Tisotumab vedotin (TV) is an investigational antibody-drug conjugate composed of a tissue factor-directed human monoclonal antibody covalently linked to cytotoxic MMAE. In the US, TV monotherapy received accelerated approval for the treatment of adult pts with recurrent or metastatic cervical cancer (r/mCC) with disease progression on or after chemotherapy. Here, innovaTV 301 (NCT04697628) study results of TV vs investigator’s choice of chemotherapy in pts with r/mCC following 1L therapy are presented.

Background The endometrial cancer molecular classification has been integrated into the 2020 World Health Organization (WHO) diagnostic classification and European treatment guidelines, and provides direction towards more effective and less toxic adjuvant treatment strategies for women with endometrial cancer. Primary Objective(s) The RAINBO program of clinical trials will investigate four molecular class-directed adjuvant treatment strategies following surgical resection to either increase cure rates through the addition of novel targeted therapies or safely reduce toxicity and improve quality of life through treatment de-escalation. Study Hypothesis Molecular-directed adjuvant treatment strategies will improve clinical outcomes and reduce toxicity of unwarranted therapies in women with endometrial cancer. The overarching and translational research RAINBO program will advance knowledge of predictive and prognostic (bio)markers that will improve prognostication and treatment allocation. Trial Design The RAINBO program is a platform of four international clinical trials and an overarching research program. The randomized phase III p53abn-RED trial for women with invasive stage I–III p53abn endometrial cancer compares adjuvant chemoradiation followed by olaparib for 2 years with adjuvant chemoradiation alone. The randomized phase III MMRd-GREEN trial for women with stage II (with lymphovascular space invasion (LVSI)) or stage III mismatch repair-deficient (MMRd) endometrial cancer compares adjuvant radiotherapy with concurrent and adjuvant durvalumab for 1 year to radiotherapy alone. The randomized phase III NSMP-ORANGE trial is a treatment de-escalation trial for women with estrogen receptor positive stage II (with LVSI) or stage III no specific molecular profile (NSMP) endometrial cancer comparing radiotherapy followed by progestin for 2 years to adjuvant chemoradiation. The POLEmut-BLUE trial is a phase II trial in which the safety of de-escalation of adjuvant therapy is investigated for women with stage I–III POLEmut endometrial cancer: no adjuvant therapy for lower-risk disease and no adjuvant therapy or radiotherapy alone for higher-risk disease. The overarching RAINBO program will combine data and tumor material of all participants to perform translational research and evaluate molecular class-based adjuvant therapy in terms of efficacy, toxicity, quality of life, and cost-utility. Major Inclusion/Exclusion Criteria Inclusion criteria include a histologically confirmed diagnosis of endometrial cancer treated by hysterectomy and bilateral salpingo-oophorectomy with or without lymphadenectomy or sentinel lymph node biopsy, with no macroscopic residual disease after surgery and no distant metastases, and molecular classification according to the WHO 2020 algorithm. Primary Endpoint(s) Recurrence-free survival at 3 years in the p53abn-RED, MMRd-GREEN, and NSMP-ORANGE trials and pelvic recurrence at 3 years in the POLEmut-BLUE trial. Sample Size The p53abn-RED trial will include 554 patients, the MMRd-GREEN trial 316, the NSMP-ORANGE trial 600, and the POLEmut-BLUE trial 145 (120 for lower-risk disease and approximately 25 for higher-risk disease). The overarching research program will pool the four sub-trials resulting in a total sample size of around 1600. Estimated Dates for Completing Accrual and Presenting Results The four clinical trials will have different completion dates; main results are expected from 2028. Trial Registration Number The RAINBO program is registered at clinicaltrials.gov (NCT05255653).

BACKGROUND:Patients with advanced endometrial cancer have a poor prognosis, and treatment options are limited. The investigator-initiated, multicenter, phase II DOMEC trial (NCT03951415) is the first trial to report data on efficacy and safety of combined treatment with PD-L1 and PARP inhibition for advanced endometrial cancer.PATIENTS AND METHODS:Patients with metastatic or recurrent endometrial cancer were enrolled. Patients received durvalumab 1500 mg intravenously q4w and olaparib 300 mg 2dd until disease progression, unacceptable toxicity, or patient withdrawal. Patients with at least 4 weeks of treatment were evaluable for analysis. The primary endpoint was progression-free survival at 6 months. Evidence for efficacy was defined as progression-free survival at 6 months in ≥50% of patients. Secondary endpoints included safety, objective response and overall survival.RESULTS:From July 2019, through November 2020, 55 patients were enrolled. At data cut-off (September 2021), 4 of the 50 evaluable patients were still on treatment. Seventeen patients (34%) were progression-free at 6 months. Objective response rate was 16% (95% CI, 8.3 to 28.5) with 1 complete and 7 partial responses. With a median follow-up of 17.6 months, median progression-free survival was 3.4 months (95% CI, 2.8 to 6.2) and median overall survival was 8.0 months (95% CI, 7.5 to 14.3). Grade 3 treatment-related adverse events occurred in 8 patients (16%), predominantly anemia. There were no grade 4 or 5 treatment-related adverse events.CONCLUSION:The combination of durvalumab and olaparib was well tolerated, but did not meet the prespecified 50% 6-month progression-free survival in this heterogeneous patient population with advanced endometrial cancer.

TV demonstrated durable activity (objective response rate [ORR]=24%; median duration of response [mDOR]=8.3 mo) with manageable safety in previously treated r/mCC (Lancet Oncol. 2021; 22:609-619). Here we report results for the 1L TV + carbo and 2L/3L TV + pembro cohorts of the 2-part, multi-cohort phase Ib/II trial ENGOT-cx8/GOG-3024/innovaTV 205 clinical trial in r/mCC. In the 1L TV + carbo cohort, pts with no prior systemic therapy (excluding chemoradiation) for r/mCC received TV 2.0 mg/kg + carbo AUC 5 IV every 3 weeks (Q3W). In the 2L/3L TV + pembro cohort, pts with r/mCC, with disease progression on/after 1–2 prior systemic therapies, received TV 2.0 mg/kg + pembro 200 mg IV Q3W. The primary endpoint was ORR per RECIST v1.1. There were 33 pts treated with 1L TV + carbo (median 5 cycles). Confirmed ORR was 55% (Table). All treated pts had adverse events (AEs) with 76% reporting grade (gr) ≥3 AEs regardless of causality. Prespecified AEs of interest (gr 1-2/ gr ≥3) included ocular (55%/3%), peripheral neuropathy (27%/12%) and bleeding events (48%/6%). There were 35 pts treated with 2L/3L TV + pembro (median 6 cycles), with most having received 1 prior systemic treatment for r/mCC (57%) and prior bevacizumab (57%). Confirmed ORR was 35% (Table). All treated pts had AEs with 74% reporting gr ≥3 AEs regardless of causality. AEs of interest included (gr 1-2/ gr ≥3) ocular (51%/3%), peripheral neuropathy (37%/3%) and bleeding events (54%/9%). There were no treatment-related deaths in either cohort. Both 1L TV + carbo and 2L/3L TV + pembro had encouraging antitumor activity with acceptable safety profiles in pts with r/mCC.Table: 723MOSummary of efficacyParameters1L TV + Carbo (N = 33) Median FU: 4.8 months2L/3L TV + Pembro (N = 34)a Median FU: 10.2 monthsObjective response rate, n (%) [95% CI]Complete response, n (%)Partial response, n (%)18 (55) [36–72]2 (6)16 (48)12 (35) [20–54]2 (6)10 (29)Median duration of response, months (range)5.6 (2.7-NE)NEMedian time to response, months (range)1.4 (1.1–4.4)1.4 (1.3–5.8)Median PFS, months (range)6.9 (3.9–NE)5.6 (2.7–9.6)NE, not estimable. a1 pt was excluded from the full analysis set as they didn’t have any target or non-target lesions at baseline. Response ongoing in 13/18 pts with 1L TV + carbo and 8/12 pts with 2L/3L TV + pembro. Open table in a new tab

Anti-PD-1/L1 therapy alone has limited activity in ovarian cancer. We hypothesised that blockade of VEGF and prostaglandin E2 (PGE2) can reverse the endothelial barrier allowing T cell infiltration and subsequent T cell activation by PD-L1 blockade. This is the first trial combining an anti-PD-L1 antibody, atezolizumab (ATE), with bevacizumab (BEV) and the irreversible COX1/2 inhibitor acetylsalicylic acid (ASA).

BACKGROUNDCombined administration of intravenous (iv) and intraperitoneal (ip) (iv/ip) chemotherapy is an effective adjuvant treatment option after primary debulking surgery (PDS) for advanced ovarian cancer (OC). Increased toxicityand patient burden limit its use in daily practice.OBJECTIVETo assess toxicity and survival outcomes of iv/ip chemotherapy in daily practice in the Netherlands.METHODSThis retrospective cohort study included 81 women who underwent at least an optimal PDS for FIGO stage III OC followed by iv/ip chemotherapy according to the Armstrong regimen, in four hospitals in the Netherlands between January 2007 and May 2016. We collected information on surgical procedure, abdominal port implantation, toxicity, and recurrence-free and overall survival.RESULTSAll participants underwent PDS, of whom 60 (74%) had their ip catheter implanted during PDS. Most frequently reported all grade toxicity was haematological n = 44 (54%). Forty-four patients (54%) completed all six cycles of iv/ip chemotherapy. The most frequent causes of discontinuation of iv/ip administration were renal dysfunction (12/37 = 32%) and catheter problems (7/37 = 19%). Median recurrence-free survival and overall survival were 24 months (range 0 - 108) and 80 months (range 4-115), respectively. Surgical outcome, completion of more than three courses of treatment and intra-abdominal localisation of recurrent disease were associated with better survival outcomes.CONCLUSIONIn daily practice, 54% of patients with advanced OC could complete all scheduled cycles of iv/ ip chemotherapy with acceptable morbidity and toxicity, leading to outcomes comparable with the results of published trials on iv/ip chemotherapy.

e17023 Background: Standard treatment of locally advanced cervical carcinoma consists of concurrent radiotherapy (including brachytherapy) and chemotherapy (weekly cisplatin 40 mg/m2), or chemoradiotherapy (CRT). Locoregional hyperthermia (HT) improves results of both radiotherapy and chemotherapy. After feasibility was demonstrated, an international multicenter randomized study of CRT ± hyperthermia was conducted. Methods: Patients with histologically confirmed advanced cervical cancer were randomized to CRT or CRT - HT. Weekly HT was applied concurrent with cisplatin. Primary endpoints were progression-free and overall survival. A total of 400 patients was needed to demonstrate a 15% PFS and OS advantage for triple therapy over chemoradiation, but the study was closed in 2010 because of insufficient patient accrual. We present the analysis of 99 randomized patients that were evaluable. Results: Between 2003 and 2010, 99 eligible Dutch, Norwegian and German patients were randomized to CRT (n = 50) or CRT-HT (n = 49). Patient characteristics (age, ECOG, FIGO) were well balanced between both groups and not statistically different. Patients were generally able to complete the protocol treatment of chemoradiotherapy. The median number of cisplatin courses was 6 in both groups, and in the triple group a median number of 5 treatments of hyperthermia were delivered. No unexpected toxicity occurred in either group. Complete responses were seen in 86% (42/49) of the patients in the CRT-HT group versus 76% (38/50) for CRT alone (p = 0.54). Five-year DFS (61.0 vs 58.7%) and 5-year OS (66.0 vs 70.7%) (p = 0.65, and p = 0.80) were not statistically different between both groups. Conclusions: In this underpowered study, no statistically significant improvement in treatment outcome by addition of hyperthermia to chemoradiotherapy could be demonstrated. Clinical trial information: NCT00085631.

HGUS accounts for 6% of all uterine sarcomas and has a very poor prognosis. Most patients (pts) die of recurrent disease within 1 year of diagnosis. Treatment recommendations for advanced stage include chemotherapy with anthracyclines +/- ifosfamide, although data for the efficacy of these agents in this histologic subtype are very limited. Recently vascular invasion reported to be a driver of the progression for such sarcoma subtype suggesting anti-angiogenics and so cabozantinib (VEGFR2/c-MET inhibitor) potentially active for HGUS. Trial design: This randomized phase II double-blinded trial aims to measure the role of maintenance therapy with cabozantinib in HGUS after stabilization (SD) or response (Complete Response (CR) + Partial Response (PR)) to doxorubicin-based chemotherapy following surgery or in metastatic 1st line treatment. The main objective of the trial is to assess the efficacy of maintenance treatment with cabozantinib compared with placebo. Approximately 54 pts will be randomized, after central pathological review, to cabozantinib 60 mg once daily or placebo for up to 24 months, to detect an improvement in progression free survival (PFS) rate at 4 months from 50% to 80% with a one-sided 15% significance level. Pts randomized to the placebo arm may cross-over to cabozantinib at the time of progression. This trial is a cooperation between European Organisation for Research and Treatment of Cancer (EORTC), Cancer Research UK (CRUK) and National Cancer Institute (NCI, US) and is part of the International Rare Cancers Initiative (IRCI). Primary objective: PFS rate at 4 months according to RECIST 1.1 Secondary objectives: PFS, Overall Survival, Safety, Response Rate and duration of response Study status: The first pts from EORTC (6 participating countries) was randomized in Feb 2015. As of 6 May 2016, 15 and 5 pts have been registered and randomized after central pathology confirmation of HGUS, respectively. CRUK has started recruitment in May 2016 and NRG Oncology in US is expected to start in October 2016. Clinical trial identification: NCT number: NCT01979393; EudraCT: 2013-000762-11 Legal entity responsible for the study: European Organisation for Research and Treatment of Cancer (EORTC) European Organisation for Research and Treatment of Cancer (EORTC)

There is a pressing need for second-line systemic treatment for metastatic, recurrent and/or locally advanced endometrial cancer (AEC) after hormonal therapy or chemotherapy. We studied the effect of the selective multi-targeted receptor tyrosine kinase inhibitor pazopanib on progression free survival (PFS) at three months for patients with AEC. In this prospective phase II open label study, patients were recruited from six oncology departments in the Netherlands. Eligible patients had histologically or cytologically confirmed AEC, documented progressive disease and a WHO performance status of ≤ 2. All participants received treatment with pazopanib 800 mg once daily until progression, unacceptable toxicity or patient refusal. Dose reductions for toxicity were allowed. Patients were evaluable for the primary endpoint of PFS at three months if they had received pazopanib for at least four weeks. All participants were analysed for toxicity and overall survival (OS). The study was powered to demonstrate 50% PFS at 3 months (vs <30% based on previously reported studies) with &agr; = 0.05 and &bgr; = 80%. Between January 2011 and February 2016, 60 eligible patients were included. Median age was 68 years (range 53-85). Previous treatment included pelvic radiotherapy (58%), chemotherapy (90%) and hormonal therapy (43%). Forty-five out of sixty patients were treated for at least four weeks, and were thus evaluable for the primary endpoint. Twenty-six of the evaluable patients (58%) had no progression at three months, with median PFS and OS of 5.3 and 9.5 months, respectively. The most common severe adverse events were gastrointestinal toxicity in 21% of 60 participants, including 2 patients with a gut perforation, one fatal gastrointestinal hemorrhage, one enterocutaneous fistula and one fatal enterovaginal fistula. Peritoneal disease existed in 80% of patients with severe gastrointestinal toxicity. A definite correlation with previous radiotherapy could not be established. Pazopanib showed encouraging 3 months PFS in AEC. There may be a correlation between previous treatments and/or disease site with rare but severe gastrointestinal toxicity that has yet to be elucidated.

TPS5603 Background: Clear-cell carcinoma (CCC) is an uncommon histotype of ovarian and a rare histotype of endometrial cancer. Prognosis for recurrent disease is poor and response rates to standard chemotherapy are < 10%. Ovarian CCC (OCCC) is biologically different from other ovarian cancer histotypes but shares features with renal CCC, including upregulation of angiogenesis pathways; inhibition of angiogenesis may thus be of benefit in OCCC. Nintedanib is a well-tolerated, potent, orally-available, kinase inhibitor targeting VEGFR 1-3, PDGFR α and β, and FGFR 1-3. This is the first randomised trial in relapsed OCCC and the first to include a cohort of endometrial CCC (ECCC). Methods: NiCCC is an international randomized phase II trial of nintedanib versus physician’s choice chemotherapy. Standard arms for OCCC are paclitaxel (80mg/m2) IV d1, 8, 15 q28; pegylated liposomal doxorubicin (40 mg/m2) IV q28 or topotecan 4 mg/m2 IV d1, 8, 15 q28, and carboplatin (AUC 5) and paclitaxel (175 mg/m2) IV q21, or Doxorubicin (60 mg/m2) IV q21 for ECCC. The experimental arm is nintedanib 200mg PO bd continuously until progression. Primary endpoint is progression free survival (PFS). The study is designed to detect an increase in median PFS from 3 to 5 months in OCCC with > 90% power, 20% 1-sided significance. 90 OCCC patients and up to 30 ECCC patients will be included to gain initial data in this rarer group. Eligibility includes prospective central pathology review; ≥ 1 line of platinum-based chemotherapy and, in OCCC, progression within 6 months of last platinum; ECOG PS ≤ 2; adequate hepatic, bone marrow, coagulation and renal function. Archival and fresh tumour, plasma and circulating endothelial cell samples are being collected for translational studies. The study is open in the UK. 6 patients have been recruited. The study will open internationally in 2016 in collaboration with three co-operative groups, NSGO, GINECO and EORTC. The study is sponsored by NHS Greater Glasgow and Clyde and funded by Cancer Research UK (Grant ref: C8361/A15600) and an investigator-led study grant from Boehringer Ingelheim. ISRCTN No: ISRCTN50772895. Clinical trial information: ISRCTN50772895.

ObjectivePatients with irresectable granulosa cell tumors (GCTs) often receive chemotherapy. The effectiveness of this approach, however, is uncertain. The aim of our study was to assess the response rate to chemotherapy for residual and recurrent inoperable GCT.MethodsAll consecutive chemotherapy-naive patients in 3 referral hospitals who were treated with chemotherapy for residual or recurrent GCT between 1968 and 2011 were included. Main outcome was the response according to Response Evaluation Criteria in Solid Tumor criteria. A literature search in MEDLINE through PubMed was performed, from inception to August 19, 2013.ResultsTwenty-seven patients with a GCT who received chemotherapy were identified. Eighteen patients were not evaluable because they had either no measurable disease, or no imaging was performed before and after chemotherapy. One of the 9 evaluable patients (11%) had a complete response, and 1 patient (11%) had a partial response, resulting in a response rate of 22% (95% confidence interval, 0%–49%). Seven patients (78%) had stable disease (range, 2–50 months), and none had progressive disease. Fifteen studies that assessed response rates to chemotherapy on measurable disease in a total of 224 patients showed a response rate of 50% (95% confidence interval, 44%–57%). Strict criteria of response, however, were not uniformly applied in the majority of these published series.ConclusionsIn the present study, we present only a moderate beneficial effect of chemotherapy in patients with irresectable GCT with measurable disease. Comparison with previous studies is hampered by a lack of standardized response evaluation in the majority of studies. Given the toxicity of platinum-based chemotherapy, administering this treatment should be a well-considered decision.

e16504 Background: Pts with rCC in PIA might benefit from cDDP plus HT. Lap inhibits the intracellular tyrosine kinase domain of the epidermal growth factor receptor (EGFR) and HER2. Overexpression of EGFR and HER2 is often seen in pts with CC and might be involved in chemotherapy resistance. Besides, preclinical data suggest a synergistic effect of combining cDDP and Lap. Therefore, this phase I dose-escalation study was performed to determine the maximum tolerated dose (MTD) of Lap added to fixed doses of cDDP and HT. Methods: Pts with rCC in PIA, adequate organ function and ECOG performance status 0-1 were scheduled for 6 weekly administrations of 70 mg/m2cDDP plus locoregional HT. Daily Lap was added on days 1-56, starting at a dose-level of 1000 mg. The MTD was defined as the highest dose where ≤1/6 pts experienced dose-limiting toxicity (DLT). Safety, pharmacodynamics (PhD) and response were assessed. Results: Eight pts were treated. The first 4 pts (2 each at dose 1000 mg and 750 mg) experienced DLT. Of the 4 pts treated at dose level -2 (500 mg), only 1 pt was able to complete the treatment as planned, 2 pts experienced a DLT and 1 pt was not evaluable (NE), because of early progressive disease (PD) (see Table). In the evaluable pts 1 PD, 4 stable diseases and 2 partial responses (PR) were observed. One patient with PR had a resection of the local recurrence. Analysis of the resected specimen showed a pathological complete response (pCR). Enumeration of circulating endothelial cells measured at baseline and during therapy did not show consistent results. The same applied for the PhD on Ki-67, p27Kip1and EGFR in pretreatment and on-therapy skin biopsies. Conclusions: It is not feasible to combine Lap with fixed doses of cDDP and HT in pts with rCC in PIA mainly due to increased cDDP-related toxicity. The observed pCR is intriguing and warrants further investigation of combining HER2-blockade and cDDP/HT. Clinical trial information: NL24464.078.08. [Table: see text]

e16547 Background: MA can compromise QoL in pts with OC. The safety and efficacy of catumaxomab in pts with MA due to EpCAM+ carcinomas where standard therapy was not available, not effective or no longer feasible was confirmed in a phase III trial comparing a 3-h intraperitoneal (i.p.) infusion with and without prednisolone premedication (Sehouli, ASCO 2012). Pts with OC who received subsequent CTX after treatment with catumaxomab (post-catumaxomab CTX) were analysed separately. Methods: OC pts in both treatment arms were pooled. The efficacy parameters time to next puncture (TTPu), puncture-free survival (PuFS) and OS were evaluated in relation to post-catumaxomab CTX. Results: 42/109 (39%) pts with MA due to OC received post-catumaxomab CTX, which included a platinum-containing regimen in 19 pts (17%). 21/109 (19%) received >1 post-catumaxomab CTX regimen. Pts with any post-catumaxomab CTX compared with those without CTX had significantly prolonged OS (median 273 vs 81 d, HR 0.24, p<0.0001) and PuFS (median 138 vs 43 d, HR 0.46, p = 0.0002). The difference in TTPu was not significant (223 vs 110 d, HR 0.68, p = 0.1788). Pts with >1 post-catumaxomab CTX compared with 1 post-catumaxomab CTX had significantly prolonged OS (480 vs 167 d, HR 0.20, p < 0.0001). The difference between the groups with 1 and >1 post-catumaxomab CTX in PuFS (153 vs 123 d, HR 0.64, p = 0.1804) and TTPu (153 vs 169 d, HR 1.52, p = 0.3600) was not significant. Pts who received platinum-containing post-catumaxomab CTX had significantly prolonged OS compared with those who received post-catumaxomab CTX without platinum (462 vs 169 d, HR 0.32, p = 0.0026). The difference between the groups with and without platinum in PuFS (153 vs 123 d, HR 0.76, p = 0.4448) and TTPu (153 vs 229 d, HR 1.68, p = 0.2373) was not significant. Conclusions: The data indicate that pts with MA due to OC who are able to receive CTX after catumaxomab treatment have significantly prolonged survival compared with pts who could not receive CTX. Further trials have been initiated to identify the best patient population to receive i.p. catumaxomab followed by subsequent CTX.

Background: Cisplatin-based chemotherapy (etoposide 100 mg/m(2) days 1-5, methotrexate 300 mg/m(2) day 1, cyclophosphamide 600 mg/m(2) day 1, actinomycin D 0.6 mg/m(2) day 2 and cisplatin 60 mg/m(2) day 4, EMACP) was compared to EMA/CO (etoposide 100 mg/m(2) days 1-2, methotrexate 300 mg/m(2) day 1 and actinomycin D 0.5 mg i.v. bolus day 1 and 0.5 mg/m(2) day 2, alternating with cyclophosphamide 600 mg/m(2) day 8 and vincristine 1 mg/m(2) day 8) for the treatment of high-risk gestational trophoblastic neoplasia (GTN).Patients and methods: In the Netherlands, 83 patients were treated with EMACP and 103 patients with EMA/CO. Outcome measures were remission rate, median number of courses to achieve normal human chorionic gonadotrophin (hCG) concentrations, toxicity, recurrent disease rate and disease specific survival.Results: Remission rates were similar (EMACP 91.6%, EMA/CO 85.4%). The median number of courses of EMA/CO to reach hCG normalisation for single-agent resistant disease and primary high-risk disease was three and five courses, respectively, compared to 1.5 (p = 0.001) and three (p < 0.001) courses of EMACP. Patients treated with EMACP more often developed fever, renal toxicity, nausea and diarrhoea compared to patients treated with EMA/CO. Patients treated with EMA/CO more often had anaemia, neuropathy and hepatotoxicity.Conclusion: EMACP combination chemotherapy is an effective treatment for high-risk GTN, with a remission rate comparable to EMA/CO. However, the difference in duration of treatment is only slightly shorter with EMACP. Cisplatin-based chemotherapy in the form of EMACP in this study was not proven more effective than EMA/CO. (C) 2012 Elsevier Ltd. All rights reserved.

5060 Background: A pooled analysis of efficacy with Tr as second/third line in 295 ROC pts demonstrated a median time to progression (TTP) of 4.6 months (mo) (McMeekin, ASCO 2007). Pts sensitive to platinum with a PFI > 6 m (PS), reached a TTP of 6.0 mo, and an overall response rate (ORR) of 36.4% (45.5% in pts with ≥ 2 prior lines). This subanalysis is focused in ROC pts with partially platinum sensitive (PPS) disease, i.e. relapsing between 6-12 m after the end of last prior platinum regimen (PFI:6-12 mo). Methods: Of the 295 pts, 103 were PPS). Three Tr schedules were studied: weekly (0.58 mg/m2 3-h ×3 q4w), and two every 3 weeks (1.3 mg/m2 3-h and 1.5 mg/m2 24-h), that were administered to 41%, 34% and 25% patients, respectively. Efficacy and safety in these patients are reported. Results: Baseline characteristics: median age 58 years (35-80), ECOG PS 0/1: 72%/27%; papillary/serous histology 76%; histology grade 1-2/3: 28%/58%; liver involvement 35%. Treatment with Tr induced 4% complete responses (CR), 26% partial responses (PR), and 40% stable disease (SD); median response duration (RD:PR+CR) 5.2 mo.(95%CI: 3.9-5.8). Median TTP was 5.3 mo (95%CI: 3.8-6.2); 44% pts were progression free at 6 mo (95%CI: 34%-54%). In pts with liver metastases CR+PR was 36% with median TTP 5.3 mo (95%CI: 3.7-6.5). The most common adverse events were neutropenia and transaminase elevations, which were manageable and without serious clinical consequences. Conclusions: Tr monotherapy is active in patients with ROC, including patients with PPS disease (PFI 6-12 mo), with a 30% ORR plus 40% SD, with a median TTP of 5.3 mo. Activity was retained in pts with liver metastasis, with 36% ORR and identical TTP. These single-agent results support the findings of the randomized phase III trial OVA-301 where trabectedin + PLD demonstrated superior clinical benefit over PLD alone in the overall population with particularly pronounced efficacy in the PPS cohort. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Johnson & Johnson, PharmaMar Ortho Biotech, PharmaMar Janssen-Ortho, Zeltia-PharmaMar Ortho Biotech, PharmaMar

Serous peritoneal papillary carcinoma (SPPC), though managed according to ovarian cancer therapeutic principles, has been variably considered as an ovarian cancer counterpart, a peritoneal malignancy with distinct characteristics or a cancer of unknown primary (CUP).We systematically reviewed all publications studying molecular pathophysiology, clinical presentation, management and outcome of at least 10 patients with SPPC from 1980 to 2008 in anglophone medical journals and critically analysed the data.Molecular profiling of CUP was performed in eight papers reporting on 211 patients with stage III/IV SPPC by means of immunohistochemistry or PCR-based assays. Twenty-five clinical series, mostly retrospetive, reported management and outcome of 579 patiens with SPPC, in several cases matched to advanced ovarian cancer controls. Though we did not identify statistically significant differences in molecular biology, clinical presentation, management and outcome of SPPC and ovarian cancer cases, some subtle differences emerged: patterns of loss of heterozygosity at several chromosomal loci differed from those seen in ovarian cancer, while the overexpression of the HER2 oncogene was encountered more often. Serous peritoneal tumours affected older patients and were more frequently multifocal or exhibited virulent clonal expansion in metastatic sites. Diffuse micronodular spread formed a high total load of malignancy in omental, peritoneal surfaces, difficult to debulk optimally. Despite effective chemotherapeutic cytoreduction and occasional long-term remissions, SPPC patients survived 2–6 months less than ovarian cancer patients.Patients with SPPC should not be classified in the poor-risk CUP category, in view of the therapeutic and prognostic differences. Still, the assimilation of the SPPC entity by ovarian cancer hindered further research into its genotypic and phenotypic characteristics that may differ from ovarian cancer. Subgroup analyses of large ovarian cancer trials may shed light in this issue.