy than using single agents in this population. Early reports from Gynecologic Oncology Group 229E that evaluated the use of single-agent bevacizumab in this population are promising, with a 6-month PFS of 39%.25 Bevacizumab was recently paired with the mammalian target of rapamycin inhibitor temsirolimus in Gynecologic Oncology Group 0229G; analysis of this study is currently underway, but may build on the successes of single-agent bevacizumab.
A third approach is to consider alternative clinical trial designs and study endpoints. Our study attempted to look at whether the TFI was predictive of 6-month PFS after second-line chemotherapy, and we were failed to identify a significant difference (17% for TFI ≤3 months vs 21% for TFI >3 months). Given an increased utilization of this endpoint in studies carried out in this population, further studies should be still considered. Although 6-month PFS is a current statistical endpoint in the Gynecologic Oncology Group 229 (biologic) series, it has not traditionally been used as an endpoint for 129 (cytotoxic) series. Interestingly, if one considers 6-month PFS as the endpoint of interest for these studies with a cutoff of >20% warranting further evaluation, then the following agents would have been advanced: paclitaxel (6-month PFS, 21%), Doxil (23%), topotecan (25%), oxaliplatin (27%), and irofulven (28%).6-8, 18, 19 This is compared with success based on RR, where only paclitaxel was approved for further study. In patients with terminal disease, deciding on an appropriate study outcome may change how we interpret success in these protocols.
In summary, we performed an ancillary data analysis on both primary and secondary treatment protocols for advanced/recurrent endometrial cancer to determine whether a time interval analogous to that used in ovarian cancer existed with which we could triage patients into prognostic groups. We did find that such an interval is prognostic; however, the clinical utility of this variable in selecting secondary treatment for recurrence is likely limited. Attempting to apply an ovarian cancer treatment paradigm to advanced/recurrent endometrial cancer is attractive, given the progress we have achieved in treatment of ovarian cancer. The barrier we face in translating ovarian cancer outcomes to endometrial cancer is the absence of an agent with extreme activity against endometrial cancer. With the introduction of platinum to the ovarian cancer treatment paradigm, RRs and PFS markedly improved.26 Although platinum agents, taxanes, and anthracyclines all appear to have activity, none to date have demonstrated the type of activity required to drastically change the duration of first PFS. In addition, the absence of additional active salvage agents limits the application of sequential salvage chemotherapy in this population, even if we were to prolong first PFS.
CONFLICT OF INTEREST DISCLOSURES
Supported by a Young Investigator's Grant awarded by the Gynecologic Oncology Group and National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office (CA 27469) and the Gynecologic Oncology Group Statistical Office (CA 37517). Dr. Thigpen has acted as a consultant for Amgen, Boehringer Ingleheim, Bristol-Myers Squibb, GlaxoSmithKline, Novartis, Lilly, Ortho-Biotech, Cell Therapeutics, Sanofi-Aventis, Celgene, Genentech, McNeill, EMD, Berlex, Bionumerik, Sunesis, Expression Genetics, Pfizer, Menarini, Astra Zeneca, and Oxigene and has been a member of the Speakers' Bureau for GlaxoSmithKline, Lilly, and Ortho-Biotech. He has also participated in the Physicians Education Resource.
- 23Regression models and life-tables. J R Stat Soc B. 1972; 34: 187-220.
- 25A phase II evaluation of bevacizumab in the treatment of recurrent or persistent endometrial cancer: a GOG study [abstract]. J Clin Oncol. 2009; 27( 15S pt I): 284S. Abstract 5531., , , et al.