A New Paradigm in Managing Advanced Ovarian Cancer: Differentiating Patients Requiring Neoadjuvant Treatment from Primary Cytoreduction

Our study aims to evaluate the comparability of primary debulking surgery (PDS) and neoadjuvant chemotherapy (NACT) patients. This single-center retrospective study includes all patients treated for advanced stages high-grade serous ovarian carcinomas (HGSOC) between 2007 and 2017. Preoperative characteristics and postoperative outcomes were compared after a propensity score matching analysis. Of the 221 patients included, 38% underwent PDS, and 62% received NACT. There was no age difference at diagnosis; however, CA125 levels, PCI score levels, and rates of stage IV were higher in the NACT group. There were no differences concerning the rate and the severity of complications (p = 0.29). The propensity score distribution showed a broad distinction between PDS patients and NACT patients with no significant overlap. Survival analyses demonstrate, after a median follow-up of 66.5 months, an overall survival (OS) of 105.9 and progression-free survival (PFS) of 29.2 months in the PDS group, compared to OS of 52.8 and PFS of 18.9 months in the NACT group. Advanced HGSOC is a heterogeneous population, in which inoperable patients should be differentiated from PDS patients based on many factors, primarily tumor burden.

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Combination of mitotane and locoregional treatments in low-volume metastatic adrenocortical carcinoma

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab449 ◽

2021 ◽

Author(s):

Alice Boileve ◽

Elise Mathy ◽

Charles Roux ◽

Matthieu Faron ◽

Julien Hadoux ◽

...

Keyword(s):

Adrenocortical Carcinoma ◽

Stage Iv ◽

Retrospective Chart Review ◽

Progression Free Survival ◽

Complete Response ◽

Tumor Burden ◽

Interquartile Range ◽

First Line ◽

Chemotherapy Administration ◽

Metastatic Sites

Abstract Purpose European and French guidelines for ENSAT stage IV low tumor burden or indolent adrenocortical carcinoma (ACC) recommend combination of mitotane and locoregional treatments (LRT) in first-line. Nevertheless, the benefit of LRT combination with mitotane has never been evaluated in this selected group of patients. Methods A retrospective chart review was performed from 2003-2018 of patients with stage IV ACC with ≤2 tumoral organs who received mitotane in our center. Primary endpoint was the delay between mitotane initiation and first systemic chemotherapy. Secondary endpoints were progression-free survival (PFS) and overall survival (OS) from mitotane initiation. Adjusted analyses were performed on the main prognostic factors. Results Out of 79 included patients, 48 (61%) patients were female and median age at stage IVA diagnosis was 49.8 years (interquartile-range:38.8-60.0). Metastatic sites were mainly lungs (76%) and liver (48%). Fifty-eight (73%) patients received LRT including adrenal bed radiotherapy (14 patients, 18%), surgery (37 patients, 47%) and/or interventional radiology n(35,44%). Median time between mitotane initiation and first chemotherapy administration was 9 months (Interquartile-range:4-18). Median PFS1 (first tumor-progression) was 6.0 months (CI95%:4.5-8.6). Median OS was 46 months (CI95%:41-68). PFS1, PFS2 and OS were statistically longer in the mitotane plus LRT group compared to the mitotane-only group (Hazard ratio (HR)=0.39 (CI95%:0.22-0.68), HR=0.35 (CI95%:0.20-0.63) and HR=0.27 (CI95%:0.14-0.50) respectively). Ten (13%) patients achieved complete response, all from mitotane plus LRT group. Conclusion Our results endorse European and French guidelines for stage IV ACC with ≤2 tumor-organs and favor the combination of mitotane and LRT as first-line treatment. For the first time, a significant number of complete responses were observed. Prospective studies are expected to confirm these findings.

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Comparison between Y90 Radioembolization Plus Sorafenib and Y90 Radioembolization alone in the Treatment of Hepatocellular Carcinoma: A Propensity Score Analysis

Cancers ◽

10.3390/cancers12040897 ◽

2020 ◽

Vol 12 (4) ◽

pp. 897

Author(s):

Antonio Facciorusso ◽

Irene Bargellini ◽

Marina Cela ◽

Ivan Cincione ◽

Rodolfo Sacco

Keyword(s):

Hepatocellular Carcinoma ◽

Propensity Score ◽

Liver Toxicity ◽

Propensity Score Analysis ◽

Objective Response ◽

Progression Free Survival ◽

Tumor Burden ◽

Y90 Radioembolization ◽

Group 2 ◽

Group 1

Background: Adjuvant sorafenib may enhance the efficacy of transarterial radioembolization with yttrium-90 in hepatocellular carcinoma patients. The aim of this study is to assess the efficacy and safety of radioembolization plus sorafenib in comparison to radioembolization alone. Methods: Out of 175 hepatocellular carcinoma (HCC) patients treated with radioembolization between 2011 and 2018, after propensity score matching, two groups were compared: a group of 45 patients that underwent radioembolization while being on sorafenib (Group 1) and a second group of 90 patients that underwent radioembolization alone (Group 2). Results: Baseline characteristics of the two groups were well balanced concerning liver function and tumor burden. No significant differences in survival outcomes were identified (median overall survival 10 vs. 10 months; p = 0.711), median progression-free survival 6 vs. 7 months (p = 0.992) in Group 1 and Group 2). The objective response rate in Group 1 vs. Group 2 was 45.5% vs. 42.8% (p = 1) according to mRECIST. No differences in toxicity nor in liver decompensation rates were registered. Conclusions: The association of sorafenib does not prolong survival nor delay progression in patients treated with radioembolization. Liver toxicity does not differ among the two therapeutic schemes.

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Final results of After-6 protocol 1: A phase III trial of observation versus 6 courses of paclitaxel (Pac) in advanced ovarian cancer patients in complete response (CR) after platinum-paclitaxel chemotherapy (CT)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.5505 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 5505-5505 ◽

Cited By ~ 7

Author(s):

P. F. Conte ◽

G. Favalli ◽

A. Gadducci ◽

D. Katsaros ◽

P. L. Benedetti Panici ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Survival Rates ◽

Advanced Ovarian Cancer ◽

Stage Iv ◽

Experimental Treatment ◽

Progression Free Survival ◽

Phase Iii ◽

First Line ◽

Absolute Increase

5505 Background: The majority of advanced ovarian cancer patients (pts) in CR after debulking surgery and Platinum/Paclitaxel will eventually relapse. Role of maintenance CT is still questionable even if a SWOG/GOG trial has shown an improved progression free survival (PFS) with 12 vs 3 cycles of maintenance Pac. In March 1999, the After 6 Italian Cooperative Group initiated a phase III study to determine if maintenance Pac could prolong PFS in pts with a clinical (cCR) or pathological CR (pCR) after first line CT Methods: Pts with advanced ovarian cancer in cCR or pCR after 6 cycles of Platinum/Paclitaxel, were randomised to observation or 6 cycles of Pac 175 mg/sqm iv q 3 wks. Primary end point: PFS; secondary end points: overall survival (OS) and toxicities. Planned sample size: 250 pts to detect a 15% absolute increase in 2-yr PFS. Results: From 03/99 to 07/06, 200 pts were randomised. Due to the low accrual rate, an unplanned interim analysis of futility according to the Bayesian approach was performed. Main patient characteristics: median age 58 yrs, median PS 0 (neurotoxicity ≥ G 2 was an exclusion criteria), stage IIb/IIc 15%, stage III 79%, stage IV 6%; 105 pts (52.5%) were in pCR. 14% of pts randomised to observation received Pac; 22% of pts randomised to Pac stopped treatment after 2–5 cycles (progression or death: 3 pts; toxicity: 9 pts; refusal: 7 pts; others: 3 pts). A G ≥ 2 neurotoxicity was reported in 25% of pts treated with Pac; other toxicities were mild. After a median follow up of 44 months, 94 pts (47%) have relapsed and 42 pts (21%) died. Median PFS were 34 and 34.5 months in observation and Pac arm respectively; 3-yr OS was 88% in observation and 78% in Pac arm. Irrespectively of treatment arm, median PFS was 34.4 months for pts with pCR and 24.5 months for those with cCR; 3-yr survival rates were 87% and 79% respectively (p=0.04). Conclusions: Six courses of maintenance Pac do not prolong PFS or OS in pts in CR after first line platinum/paclitaxel. Irrespectively of assigned treatment, the outcome of these pts is more favourable than previously reported and significantly better in the pCRs. Maintenance CT remains an experimental treatment that should be tested in pts at high risk of relapse. [Table: see text]

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Retrospective analysis of surgical outcomes and survival in women with advanced ovarian cancer undergoing interval debulking surgery

10.1055/s-0039-1685404 ◽

2016 ◽

Author(s):

Neha Kumar ◽

Amita Maheshwari ◽

Sudeep Gupta ◽

Jaya Ghosh ◽

Jyoti Bajpai ◽

...

Keyword(s):

Ovarian Cancer ◽

Advanced Ovarian Cancer ◽

Stage Iv ◽

Progression Free Survival ◽

Ca 125 ◽

Optimal Cytoreduction ◽

Stage Iiic ◽

Free Survival ◽

Peritoneal Cancer ◽

Interval Debulking Surgery

Introduction: Both primary (PDS) and interval debulking surgery (IDS) have reported similar progression free survival (PFS) and overall survival (OS) rates in various studies. Complete resection of all macroscopic disease is the strongest independent variable in predicting survival in both groups. Objective: To evaluate the demographics, surgical outcomes and survival in women with advanced ovarian cancer undergoing IDS. Methods: All women with Stage IIIC or Stage IV epithelial ovarian or primary peritoneal cancer, registered at our institution from January 2010 to December 2010, who were treated with NACT followed by IDS, were included in the study. Demographic data, CA-125 levels (baseline and presurgery), chemotherapy and surgical details were collected. Progression free survival (PFS) and overall survival (OS) were calculated and Cox regression and Kaplan-Meier survival analysis were used to evaluate factors associated with survival. Results: One hundred fifty women with Stage IIIC or Stage IV epithelial ovarian or primary peritoneal cancer were included in the analysis. The mean age was 51.08 years (27 to 73 years) and 97.3% had serous histology. Eighty percent (n = 120) had Stage IIIC and 20% (n = 30) had Stage IV disease. Ninety five percent women received Carboplatin and Paclitaxel or single agent Carboplatin as NACT and the median number of NACT cycles was 3. The median baseline CA-125 was 1649.3 U/ml (Range 16.4–235,100 U/ml) and the median CA-125 post NACT was 42.75 U/ml (Range 4.4–5151 U/ml). Seventy four percent women (n = 111) underwent an optimal cytoreduction – 62.7% (n = 94) had R0 and 11.3% (n = 17) had R1 resection. Twenty six percent women (n = 39) had R2 resection. The median CA-125 post NACT was 27.3 U/ml, 36 U/ml and 99 U/ml in women with R0, R1 and R2 resection respectively and the difference was statistically significant (p < 0.0005). The CA125 response was respectively, 97.6%, 95.7% and 93.8% in R0, R1 and R2 resection (p < 0.0005). The median follow up was 42.48 months (Range 1.48–70.93 months). The median PFS was 12.06 months (95% CI 10.02-14.1) – 12.98 months (95% CI 9.7–16.2) in R0, 9.56 months (95% CI 1.7–17.4) in R1 and 6.64 months (95% CI 4.9–8.3) in women with R2 resection (p = 0.158). The median OS was 38.9 months (95% CI 31.7–46.1) – 43.3 months (95% CI 33–53.5) in R0, 46.1 months (95% CI 26.6–65.5) in R1 and 28 months (95% CI 25–30.9) in R2 resection (p = 0.121). The median PFS and OS in women undergoing optimal cytoreduction (R0 and R1) was 12.98 months (95% CI 9.86–16.1) and 43.7 months (95% CI 34.7–52.7) respectively as compared to 6.64 months (95% CI 4.95–8.32) and 28 months (95% CI 25–30.9) respectively in women with R2 resection (PFS p = 0.064, OS p = 0.04). Multivariate analysis discussing the factors affecting the probability of optimal cytoreduction and the survival will be discussed. Conclusion: In women with advanced ovarian cancer undergoing NACT followed by IDS, a high rate of optimal cytoreduction is achieved. Residual disease is a primary factor affecting the survival of these women.

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Carcinosarcomas of Ovary/Fallopian Tube: A Rare Entity

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa161.056 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S28-S29

Author(s):

D M Vo ◽

K Verma ◽

P Khullar ◽

W Vintzileos ◽

E Jimenez

Keyword(s):

Fallopian Tube ◽

Tp53 Mutation ◽

Stage Iv ◽

Progression Free Survival ◽

High Grade ◽

Sarcomatous Component ◽

Ovarian Carcinomas ◽

Epithelial Component ◽

Lost To Follow Up

Abstract Introduction/Objective Adnexal carcinosarcomas (MMMTs) are rare tumors (1–4% ovarian carcinomas) with worse prognosis than high grade serous carcinomas (HGS) at similar stage. They typically present at age 64–66, often with peritoneal involvement. They are biphasic tumors with stem cells undergoing divergent epithelial and sarcomatous differentiation. The epithelial component is usually HGS and drives progression of the tumor. The mesenchymal component can be homologous with high-grade spindled cells or heterologous with malignant cartilage, bone, muscle or fat. Metastases are mostly epithelial; metastatic sarcomatous components are unusual. We reviewed our single- institutional experience of adnexal MMMTs. Methods We reviewed our pathology database (2001–2019) to find all cases of adnexal MMMTs. We reviewed their histological features, histology of metastases and clinical outcomes. Results Our series consisted of 12 cases. Patients aged 41–82 years. The primary tumor sites were ovary (6 cases, 50%), fallopian tube (4, 33%), 1 each (8%) in paratubal region and infundibular ligament. Fallopian tube was involved in 8/12 cases (4 cases as primary MMMT, 4 cases with STIC or HGS). Epithelial component was serous (75%), endometrioid (17%) and mucinous (8%). Sarcomatous component was homologous in 5 cases (41%), heterologous in 7 cases: cartilage (33%), cartilage/muscle (8%), muscle (8%), cartilage/muscle/fat (8%). 3 cases were FIGO stage I, 9 had peritoneal metastases (8 stage III, 1 stage IV). Six cases had metastatic HGS; 3 had metastatic HGS with sarcomatous component, 2 with heterologous elements. Aberrant p53 pattern was seen in 7/12 and TP53 mutation was noted in 6/12. Ten patients received cytoreductive surgery and chemotherapy. 7 patients are alive with progression free survival ranging 6–59 months, 2 survived for 25 and 29 months, 3 are lost to follow-up. Conclusion Metastatic sarcomatous heterologous elements are rare in uterine carcinosarcomas and may suggest adnexal origin. They may correlate with worse outcome; in our series, 1/2 died after 29 months, the other was lost to follow-up. Fallopian tube involvement (75% of our cases) is of significance as identical TP53 mutation has been identified in a case report of ovarian carcinosarcoma with fallopian tube STIC. Also, our 2 cases of infundibular ligament and paratubal region may indicate seeding from fallopian tube. Further studies are needed to confirm the correlation.

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Randomized, open-label, phase II trial of gemcitabine with or without bavituximab in patients with nonresectable stage IV pancreatic adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.4054 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 4054-4054 ◽

Cited By ~ 2

Author(s):

Shuchi Sumant Pandya ◽

Lucas Wong ◽

Andrea J. Bullock ◽

Stephen A. Grabelsky ◽

Merrill Kingman Shum ◽

...

Keyword(s):

Treatment Options ◽

Stage Iv ◽

Progression Free Survival ◽

Hepatic Function ◽

Tumor Burden ◽

Moderate Activity ◽

Open Label ◽

Eligibility Criteria ◽

First Line Therapy ◽

Significant Difference

4054 Background: Despite advances in the treatment of metastatic pancreatic cancer (PC), there is critical need to develop novel therapies.Median survival with combination chemotherapy is limited to less than one year and only the optimally conditioned patients can tolerate these therapies. Bavituximab (B) is a monoclonal antibody (mAB) directed againstphosphatidylserine (PS) that causes vascular shutdown and reactivation of the innate and adaptive immunity in animal models. Preclinical data in mouse PC models indicate that gemcitabine (G) increases PS exposure and the addition of a mAb targeting PS reduces tumor burden, visible liver metastases, microvessel density, and increases tumor macrophage infiltration compared to G alone (Beck et al. 2006). The purpose of this trial is to evaluate and compare the efficacy and safety of the combination of G+B vs. G alone as first line therapy in pts. with nonresectable Stage IV PC. Methods: Seventy patients were randomized (1:1) to receive G 1000 mg/m2 on days 1, 8, and 15 every 28Edays with or without weekly B 3mg/kg IV until disease progression or unacceptable toxicities. Key eligibility criteria were Stage IV PC, ECOG ≤2, measurable disease, age≥18 years, total bilirubin ≤1.5xULN, and adequate renal, hematologic, and hepatic function. The primary efficacy endpoint was overall survival (OS) and secondary endpoints included overall response rate (ORR) and progression free survival (PFS). Results: Of the 70 (G/G+B 34/36) patients randomized, 67 (G/G+B 33/34) received study treatment and 63 (G/G+B 31/32) were evaluable. No significant difference was seen in age, gender, race or ECOG. At analysis 87% deaths had been reported in G and 72% in G+B group. Median OS estimate is 5.2 months for G and 5.6 months for G+B. No difference between groups was observed in PFS (median 3.9 months for G and 3.7 months for G+B). ORR was 13% for G and 28% for G+B. Most AEs were grade 1-2 and typical of exposure to G. Conclusions: In this patient population with extensive disease burdens and limited treatment options, G+B was well tolerated and demonstrated moderate activity in tumor response and survival. Clinical trial information: NCT01272791.

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Clinicopathologic characteristics of endometrial carcinoma metastatic to the ovary compared to endometrial carcinoma with synchronous ovarian carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e17105 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e17105-e17105

Author(s):

Natalia Rodriguez Gomez Hidalgo ◽

Robert A. Soslow ◽

Britta Weigelt ◽

Vasileios Sioulas ◽

Alessia Aloisi ◽

...

Keyword(s):

Endometrial Carcinoma ◽

Statistical Tests ◽

Stage Iv ◽

Progression Free Survival ◽

Ovarian Carcinomas ◽

Clinicopathologic Characteristics ◽

Entire Cohort ◽

Primary Surgery ◽

Pathology Reports

e17105 Background: According to recent reports, sporadic synchronous endometrial and ovarian cancers (SEOCs) of endometrioid histology may be clonally related. We sought to characterize the clinicopathologic characteristics and outcomes of patients with SEOC compared to those with endometrial carcinoma felt to have metastasis to the ovaries. Methods: All patients with endometrial cancer who underwent primary surgery at our institution from 06/1993- 09/2014 were identified. We included cases with carcinoma in the endometrium and ovary. Pathology reports were reviewed to determine the pathologist’s assessment of whether the ovarian carcinomas were likely synchronous or metastatic. Patients with stage IV endometrial carcinoma, irrespective of presence of ovarian disease, were excluded. Appropriate statistical tests were performed. Results: We identified 76 eligible cases; 19 were deemed SEOCs and 57 endometrial carcinoma with ovarian metastasis (ECOM). Median age was 52 years (range, 32-71) and 63 years (range, 43-89), respectively (p = 0.4). Non-endometrioid histology was observed in 21% of SEOCs compared with 58% of ECOMs (p = 0.006). There was no myoinvasion in 32% of SEOCs compared with 9% of ECOMs (p = 0.01). Endometriosis was noted in 58% of SEOCs compared with 4% of ECOMs (p < 0.0001). The median follow-up time was 44.2 months (range, 0.4-201.4) for the entire cohort. The 4-year progression-free survival (PFS) rates were 82% (SE+/-9.5) for SEOCs and 51.6% (SE+/- 7) for ECOMs (p = 0.06). The 4-year overall survival (OS) rates were 94.7% (SE+/-5.1) for SEOCs and 69.8% (SE+/-6.2) for ECOMs (p = 0.046). The 4-year PFS rates for cases of endometrioid histology alone were 84% (SE+/-10.6) for SEOCs and 77.8% (SE+/-8.87) for ECOMs (p = 0.97). The 4-year OS rates for cases of endometrioid histology alone were 93.3% (SE+/-8.4) and 81.9% (SE+/-8.2), respectively (p = 0.3). Conclusions: SEOC was associated with more favorable endometrial factors and with the presence of endometriosis, consistent with the notion that these are likely dissemination by retrograde flux. SEOC was associated with better survival outcomes but not when analyzing endometrioid histology alone.

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Immune Monitoring in Melanoma and Urothelial Cancer Patients Treated with Anti-PD-1 Immunotherapy and SBRT Discloses Tumor Specific Immune Signatures

Cancers ◽

10.3390/cancers13112630 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2630

Author(s):

Annabel Meireson ◽

Simon J. Tavernier ◽

Sofie Van Gassen ◽

Nora Sundahl ◽

Annelies Demeyer ◽

...

Keyword(s):

T Cells ◽

Clinical Outcome ◽

Cd8 T Cells ◽

Immune Cell ◽

Stage Iv ◽

Progression Free Survival ◽

Fixed Time ◽

Immune Monitoring ◽

Tumor Burden ◽

Durable Response

(1) Background: Blockade of the PD-1/PD-L1 pathway has revolutionized the oncology field in the last decade. However, the proportion of patients experiencing a durable response is still limited. In the current study, we performed an extensive immune monitoring in patients with stage III/IV melanoma and stage IV UC who received anti-PD-1 immunotherapy with SBRT. (2) Methods: In total 145 blood samples from 38 patients, collected at fixed time points before and during treatment, were phenotyped via high-parameter flow cytometry, luminex assay and UPLC-MS/MS. (3) Results: Baseline systemic immunity in melanoma and UC patients was different with a more prominent myeloid compartment and a higher neutrophil to lymphocyte ratio in UC. Proliferation (Ki67+) of CD8+ T-cells and of the PD-1+/PD-L1+ CD8+ subset at baseline correlated with progression free survival in melanoma. In contrast a higher frequency of PD-1/PD-L1 expressing non-proliferating (Ki67−) CD8+ and CD4+ T-cells before treatment was associated with worse outcome in melanoma. In UC, the expansion of Ki67+ CD8+ T-cells and of the PD-L1+ subset relative to tumor burden correlated with clinical outcome. (4) Conclusion: This study reveals a clearly different immune landscape in melanoma and UC at baseline, which may impact immunotherapy response. Signatures of proliferation in the CD8+ T-cell compartment prior to and early after anti-PD-1 initiation were positively correlated with clinical outcome in both cohorts. PD-1/PD-L1 expression on circulating immune cell subsets seems of clinical relevance in the melanoma cohort.

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Topotecan Compared With No Therapy After Response to Surgery and Carboplatin/Paclitaxel in Patients With Ovarian Cancer: Multicenter Italian Trials in Ovarian Cancer (MITO-1) Randomized Study

Journal of Clinical Oncology ◽

10.1200/jco.2004.09.088 ◽

2004 ◽

Vol 22 (13) ◽

pp. 2635-2642 ◽

Cited By ~ 117

Author(s):

Sabino De Placido ◽

Giovanni Scambia ◽

Giovanni Di Vagno ◽

Emanuele Naglieri ◽

Alessandra Vernaglia Lombardi ◽

...

Keyword(s):

Ovarian Cancer ◽

Residual Disease ◽

Randomized Study ◽

Advanced Ovarian Cancer ◽

Stage Iv ◽

Progression Free Survival ◽

Phase Iii ◽

Rank Test ◽

Significant Difference ◽

Grade 3

Purpose Topotecan is an active second-line treatment for advanced ovarian cancer. Its efficacy as consolidation treatment after first-line standard chemotherapy is unknown. Patients and Methods To investigate whether topotecan (1.5 mg/m2 on days 1 through 5, four cycles, every 3 weeks) prolonged progression-free survival (PFS) for patients responding to standard carboplatin (area under the curve 5) and paclitaxel (175 mg/m2 administered as a 3-hour infusion in six cycles; CP), a multicenter phase III study was performed with an 80% power to detect a 50% prolongation of median PFS. Patients were registered at diagnosis and randomized after the end of CP. Results Two hundred seventy-three patients were randomly assigned (topotecan, n = 137; observation, n = 136), with a median age of 56 years. Stage at diagnosis was advanced in three fourths of patients (stage III in 65% of patients; stage IV in 10%); after primary surgery, 46% had no residual disease and 20% were optimally debulked. After CP, 87% reached a clinical complete response, and 13% achieved a partial response. Neutropenia (grade 3/4 in 58% of the patients) and thrombocytopenia (grade 3 in 21%; grade 4 in 3%) were the most frequent toxicities attributed to topotecan. There was no statistically significant difference in PFS between the arms (P = .83; log-rank test): median PFS was 18.2 months in the topotecan arm and 28.4 in the control arm. Hazard ratio of progression for patients receiving topotecan was 1.18 (95% CI, 0.86 to 1.63) after adjustment for residual disease, interval debulking surgery, and response to CP. Conclusion The present analysis indicates that consolidation with topotecan does not improve PFS for patients with advanced ovarian cancer who respond to initial chemotherapy with carboplatin and paclitaxel.

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Maintenance Rituximab after CVP Results in Superior Clinical Outcome in Advanced Follicular Lymphoma (FL): Results of the E1496 Phase III Trial from the Eastern Cooperative Oncology Group and the Cancer and Leukemia Group B.

Blood ◽

10.1182/blood.v106.11.349.349 ◽

2005 ◽

Vol 106 (11) ◽

pp. 349-349 ◽

Cited By ~ 55

Author(s):

Howard S. Hochster ◽

Edie Weller ◽

Randy D. Gascoyne ◽

Teresa S. Ryan ◽

Thomas M. Habermann ◽

...

Keyword(s):

Follicular Lymphoma ◽

Survival Benefit ◽

Residual Disease ◽

Eastern Cooperative Oncology Group ◽

Prognostic Index ◽

Stage Iv ◽

Progression Free Survival ◽

Tumor Burden ◽

Phase Iii ◽

Phase Iii Trial

Abstract E1496 is a phase III trial designed to evaluate the ability of 2 years (yr) of maintenance rituximab (MR) to prolong progression-free survival (PFS) after CVP (cyclophosphamide 1 G/m2 day [d] 1, vincristine 1.4 mg/m2 [max = 2 mg] d 1, prednisone 100 mg/m2 d 1–5) chemotherapy in stage III–IV follicular grade 1 and 2 and small lymphocytic lymphoma. After CVP treatment to maximum response, (6–8 cycles), stable and responding patients (pt) were randomized to MR (375 mg/m2 weekly x 4) every 6 months x 4 or observation (OBS). Stratification factors included histology, response and residual disease after CVP. With 3-yr median follow-up, survivals (from time of randomization, one-sided logrank p values) for all pt (n=304) favored MR for PFS (p = 3 x 10–8; hazard rate {HR} = 0.38 [0.28;0.54, 95% confidence intervals]) and OS (p = 0.09; HR = 0.66 [0.36–1.22]). Because the large majority of pt have FL and because rituximab efficacy is notably greater in FL, we focused in this report on the 237 FL pt. Median age was 58 yr, 65% were stage IV, 64% had marrow disease, 64% had high tumor burden and 37% had high-risk disease by the follicular lymphoma prognostic index. PFS after randomization was significantly longer for MR vs OBS (p = 3 x 10-7; HR = 0.39 [0.27;0.57]). The estimated PFS at 4 yr (~4.5 yr after start of treatment) was 56% for MR vs 33% for OBS. Differences in PFS were significant within the predefined strata and the differences were most significant in favor of MR for pt with high initial tumor burden and minimal residual disease after CVP. Overall survival was superior for MR (p = 0.03; HR = 0.51 [0.25;1.04]. Estimated OS at 4 yr (~4.5 years after start of treatment) was 88% for MR vs 72% for OBS. Of 33 deaths, 21 occurred on the OBS arm. These data demonstrate that maintenance rituximab not only significantly delays disease progression in FL compared with OBS but that a substantial proportion of patients treated with MR remain disease-free at 4 years after the completion of CVP. These are the first data to strongly suggest a survival benefit with a therapy that includes rituximab and CVP and the first to strongly suggest a survival benefit with maintenance rituximab in FL.

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