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Purpose: In patients with ovarian cancer receiving neoadjuvant chemotherapy, the first-line treatment success will depend on both the tumor-primary chemosensitivity and the completeness of interval debulking surgery (IDS). The modeled CA-125 ELIMination rate constant K (KELIM), calculated with the CA-125 longitudinal kinetics during the first 100 chemotherapy days, is a validated early marker of tumor chemosensitivity. The objective was to investigate the role of the chemosensitivity relative to the success of first-line medical–surgical treatment. Experimental Design: The CA-125 concentrations were prospectively measured in the randomized phase II trial CHIVA (NCT01583322, carboplatin–paclitaxel regimen ± nintedanib, and IDS, n = 188 patients). The KELIM predictive value regarding the tumor response rate, likelihood of complete IDS, risk of subsequent platinum-resistant relapse (PtRR), progression-free survival (PFS), and overall survival (OS) was assessed using univariate and multivariate tests. Results: The data from 134 patients were analyzed. KELIM was an independent and major predictor of subsequent PtRR risk, and of survivals. The final logistic regression model, including KELIM [OR = 0.13; 95% confidence interval (CI), 0.03–0.49] and complete IDS (no vs. yes, OR = 0.30; 95% CI, 0.11–0.76) highlights the preponderant role of chemosensitivity on the success of the first-line treatment. In patients with highly chemosensitive diseases, the patient prognosis was driven more by the chemotherapy-induced antitumor effects than by the surgery. Conclusions: The tumor-primary chemosensitivity, assessed by the modeled CA-125 KELIM calculated during neoadjuvant chemotherapy (http://www.biomarker-kinetics.org/CA-125-neo), may be a major parameter to consider for decision-making regarding IDS attempt, and selecting patients for treatments meant to reverse the primary chemoresistance. See related commentary by May and Oza, p. 4432

Background Hypersensitivity reactions (HSRs) to platinum salts (PS) and taxanes (TX) are a challenge to cancer management. Allergy evaluation based on skin tests (ST) and graded challenges can provide a diagnosis of an allergy to a suspected drug and indicate possible treatment with alternative same-class drugs. Objective This study aimed to estimate the negative predictive value of ST in the diagnosis of HSRs to TX and PS. Methods This multicenter study prospectively enrolled patients with a suspected HSR to PS and TX. ST were performed for chemotherapy, drugs of the same pharmacological class, and other agents (latex or cotreatments). For patients with negative ST, a graded challenge was performed by the cancer teams trained in allergy management. Results A total of 119 consecutive patients were included during a 6-year period. ST results were positive for 58% of the cohort: for TX in 7 patients and for PS in 62 patients. Other agents were responsible for 4.2% of cases. Skin cross-reactivity was 50% for TX and 30% for PS. A graded challenge was performed in 14 patients for TX and in 50 patients for PS. Negative predictive values (NPVs) for ST were 100% for TX and 92% for PS, with NPVs for individuals PS of 100% for cisplatin, 89% for oxaliplatin, and 87% for carboplatin. Conclusions ST to PS or TX offered a high NPV, making allergy evaluation a key element in the management of patients with cancer. Graded challenges can be safely performed by oncology teams trained in anaphylaxis management.

Introduction/Background* Endometrial cancer (EC) patients (Pts) with advanced and recurrent disease relapse despite treatment with combination chemotherapy and have a short progression-free survival (PFS). Nintedanib (N) is a potent, orally available triple receptor tyrosine kinase inhibitor targeting VEGFR 1–3, PDGFR α/β, and FGFR 1–3. This study explored the preliminary efficacy of nintedanib in EC. Methodology The primary objective of this placebo-controlled, randomized study was to evaluate efficacy defined by median PFS of concomitant and maintenance N against placebo (P) in combination with chemotherapy. Patients with histologically confirmed stage IIIC2 or IVA & B or relapsed after adjuvant therapy for stage I-III disease; prior surgery; adjuvant chemotherapy; radiation therapy; hormonal therapy in metastatic setting; with measurable/non-measurable disease were permitted. Pts were randomized 1:1 to receive N 200mg or P, twice daily days 2–21 during chemotherapy (six cycles of Carboplatin (AUC5) and paclitaxel (175mg/m2) every 21 days) and continuously in maintenance phase. N/P was continued until disease progression, unacceptable toxicity, or withdrawal of consent. Stratification by stage of disease, prior adjuvant chemotherapy and measurable/non-measurable disease. This is an ENGOT Model A study. Clinical trial information: NCT02730416. Result(s)* 146 of 148 pts were eligible for PFS: 72N/74P; mean age 66yrs; FIGO stage III 18%, IV 42%, recurrent 40%; follow-up 30 mo. N added to chemotherapy did not improve PFS (119 events) as compared to chemotherapy plus P: median for N 8.3 vs. for P 7.2 mo; hazard ratio (HR) adjusted for stratification factors 1.03; 95% confidence interval (CI),[0.71 to 1.48]; p0.879. Median overall survival (85 events) for N 20 vs. for P 22 mo; HR: 1.10; CI: 0.72–1.69; p0.665. Treatment-emerged grade 3–4 adverse events were higher in N vs P arm: liver function tests 13%/0%; diarrhea 12%/6%; neutropenia 21%/14%; asthenia 4%/1%. Patient-reported outcomes will be reported. Conclusion* Addition of nintedanib to chemotherapy did not improve PFS nor OS. This regimen cannot be recommended to undergo further testing in a phase III trial.

Introduction/Background* As stated by ESGO-ESMO, there is a need for indicators of chemotherapy efficacy in ovarian carcinoma patients treated in first-line setting (Colombo et al, IGCS, 2020). The pathological chemotherapy response score (CRS) and the modeled CA-125 KELIM during neo-adjuvant chemotherapy were reported as potential markers. Moreover, changes in tumor infiltrating lymphocytes (TILs) after neo-adjuvant chemotherapy were reported as a prognostic factor (Leary et al, Cancer Immunol Immunother, 2021). We studied the relationships between changes in TILs, the pathological response (pR) and KELIM in patients treated with neo-adjuvant chemotherapy +/- interval debulking surgery (IDS) from CHIVA phase II trial. Methodology The patients were enrolled in the randomized phase II trial CHIVA (NCT01583322, neo-adjuvant carboplatin-paclitaxel +/- nintedanib, +/- IDS, n=188 patients). KELIM were previously calculated (You et al CCR 2020). The 30 patients with the highest KELIM (very chemosensitive) or the lowest KELIM (poorly chemosensitive) were selected. HE-stained sections from available tissue blocks at baseline and after chemotherapy were analyzed for stromal TILs (sTILs, surface of the tumor stroma occupied by lymphocytes) and intra-epithelial TILs (ieTILs, brisk or non-brisk). The pathological response (pR) was assessed on the most tumoral available tissue block obtained after chemotherapy (good response if extensive fibrous changes with no or isolated tumor cells, or Result(s)* No relationships between KELIM and TILs infiltrates on baseline tumor samples were found. However, strong associations were found between KELIM and TIL infiltrates after neo-adjuvant chemotherapy for sTILs (median KELIM for sTILs 0-5% vs >5%: 0.28 versus 1.32, P Conclusion* High consistency was found between the modeled CA125 KELIM calculated during the first 100 days of neo-adjuvant chemotherapy and the pathological response, consistent with their values as indicators of the tumor chemosensitivity in first-line setting. Moreover, TILs changes were strongly associated with chemosensitivity, opening hypotheses about the mechanisms of chemosensitivity, and immunotherapy opportunity.

Anemia is common in oncology and negatively impacts quality of life. However, there is lack of knowledge about iron deficiency (ID) epidemiology. The aim of this study was to prospectively assess iron status in patients with locally advanced or metastatic cancer beginning chemotherapy. In this prospective, multicenter cohort study, anemia and ID were evaluated in patients with locally advanced or metastatic solid tumors and lymphoma before starting chemotherapy. Blood samples were collected at inclusion (W0), 6 weeks (W6), and 12 weeks (W12). Prevalence was evaluated in the general population, according to tumor location and was correlated with tumor response. One hundred twenty-nine patients were enrolled between 2013 and 2015; 119 had solid tumors and 10 lymphomas. At W0, there were no significant difference between locations with a prevalence around 50–60% (range 47.2–70.4%) and only a trend for colorectal cancer (70.4%, P = 0.069) due to a higher prevalence of absolute ID (18.5%). Prevalence of ID+ decreased between W0 and W6 and remained stable until W12 due to the proportion of patients with ID and without anemia. However, anemia prevalence increased during W0 and W6 and remained stable to W6 from W12 due to patients with anemia but without ID. A significant correlation between tumor response and ID prevalence was found (P = 0.036). We confirm the high prevalence of ID and anemia in cancer patients. ID status is correlated to tumor response providing a strong rationale for iron monitoring during cancer management.

Objective. To analyze the safety and efficacy of niraparib in patients aged >= 70 years with recurrent ovarian cancer in the ENGOT-OV16/NOVA trial. Methods. The trial enrolled 2 independent cohorts with histologically diagnosed recurrent ovarian, fallopian tube, or peritoneal cancer who responded to platinum rechallenge, on the basis of germline breast cancer susceptibility gene mutation (gBRCAmut) status. Patients were randomized 2:1 to receive niraparib (300 mg) or placebo once daily until disease progression. The primary endpoint was progression-free survival (PFS) by blinded independent central review. Adverse events (AEs) of special interest were based on the known safety profile of poly(ADP-ribose) polymerase inhibitors. Results. Patients aged >= 70 years in the gBRCAmut cohort receiving niraparib (n = 14) had not yet reached a median PFS compared with a median PFS of 3.7 months for the same age group in the placebo arm (hazard ratio [HR], 0.09 [95% confidence interval (CI), 0.01 to 0.73]). Non-gBRCAmut patients aged >= 70 years receiving niraparib (n = 47) had a median PFS of 11.3 months compared with 3.8 months in the placebo arm (HR, 0.35 [95% CI, 0.18 to 0.71]). Median duration of follow-up in the niraparib arm was 17.3 months in patients >= 70 years and 17.2 months in patients = 70 years population. The most common grade >= 3 AEs in patients >= 70 years were hematologic: thrombocytopenia event (34.4%), anemia event (13.1%), and neutropenia event (16.4%). Conclusions. For patients >= 70 years of age receiving niraparib as maintenance treatment in the ENGOT-OV16/NOVA trial, PFS benefits and incidence of any grade or serious treatment-emergent AEs were comparable to results in the younger population. Use of niraparib should be considered in this population., TESARO, Inc.

Objective - We have previously shown that epithelial ovarian cancer (EOC) and its treatments have negative effects on long-term quality of life (QoL) and fatigue. The present multicenter study investigated the main menopausal symptoms and gynecological management of EOC survivors (EOCS). Methods - 166 patients with relapse-free ≥3 years after the end of treatment attended a consultation with a gynecologist, including a questionnaire related to vasomotor symptoms (VMS) and sexuality, a clinical examination, a blood sample and an osteodensitometry. QoL, fatigue, insomnia and mood disorders were measured with validated questionnaires and correlated to VMS. VMS and QoL were assessed according to natural menopause (NM) or surgical menopause (SM). Results - Mean age at the survey was 62 [21–83] years and stage III/IV (48%). Mean delay since the end of treatment was 6 years. Fifty-nine patients (36%) had SM. Half of patients reported VMS. Seventy-two percent of EOCS with SM had VMS compared to 41% with NM (P < .001). VMS were not associated with poor global QoL, fatigue, insomnia or mood disorders. Two-thirds of EOCS reported a decrease in libido. Patients with SM showed a greater decrease in libido than NM (P < .02). Fourteen percent of them had osteoporosis and 50% osteopenia. Among the 85 patients with VMS, 80 did not receive HRT after cancer treatment. At the time of the survey, only 7 (4%) patients were receiving hormone replacement therapy (HRT). Conclusions - VMS and sexual disorders are frequently reported by EOCS, particularly among patients with SM. Most EOCS with menopausal symptoms could benefit from HRT to improve these symptoms.

Background Because of the rarity of the condition, studies concerning the management of patients with squamous cell carcinoma of the anus with distant metastasis are scarce. The available studies indicate poor outcomes with exclusive chemotherapy. Objective Our aim was to evaluate the impact of multidisciplinary treatment on overall survival among patients presenting with metastatic squamous cell carcinoma of the anus. Design This was a retrospective study. Settings The study was conducted at a single French institution between 2000 and 2014. Patients Consecutive patients with histologically proven, newly diagnosed, or recurrent metastatic squamous cell carcinoma of the anus were included. Interventions Study interventions included multimodal therapy combining systemic chemotherapy and local ablative treatment to remove all metastases through surgery, radiofrequency ablation, or radiotherapy. Main outcome measures The primary outcome measure was overall survival. Results Fifty patients (median age, 62 years; men/women: 8/42) fulfilled the inclusion criteria, and 39 were available for Response Evaluation Criteria in Solid Tumors. Forty had metastatic relapse after previous treatment of localized disease, and 10 presented with synchronous metastasis. P16 status was not available. Patients received at least 1 chemotherapy regimen, including 5-fluorouracil-mitomycin C (n = 22), cisplatin-5-fluorouracil (n = 20), or 5-fluorouracil alone (n = 3). Thirteen also had surgical metastasectomy, 11 had radiotherapy, and 6 had radiofrequency ablation. Median overall survival was 20.0 months (95% CI, 18.2-21.8 mo), and median time to failure of strategy was 6.0 months (95% CI, 2.9-9.1 mo). Overall response rate was 56% (95% CI, 40%-73%). Outcomes from the 5-fluorouracil-mitomycin C and cisplatin regimens did not statistically differ. Patients treated with multimodal therapy had a median overall survival of 22.0 months (95% CI, 15.3-28.6 mo) versus 13.0 months (95% CI, 9.5-16.5 mo; p = 0.002). Median time to failure of strategy was 10.0 months (95% CI, 4.2-15.7 mo) versus 5.0 months (95% CI, 2.8-7.2; p = 0.007). After 2 years, 40% of patients with multimodal treatment and 20% of those without ablative treatment were alive. Limitations This study is limited by its retrospective design and modest sample size. Conclusions Stage IV squamous cell carcinoma of the anus outcomes are poor, but first-line chemotherapy can enable good response rates. Other treatment modalities, including surgery, radiotherapy, and thermoablation, should be considered, because they may provide a survival advantage. See Video Abstract at http://links.lww.com/DCR/A336.

Few data are available on long-term fatigue (LTF) and quality of life (QoL) among epithelial ovarian cancer survivors (EOCS). In this case-control study, we compared LTF, symptoms and several QoL domains in EOCS relapse-free ≥3 years after first-line treatment and age-matched healthy women.EOCS were recruited from 25 cooperative GINECO centers in France. Controls were randomly selected from the electoral rolls. All participants completed validated self-reported questionnaires: fatigue (FACIT-F), QoL (FACT-G/O), neurotoxicity (FACT-Ntx), anxiety/depression (HADS), sleep disturbance (ISI), and physical activity (IPAQ). Severe LTF (SLTF) was defined as a FACIT-F score37/52. Univariate and multivariate logistic regressions were conducted to analyze SLTF and its influencing factors in EOCS.A total of 318 EOCS and 318 controls were included. EOCS were 63-year-old on average, with FIGO stage I/II (50%), III/IV (48%); 99% had received platinum and taxane chemotherapy, with an average 6-year follow-up. There were no differences between the two groups in socio-demographic characteristics and global QoL. EOCS had poorer FACIT-F scores (40 versus 45, P 0.0001), lower functional well-being scores (18 versus 20, P = 0.0002), poorer FACT-O scores (31 versus 34 P 0.0001), and poorer FACT-Ntx scores (35 versus 39, P 0.0001). They also reported more SLTF (26% versus 13%, P = 0.0004), poorer sleep quality (63% versus 47%, P = 0.0003), and more depression (22% versus 13%, P = 0.01). Fewer than 20% of EOCS and controls exercised regularly. In multivariate analyses, EOCS with high levels of depression, neurotoxicity, and sleep disturbance had an increased risk of developing SLTF (P 0.01).Compared with controls, EOCS presented similar QoL but persistent LTF, EOC-related symptoms, neurotoxicity, depression, and sleep disturbance. Depression, neuropathy, and sleep disturbance are the main conditions associated with severe LTF.

Background: Olaparib is a PARP inhibitor that has shown high response rates and clinical activity in patients with advanced HER2-negative breast cancer (BC) and a germline BRCA1 and BRCA2 mutation. There is also evidence of cellular sensitivity to PARP inhibitors associated to defects in other genes involved in homologous recombination DNA repair (HRR) or mismatch repair pathway (microsatellite instability MSI). Moreover, about 15% of patients with ER+/HER2- metastatic BC have at least 100 mutations in their tumor, leading to genomic instability and potential sensitivity to PARP inhibitors. Several preclinical and clinical studies have suggested the benefit of an association of immune checkpoint blockade, like durvalumab, with PARP inhibitor. Indeed, tumors with BRCA1/2 mutations or other deficiency in HRR have high mutagenic burden and produce a larger number of neoantigens. Most BRCA-associated BC are ER+/HER2-. Although loss of the BRCA gene function is a key driver of oncogenesis in these patients, ER-pathway appears to remain a key target for their therapy. Preclinical data indicate that olaparib may enhance endocrine therapy efficacy and circumvent resistance. Therefore, the combination of durvalumab, olaparib and endocrine therapy could be a therapeutic option for patients with BRCA1/2 mutation or for patients with selected ER+/HER2- advanced BC. Trial design: DOLAF is an open-label, international, multicentric, phase II trial assessing the combination of olaparib, fulvestrant, and durvalumab. Olaparib will be administered orally twice daily at 300 mg. Fulvestrant will be administered as two intramuscular injections of 250 mg (Cycle 1 Days 1 and 15, and Day 1 of each subsequent 28-day cycle). Durvalumab will be started 4 weeks after the first dose of olaparib at 1500 mg intravenous every 4 weeks. Eligibility criteria include: ER+/HER2- metastatic or locally advanced BC with documented germline alteration in BRCA1 or BRCA2 or deleterious germline or somatic alterations implicated in the HRR pathway (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, FANCA, FAND2, FANCL, MRE11A, NBN, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D and RAD54L) or in MSI status or other actionable genes (AKT1, ESR1, FGFR1, FGFR2, FGFR3, and PIK3CA) all based on central tumor next generation DNA sequencing. Patients could have received 1 line of endocrine therapy and/or 1 line of chemotherapy in the metastatic setting.Specific aims: To evaluate the efficacy of the combination in terms of progression-free survival rate at 24 weeks using RECIST v1.1. Secondary endpoints include: safety (according to the NCI-CTCAE v5.0), overall survival, progression-free survival, objective response rate, duration of response in the overall study population and in the germline BRCA mutated population. Statistical methods: Given the lack of safety data from this association, a safety run-in of 6 patients was planned. With an optimum two-stage Simon design,α = 2.5%, β = 5%, p0 (the probability of inefficiency maximum) = 50%, p1 (the probability of minimum efficiency) = 65%, it would be necessary to include 149 evaluable patients. The strategy could be considered sufficiently effective if there are at least 87 successes. According to the established design (including a rate of 5% of patients lost to follow-up or non-evaluable), it will be necessary to include 158 patients. We hypothesized that about 20% of screened patients will have a molecular alteration to allow enrollment. Thus, we need to screen 790 patients. The study is recruiting. The safety run-in is over. By July 1, 2020, 62 patients have been screened and 8 have been treated (NCT04053322). Contact information: DOLAF@unicancer.fr Citation Format: Severine Guiu, Judith Balmana, Lise Roca, Anthony Goncalves, Audrey Mailliez, Frederic Bigot, Thomas Bachelot, Florence Dalenc, Nadine Dohollou, Dominique Genet, Isabelle Desmoulins, Camille Chakiba, Suzette Delaloge, Geraldine Martineau, Veronique Haddad, Philippe Follana. Dolaf- an international multicenter phase 2 trial of durvalumab (medi4736) plus olaparib plus fulvestrant in metastatic or locally advanced er-positive, her2-negative breast cancer patients selected using criteria that predict sensitivity to olaparib (UCBG308) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-13-05.

TPS6109 Background: Advanced endometrial cancer (EC) patients relapse despite treatment with combination chemotherapy and have a short progression-free survival (PFS). Data from the TGCA suggest opportunities to targeting DNA repair in women with EC. Particularly type 4 (High copy number or serous like, with frequent TP53 mutations) and type 2 (microsatellite instability hypermutated) EC can be associated with defects in double strand break DNA repair by homologous recombination (HR) and could potentially be targeted by olaparib. We propose a placebo-controlled, multicenter, two-arm, phase II trial comparing olaparib versus placebo in maintenance therapy after chemotherapy in patients with advanced/metastatic EC. Methods: The primary objective of this trial is to evaluate the efficacy of maintenance olaparib in comparison to placebo after platinum based chemotherapy, defined by PFS according to Recist. Key eligibility criteria include: advanced/metastatic histologically confirmed EC (excepted carcino-sarcoma, small cells& neuroendocrine); prior surgery, adjuvant chemotherapy, radiation and hormonal therapy are permitted; objective or stable response after first-line chemotherapy is mandatory. 147 patients are randomized (2:1) after chemotherapy to receive Olaparib 300mg twice daily or placebo in maintenance after at least 4 cycles of platinum based chemotherapy. Olaparib/placebo is continued until disease progression, unacceptable toxicity, or withdrawal. Stratification is on IHC P53 and MMR status. Primary hypothesis is a 66.7% relative increase in the median PFS rate in the olaparib arm (from 4.5 to 7.5 months), corresponding to a 0.60 Hazard Ratio. Secondary endpoints include PFS according to P53, MMR and NGS HRD status, PFS2, disease specific survival, time to subsequent therapy, overall survival, objective response, disease control rate, patient reported outcomes (assessed via EORTC QLQ-C30 and EORTC QLQ-EN24, EORTC-FA, EQ5D) and safety. Trial is recruiting in France (in February n= 40 randomization). Conclusion: this will be the first study that evaluate the efficacy of olaparib in maintenace after chemotherapy in advanced/metastastic EC, stratified on molecular profil. Clinical trial information: NCT03745950.

Aim: The aim of this study was to determine the rate of breast -onserving surgery (BCS) after neoadjuvant chemotherapy (nCT) in patients initially thought suitable for mastectomy as the only conceivable surgical option. Methods: This retrospective study was conducted in the Cancer Center Antoine Lacassagne in Nice (France). Between 2007 and 2012, 168 patients received nCT. We selected among those only the ones who received nCT (n = 119) in order to facilitate a conservative treatment's surgery (a radical treatment was the single option that could be initially proposed to these patients). Patients presenting with metastatic, inflammatory or multifocal tumors or the ones that could already be eligible for a conservative treatment without any nCT were excluded. Results: Among the 119 patients included, 118 presented an invasive ductal carcinoma, a SBR grade 3 in 54.8% and triple negative breast tumor in 34.4%. The mean tumor size before nCT measured by MRI was 41.6 mm (15-110) and 25.3 mm (0-90) after nCT. Eighty-six of patients (72.3%) underwent a BCS. For 33.6% of these patients, an oncoplastic technique was used. Only 4.3% of the selected patients had to undergo an additional surgery due to insufficient surgical margins during the initial surgery. The median follow-up was 41.1 month (CI95%: 35.2-48.3). Five-years overall survival (OS) and disease-free survival (DFS) were 76% (CI95%: 65-89), 71% (CI95%: 61-82), respectively. The factors significantly affecting the eligibility to BCS were as follows: the MRI tumor's initial size with 34 mm (range: 15-100) for BCS versus 55 mm (range: 23-110) for mastectomy (p Conclusions: nCT for patients with “chemosensitive” breast tumor leads to a significant “mastectomy to BCS” conversion's rate. The type of surgery does not seem to affect the patient's OS and DFS. Oncoplastic procedures allow expandion of patient eligibility for BCS after nCT. Disclosure: All authors have declared no conflicts of interest.

Purpose In platinum-resistant ovarian cancer (OC), single-agent chemotherapy is standard. Bevacizumab is active alone and in combination. AURELIA is the first randomized phase III trial to our knowledge combining bevacizumab with chemotherapy in platinum-resistant OC. Patients and Methods Eligible patients had measurable/assessable OC that had progressed < 6 months after completing platinum-based therapy. Patients with refractory disease, history of bowel obstruction, or > two prior anticancer regimens were ineligible. After investigators selected chemotherapy (pegylated liposomal doxorubicin, weekly paclitaxel, or topotecan), patients were randomly assigned to single-agent chemotherapy alone or with bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until progression, unacceptable toxicity, or consent withdrawal. Crossover to single-agent bevacizumab was permitted after progression with chemotherapy alone. The primary end point was progression-free survival (PFS) by RECIST. Secondary end points included objective response rate (ORR), overall survival (OS), safety, and patient-reported outcomes. Results The PFS hazard ratio (HR) after PFS events in 301 of 361 patients was 0.48 (95% CI, 0.38 to 0.60; unstratified log-rank P < .001). Median PFS was 3.4 months with chemotherapy alone versus 6.7 months with bevacizumab-containing therapy. RECIST ORR was 11.8% versus 27.3%, respectively (P = .001). The OS HR was 0.85 (95% CI, 0.66 to 1.08; P < .174; median OS, 13.3 v 16.6 months, respectively). Grade ≥ 2 hypertension and proteinuria were more common with bevacizumab. GI perforation occurred in 2.2% of bevacizumab-treated patients. Conclusion Adding bevacizumab to chemotherapy statistically significantly improved PFS and ORR; the OS trend was not significant. No new safety signals were observed.

Information concerning management of anal canal cancer among the elderly is scarce and much less abundant than for younger subjects.We retrospectively analysed 115 patients treated for anal epidermoid cancer between 2000 and 2010. The population was divided according to age (70 years and ≥70 years).Of the 115 patients, 81 (70.4%) were70 years old and 34 were ≥70 years (29.6%). Tumour characteristics were identical between the two groups and median follow-up was 62 months. Elderly patients had a less favourable performance status (p=0.001) and fewer had received radiochemotherapy (61.8% vs 82.5%, p=0.004). Treatment-related grade 3 and 4 hematologic toxicity was observed more often among elderly subjects. The results at 5 years were less favourable for overall, disease-specific, and disease-free survival (respectively p=0.002, p=0.001, and p=0.001). For patients treated with a curative intent, at 5 years there was no difference between the two groups in terms of overall survival (p=0.2). However, there was a statistically significant difference in favour of the younger group for disease-free survival and metastasis-free survival.If radiochemotherapy can be delivered to elderly subjects with a good general status, the effects appear less favourable than in younger patients.

Background: Weekly paclitaxel and capecitabine intermittent regimen is a safe and effective combination in first line treatment of MBC including triple negative cancer (Lortholary et al, Breast Cancer Res Treat 2012). In TNMBC, the combination of A with first line Ta or Xel has been shown to improve response rate (RR) and progression-free survival (PFS) (Miller K et al., N Engl J Med 2007, Robert J et al., J Clin Oncol 2011). This phase II study is to evaluate the efficacy and safety of A-TaXel combination in TNMBC. Methods: Patients (pts) with measurable TNMBC were treated in first line until progression with q28 cycles of Ta (80 mg/m2 D1, 8, 15) + Xel (800 mg/m2 bid D1-5, 8-12, 15-19) + A (10 mg/kg D1, 14). Primary end point was best overall RR; secondary were safety, PFS, response duration and overall survival (OS). Results: From 04/2010 to 03/2012, 64 pts were accrued including 2 ineligible pts. Patients characteristics were: median age (56.7 yrs), ECOG PS 0 (55%), histological grade III (61%), previous adjuvant chemotherapy (74%), visceral disease (65%), > 1 metastatic sites (74%). Patients received a median of 6 cycles (1-6), mean 5.1. Grade 3-4 neutropenia, anemia and thrombopenia were 23%, 4% and 16% respectively with febrile neutropenia in 5% of pts. G-CSF support was observed in 7% of cycles. Most frequent non hematologic toxicities were alopecia (gr2 40%), hand-foot syndrome (gr2 27%, gr3 13%), nail toxicity (gr2 40%), hypertension (gr3 35%), neuropathy (gr2 26%, gr3 6%), mucositis (gr2 16%, gr3-4 9%), fatigue (gr3 18%, gr4 2%), nausea (gr2 15%, gr3 2%) and thrombosis (gr2 3%, gr3-4 5%). Treatment interruption due to toxicity was 22%, DPD deficiency in one patient, hospitalization 23%. RR was 77%, CR 19%, PR 58%, stable disease 14% and progressive disease 9%. Median response duration was 5.6 months. Median PFS was 7.9 months (6.7-9) and OS 19.2 months (17.3-21.1). Conclusion: A-TaXel is an effective regimen with high RR and manageable toxicity. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-13-07.

BACKGROUND The treatment of anal cancer is based on concomitant radiotherapy and chemotherapy and is associated with a nonnegligible rate of local severe toxicities that can strongly impair the quality of life. OBJECTIVE A retrospective analysis was performed to screen the following factors as potential predictive factors for local skin and digestive toxicities, and as potential prognostic factors for cumulative colostomy incidence: sex, age, tumor size, clinical T and N stage, circumferential extension, invasion of anal margin, HIV status, type of chemotherapy, and type of radiotherapy and dose delivered. METHODS One hundred five patients in our database treated between January 2000 and February 2010 met the eligibility criteria. RESULTS Median follow-up was 54.1 months (range, 1-133). Early and late severe local toxicities occurred in 33 patients (31.4%) and 18 patients (17.1%). The 5-year cumulative rate of colostomy was 26.6%. Predictive factors for local severe early toxicities were as follows: clinical stage III/IV (p = 0.01), no brachytherapy boost (p = 0.003), and use of chemotherapy (p = 0.01). Only brachytherapy retained its independence in multivariate analysis (OR = 4.8 (1.4-16.3), p = 0.01). Human immunodeficiency virus positivity (p = 0.04) was the only predictive factor for late toxicities in univariate analysis; it was linked independently to the occurrence of ulcer (OR = 0.1 (0.01-0.66), p = 0.01). Tumor size ≥4 cm (p < 0.001) and occurrence of grade 2 to 3 ulcers (p < 0.001) were correlated with greater cumulative colostomy incidence. CONCLUSIONS In this cohort, nonuse of brachytherapy was an independent predictive factor for local acute toxicity. Human immunodeficiency virus positivity was the only predictive factor for local late toxicities and strongly influenced the onset of ulcer.

International audience; BACKGROUND: Maintenance strategies beyond response or tumor stabilization with first-line chemotherapy in metastatic breast cancer (MBC) have not been extensively studied. Endocrine therapy combined with continued bevacizumab may be a helpful option for estrogen receptor (ER)-positive MBC. PATIENTS AND METHODS: In this prospective, open-label, phase III study, patients with histologically confirmed ER-positive, HER2-negative MBC and non-progressive disease after 16-24 weeks of taxane plus bevacizumab (T + BEV) were randomized to continuation of T + BEV or maintenance bevacizumab plus exemestane (E + BEV). The primary end point was progression-free survival (PFS) from randomization. To have 80% power to detect an improvement in the 6-month PFS rate (PFS6m) from 50% to 65%, 186 assessable patients were needed for a total of 141 PFS events. An interim analysis was planned after 40% of the required events. RESULTS: The interim analysis with 98 patients showed that the probability of reaching a statistically significant improvement in PFS by the end of the study was only 7%. This led the Independent Data and Monitoring Committee to recommend termination of patient enrollment. After a median of 21-month follow-up of all randomized patients (117 in total), PFS6m from randomization was 67.2% [95% confidence interval (CI) 53.6-77.7] with T + BEV and 55.2% (95% CI 41.5-66.9) with E + BEV [hazard ratio (HR): 1.0, 95% CI 0.7-1.5, P = 0.998]. Median PFS from BEV initiation was 12.5 and 12.3 months in the T + BEV and E + BEV arms, respectively. In the T + BEV arm, taxane was prematurely stopped for the majority of patients (94.9%), mainly due to toxicity (49.2%). Updated data after 35 months' median follow-up showed death rates of 44% and 55% in T + BEV and E + BEV arms, respectively. CONCLUSION: In this trial, maintenance therapy with E + BEV in ER-positive, HER2-negative MBC patients with no evidence of progression after first-line T + BEV did not achieve longer PFS compared with continuation of T + BEV. CLINICALTRIALSGOV: NCT01303679

BACKGROUND The current study was performed to determine the efficacy and safety of first-line combination therapy with bevacizumab, paclitaxel, and capecitabine for triple-negative, locally advanced/metastatic breast cancer (LA/MBC). METHODS Patients with measurable triple-negative LA/MBC who had received no prior chemotherapy for their disease received 4-weekly cycles of paclitaxel (80 mg/m2 on days 1, 8, and 15 for up to 6 cycles) combined with capecitabine (800 mg/m2 twice daily on days 1-5, 8-12, and 15-19) and bevacizumab (10 mg/kg on days 1 and 14) repeated every 4 weeks until disease progression or unacceptable toxicity occurred. The primary endpoint was the objective response rate; secondary endpoints were progression-free survival, duration of response, overall survival, and safety. RESULTS Between April 2010 and March 2012, 62 eligible patients were enrolled. The median age of the patients was 57 years, 74% had received adjuvant chemotherapy, and 65% had visceral metastases. Patients received a median of 6 cycles (range, 1-45 cycles). The objective response rate was 77% (95% confidence interval [95% CI] 66%-88%), including complete response in 19% of patients. The median duration of response was 5.6 months (range, 1.3-27.6 months). The median progression-free survival was 7.6 months (95% CI, 6.3-9.0 months) and the median overall survival was 19.2 months (95% CI, 17.4-20.9 months). The most common grade ≥3 adverse events were hypertension (35% of patients) and neutropenia (23% of patients); 5% of patients experienced febrile neutropenia. Grade ≥2 hand-foot syndrome, alopecia, and nail toxicity each occurred in 40% of patients (adverse events were recorded before every cycle and graded according to Common Terminology Criteria for Adverse Events [version 4.0]). Treatment was interrupted because of toxicity in 22% of patients. CONCLUSIONS A triplet regimen of paclitaxel, capecitabine, and bevacizumab followed by maintenance therapy with capecitabine and bevacizumab demonstrated high activity and manageable safety in this difficult-to-treat population. Cancer 2016;122:3119–26. © 2016 American Cancer Society.

Malignant ascites are the cancer-associated accumulation of fluids in the peritoneal cavity. The neoplasms most frequently associated with ascites are ovarian, breast, colon, stomach and pancreas adenocarcinomas. Symptoms are abdominal distention, nausea, vomiting, anorexia, dyspnea and limbs oedemas. Several pathophysiological mechanisms might be implicated such as peritoneal carcinomatosis, lymphatic vessels' obstruction, portal hypertension or heart failure. Its diagnosis is most often performed in a context of already known neoplasia. Malignant ascites are associated with a pejorative evolution. Ascites which cannot be mobilized or show early recurrence and cannot be prevented by medical treatment are defined as refractory ascites. Therefore, management of refractory malignant ascites takes place in the context of palliative care and aims at improving the quality of life of these patients. This review lists the current data reported on the pathophysiology of malignant ascites and describes the present and future options for refractory malignant ascites management.

Background: Despite current treatment options, metastatic breast cancer (MBC) remains essentially incurable, requiring research on new drugs or combinations to improve survival and quality of life. Patients and Methods: This phase I study was designed to define the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended dose of all-oral tegafur-uracil (UFT)/folinic acid combined with vinorelbine as chemotherapy for MBC. Starting doses were 40 mg/m2/week of oral vinorelbine administered continuously and 250 mg/m2/day of UFT plus 90 mg/day of folinic acid from day 1 to day 28, followed by a 1-week rest period. Results: Ten patients were included. Eight were evaluable for toxicity and antitumor response. The second dose level was shown to be the MTD. At this dose, 2 out of 5 patients receiving oral vinorelbine at 40 mg/m2/week and UFT at 300 mg/m2/day developed DLT consisting of grade 3 asthenia and grade 3nausea despite standard prophylaxis. Other toxicities were grade 1 diarrhea and anemia. There were no treatment-related deaths. Conclusions: The recommended dose for this combination seems to be the first dose level. A stable response was observed for 6 patients (average 33 weeks). This combination appears to be well-tolerated and offers an alternative to intravenous chemotherapy.

Significant progress has been made within the last 15 years in the treatment of advanced colorectal cancer. Bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, has contributed to this progress. However, in most of the published studies, particularly those using bevacizumab, the median age of patients was 75 years. Further studies are required in elderly patients, particularly those aged > 75 years.

Background: Epithelioid hemangio-endothelioma (EHE) is a rare malignant tumor of vascular origin that electively metastasizes to lungs and liver. Case report: We report the case of a 51-year-old woman with metastatic and progressive EHE of the liver. She was successfully treated with daily administration of sunitinib malate, an oral multi-target tyrosine kinase inhibitor, which particularly targets vascular endothelial growth factor (VEGF) receptors. Stabilization has lasted 6 years. We discuss the rationale for using antiangiogenic treatment for EHE. Conclusion: This case adds to a growing body of evidence that suggests that antiangiogenic agents should be considered in patients who present with advanced EHE.

Objective: Treating metastatic pancreatic cancer (MPC) remains a challenging issue. Maintenance therapy is a growing concept used in different types of cancer. Our retrospective analysis aims to evaluate the effectiveness and tolerability of early maintenance capecitabine administrated to patients with MPC treated with first-line FOLFIRINOX. Methods: 103 patients treated for MPC between November 2009 and July 2014 were retrospectively identified in our institution. Among them, 30 patients initially treated with a minimum of 4 and no more than 8 cycles of FOLFIRINOX, without signs of progression (every 14 days), received maintenance therapy with capecitabine until progression. Upon first progression (first progression-free survival, PFS1), patients were retreated with FOLFIRINOX or another scheme until second progression (second progression-free survival, PFS2). Results: Median OS was 17 months. Survival rates were 73% at 1 year (95% CI 0.59-0.91) and 25% at 2 years (95% CI 0.13-0.50). Median PFS1 was 5 months. Twenty-nine patients experienced disease progression during capecitabine treatment (96.7%). After disease progression, median PFS2 was 10 months. Considering the interval between the starting date of FOLFIRINOX treatment and second disease progression, the median time to treatment failure is 17 months. Conclusions: Maintenance with capecitabine seems effective without compromising FOLFIRINOX efficacy and allows obtaining very promising OS and PFS.

TPS5611 Background: Endometrial cancer (EC) patients with advanced and recurrent disease relapse despite treatment with combination chemotherapy and have a short progression-free survival (PFS). With the emerging clinical data on anti-angiogenic agents and with promising results of nintedanib in ovarian cancer, it is apparent to explore its role in EC. Nintedanib is a potent, orally available triple receptor tyrosine kinase inhibitor targeting VEGFR 1-3, PDGFR α/β, and FGFR 1-3. This placebo-controlled, multicenter, two-arm, phase 2 trial compares nintedanib versus placebo as concomitant and maintenance therapy in combination with chemotherapy in patients with advanced or recurrent EC. Methods: The primary objective of this trial is to evaluate efficacy of nintedanib against placebo in combination with chemotherapy, defined by PFS. Key eligibility criteria include: histologically confirmed EC, stage 3C 2 or 4 A & B or relapsed after adjuvant therapy for stage 1-3 disease; prior surgery; adjuvant chemotherapy; radiation therapy; hormonal therapy are permitted; measurable/non-measurable disease. 148 patients will be randomized 1:1 to receive nintedanib 200mg twice daily or placebo days 2-21 during chemotherapy (six cycles of Carboplatin (AUC5) and paclitaxel (175mg/m2) every 21 days) and continuously in maintenance phase. Nintedanib/placebo is continued until disease progression, unacceptable toxicity, or withdrawal. Secondary endpoints include PFS in sub-populations, PFS2, disease specific survival, time to first subsequent therapy, time to second subsequent therapy, overall survival, objective response, disease control rate, patient reported outcoms (assessed via EORTC QLQ-C30 and EORTC QLQ-EN24) and safety. Trial is enrolling patients. The following cooperative groups are participating: NSGO (DK, FIN, SWE, NOR), NOGGO (GER), BGOG (BEL), & GINECO (FRA). Clinical trial information: NCT02730416.

5560 Background: Niraparib is a highly selective poly (ADP-ribose) polymerase (PARP) 1/2 inhibitor (PARPi); in preclinical studies, it concentrates in the tumor relative to plasma to deliver durable, near complete PARP inhibition and persistent antitumor effects.Niraparib demonstrated significantly longer progression free survival (PFS) vs placebo in patients (pts) with recurrent OC who were randomized following a complete response (CR) or partial response (PR) to platinum based chemotherapy in the controlled, double-blind phase 3 ENGOT-OV16/NOVA trial. To more fully characterize the NOVA trial population, we assessed platinum resistance status, defined as a duration of response to platinum < 6 months to the most recent (ultimate) platinum regimen. Analysis was limited to pts in the placebo arm, as inclusion of pts receiving active treatment (niraparib) would have confounded the ability to determine duration of response to platinum alone. Methods: Pts with recurrent OC, no prior PARPi use, ≥2 prior courses of platinum based chemotherapy, and CR or PR to the most recent platinum based chemotherapy were eligible. Pts were assigned to one of two cohorts based on g BRCA testing (g BRCAmut or non-g BRCAmut) and randomized 2:1 within each cohort to niraparib 300 mg or placebo qd until progressive disease (PD). Randomization occurred up to 8 weeks following the last dose of the most recent platinum based chemotherapy. PFS was measured from time of randomization to death or earliest PD as assessed by independent review committee. Estimated probability of pts having disease progression in each cohort and pooled across cohorts 6 months after the last dose of their most recent platinum therapy was calculated using the Kaplan-Meier methodology. Results: 181 pts were randomized to placebo (65 g BRCAmut and 116 non-g BRCAmut). Platinum resistance rate estimates for the g BRCAmut, non-g BRCAmut, and pooled cohorts were 42%, 53%, and 49%, respectively. Conclusions: Approximately half of the pts in the NOVA study, where niraparib treatment met its primary endpoint of prolonging PFS following a response to platinum, had developed platinum resistance to their last line of chemotherapy. Clinical trial information: NCT01847274.

Angiogenesis is a key process in cancer development and has been described has a hallmark of cancer. Two dose-intensities were approved for cancer treatment by the Food and Drug Administration and European Medicines Agency: 2.5mg/kg/week dose equivalent and 5mg/kg/week dose equivalent. While bevacizumab has shown its effectiveness in clinical trials, pharmacodynamics is not fully understood and a dose-effect relationship has not been proven in vivo. Direct trials comparing high or low doses are rare with potential dose-effect toxicity. Discordant data have been reported on the efficacy of doses. This review discusses the dose of bevacizumab via the analysis of studies that led to the approval of bevacizumab in clinical practice. Optimization of doses schemes could reduce potential dose-effect toxicities, potentiate synergetic effects with chemotherapy and permit the prescription to a larger population with a better cost-effectiveness ratio.

e21532Background: Trying to predict the very early death after a CGA is difficult in elderly metastatic cancers. Last year, we presented a clinical score to predict this risk in 815 elderly cancer ...

Purpose To assess early clinical results and evaluate patient satisfaction in case of second conservative treatment (2nd CT) combining lumpectomy plus high-dose rate (HDR) interstitial brachytherapy for patients (pts) presenting with ipsilateral breast cancer recurrence (IBCR). Methods and Materials From June 2005 to July 2009, 42 pts presenting with an IBCR underwent a second lumpectomy with intraoperative implantation of plastic tubes in the tumor bed. After performing the dose distribution analysis on the postimplant CT scan, a total dose of 34 Gy in 10 fractions over 5 consecutive days was delivered. Toxicity evaluation was based on the Common Terminology Criteria for Adverse Events v3.0 criteria. Applying a visual analogic scale (VAS) analysis, patient satisfaction regarding cosmetic result and 2nd CT possibility was performed after the end of brachytherapy. Results Median followup was 21 months (range, 6–50 months) and median age at the time of local recurrence was 65 years (range, 30–85 years). Median delay between primary and recurrence was 11 years (range, 1–35 years). Median recurrence tumor size was 12 mm (range, 2–30 mm). Median number of plastic tubes and planes were nine (range, 5–12) and two (range, 1–3), respectively. Median clinical target volume was 68 cc (range, 31.2–146 cc). Second local control rate was 97%. Twenty-two pts (60%) developed complications. Cutaneous and subcutaneous fibrosis was the most frequent side effect. Median VAS satisfaction score regarding cosmetic result was 7 of 10 (range, 4–9), whereas median VAS satisfaction score for 2nd CT was 10 of 10 (range, 8–10). Conclusion A 2nd CT for IBCR using high-dose rate brachytherapy seems feasible with encouraging results in terms of second local control with an acceptable toxicity. Patient satisfaction regarding the possibility of second breast preservation should be considered.

Peripheral primitive neuroectodermal tumors (PNET) belong to the rare family of primary bone neoplasms. Recent clinicopathological studies have revealed that Ewing's sarcoma and PNET have overlapping features and they are now included in the same classification, the Ewing's sarcoma family of tumors (EFTs). PNET have a marked predilection for the extremities and are very rare in the pelvis. These tumors can occur at any age with a peak of incidence in the second and third decades but are very rare in patients over 40 years.We report the case of a 69-year-old man with PNET sarcoma. Outcome was favorable after combined modality treatment including chemotherapy based on the Memphis protocol - adapted from that used for Ewing's sarcoma in children - and surgery.Our case is uncommon because of the age at diagnosis, the fortuitous way of revelation, and the choice of dose-intense chemotherapy adapted from the Memphis protocol (cyclophosphamide- and doxorubicin-based) for children, which was efficient and safe. It supports the fact that an adult, and even an old patient, with good physical status, may be treated safely and radically even with dose-adapted aggressive chemotherapy.

We report the experience of two French cancer centers in the treatment of oral cavity squamous cell carcinoma (SCC) in patients aged 80 years.Two hundred and sixty patients aged 80 years with a primary oral cavity SCC were included in this retrospective analysis.Sex ratio was near to 1. Tobacco or alcohol intoxication was the main risk factor for 66% of men and 16% of women and leukoplakia, lichen planus, or oral traumatism for 55% of women and 11% of men (p0.0001). Two hundred patients received a loco-regional (LR) treatment with a curative intent (surgery and/or radiotherapy), 29 with a palliative intent and 31 did not receive a LR treatment. Curative treatments were initially planned to be adapted to age in 118 patients (59%). The median disease-specific survival (DSS) was 29 months. In multivariate analysis, the independent prognostic factors for DSS were stage (HR=0.42 [0.24-0.72]), age (HR=0.43 [0.24-0.75]) and performance status (HR=0.50 [0.27-0.95]). The median overall survival (OS) was 14 months. In multivariate analysis, the independent prognostic factors for OS were age (HR=0.52 [0.35-0.79]), stage (HR=0.56 [0.38-0.84]), tumor differentiation (HR=0.60 [0.33-0.93]) and performance status (HR=0.6 [0.37-0.97]). In patients treated with a curative intent, treatment adapted to age was not associated with a decreased overall survival or disease-specific survival as compared with the standard treatment. However, prophylactic lymph node treatment in stages I-II tumors decreased the rate of nodal recurrence from 38% to 6% (p=0.01).This study emphasizes the need for prospective evaluation of standard and adapted schedules in elderly patients with oral cavity cancer.

Radical ablative surgery and radial forearm free flap (RFFF) reconstruction provide promising oncologic and functional results in patients with oral or oropharyngeal cancer.To assess the postoperative outcomes and the oncologic and functional results, with their main predictive factors, after radical ablative surgery and RFFF reconstruction for patients with oral or oropharyngeal cancer.Between 2000 and 2006, we prospectively analyzed the postoperative, oncologic and functional outcomes of all previously untreated patients who underwent this type of surgery.A total of 132 patients were enrolled in this study. There were three RFFF failures. The rate of surgical complications was 20%. The 5-year locoregional control and overall survival rates were 68% and 52%, respectively. Advanced age, high comorbidity index, elevated overall stage and tumoral involvement of the inner part of the cheek were correlated with a lower overall survival rate. A good functional result was obtained for oral diet, speech, mouth opening and aesthetic outcome in 87%, 80%, 86% and 88% of the patients, respectively. High comorbidity index, large flap surface, radiotherapy and tumoral involvement of the mobile tongue were significant predictors of poorer functional or aesthetic outcomes.

Objectives: This prospective study was designed to evaluate quality of life (QOL) after free-flap head and neck reconstruction. Study Design: Prospective study. Methods: Between January 2004 and December 2005, a total of 95 patients underwent microvascular reconstruction of the head and neck at our Institution (Centre Antoine-Lacassagne, Nice, France) and were initially included in this study. The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire and the EORTC Head and Neck Cancer Quality of Life Questionnaire were completed before surgery, and at 6 and 12 months thereafter. Sixty-five patients completed the questionnaires on at least two of the assessment dates. Predictive factors of Quality of Life (QOL) scores at 6 months were researched among the following: age, sex, comorbidity, radiotherapy, tumor recurrence, tumor stage, and type of surgery. Results: Global QOL remained stable over time. Physical, social, and role functioning deteriorated significantly after treatment. Pain decreased markedly. Social eating, senses, and speech difficulties increased significantly at 6 months, but stabilized between 6 and 12 months. Problems concerning mouth opening and social contact augmented progressively until the 12th postoperative month. Sex, type of surgery, and radiotherapy were the main factors influencing QOL 6 months after treatment. Conclusions: Despite some functional impairments, global QOL was preserved after major head and neck ablative surgery and microvascular free-flap reconstruction.

BACKGROUND: EGFR (epidermal growth factor receptor) gene gain assessed by FISH (fluorescence in situ hybridization) has been shown to be predictive of response to EGFR-targeted therapies in patients with non-small cell lung cancer. The aim or our study was to relate the EGFR gene copy number to therapeutic results in patients with metastatic colorectal cancer (CRC) treated with a cetuximab-containing regimen. METHODS: Forty-seven patients with metastatic CRC treated with a cetuximab-containing regimen between August 2004 and September 2006 were included in our study. EGFR status was assessed by immunohistochemistry (IHC) and by FISH on fixed paraffin-embedded sections of tumor specimens. RESULTS: By IHC (n = 47), 39 patients (83%) had EGFR-positive tumors. EGFR gene copy gain was detected in 8 (19.5%) of 41 tumors. Neither EGFR expression assessed by IHC nor EGFR gene copy gain assessed by FISH were statistically significantly correlated with objective response rate, disease control rate, progression-free survival, and overall survival. Of the 33 patients whose tumors were FISH negative, 8 patients (24.2%) had a partial response, and 10 (30.3%) had stable disease. CONCLUSIONS: EGFR FISH analysis does not seem to be a sufficiently robust test for selecting candidate CRC patients for cetuximab therapy.

Dermatofibrosarcoma protuberans (DFSP) is a rare, dermal neoplasm of intermediate malignancy. It is made of spindle-shaped tumor cells in a storiform pattern positive for CD34. Cytogenetically, DFSP cells are characterized by either supernumerary ring chromosomes composed of sequences derived from chromosomes 17 and 22 or more rarely of translocations t(17;22). These chromosomal rearrangements lead to the formation of a specific chimeric gene fusing COL1A1 to PDGFB. So far, the COL1A1-PDGFB fusion gene remains the sole fusion gene identified in DFSP. However, some observations suggest that genes, other than COL1A1 and PDGFB, might be involved in some DFSP cases. We report in this paper a DFSP case presenting as a unique chromosomal abnormality a complex translocation between chromosomes 5 and 8. This is the first report of a DFSP case where the lack of chromosomes 17 and 22 rearrangement and the absence of COL1A1-PDGFB fusion gene have been demonstrated. Using fluorescence in situ hybridization analysis, we showed that the CSPG2 gene at 5q14.3 and the PTK2B gene at 8p21.2 were disrupted by this rearrangement. Although rare, the existence of cases of DFSP negative for the COL1A1-PDGFB fusion has to be taken in consideration when performing molecular diagnosis for a tumor suspected to be a DFSP.

9511 Background: Trying to predict very early death after a CGA is very difficult in clinical practice. Last year, we presented predictors of early death (Boulahssass et al, 9511, ASCO 2014).The ai...

5538 Background: ANTHALYA study is a randomized non comparative clinical trial to evaluate the efficacy and safety of neoadjuvant chemotherapy associated with bevacizumab. It was a 2:1 randomization to receive carboplatin, paclitaxel with (experimental arm) or without (control arm) bevacizumab in the neoadjuvant setting. The extent of initial carcinomatosis is a major determinant of complete resection but is rarely well described. We report here the extent of carcinomatosis explored by laparoscopy of patients included in Anthalya and its correlation with baseline characteristics. Methods: Non-optimally resectable stage IIIC or IV ovarian cancer patients were eligible for this study. Disease extent was evaluated by a standardized form and the Fagotti score was calculated. Baseline clinical characteristics were compared to trials comparing primary debulking surgery and IDS. Results: This multicenter study was conducted in 15 centers: 205 patients have been screened and 95 patients were included. Median age ...

Aim: There is an important literature supporting the role of staging laparoscopy to predict the chances of optimal cytoreduction but its role to screen patient for inclusion in neoadjuvant therapy clinical trial is unknown. We report here the results of screening by laparoscopy for inclusion in a clinical trial testing the efficacy of bevacizumab in the neoadjuvant settting (Anthalya: A Randomized, Open-label, Phase II Study Assessing the Efficacy and the Safety of Bevacizumab in Neoadjuvant Therapy in Patients With FIGO Stage IIIC/IV Ovarian, Tubal or Peritoneal Adenocarcinoma, Initially Unresectable. NCT01739218). Methods: We are currently conducting a clinical trial to evaluate the efficacy of neoadjuvant bevacizumab and chemotherapy measured by the rate of complete resection, defined as the removal of all macroscopic residual tumour at interval debulking surgery (IDS). Secondary objectives are: safety, Objective Response Rate for the neoadjuvant period and after all courses of treatment and monitoring of CA 125. Before randomization, patients with suspicion of stage IIIC-IV ovarian cancer had a laparoscopy to have a histological assessment of the tumor, to document the FIGO stage and to evaluate resectability for inclusion. Standard pictures and scoring are performed during this laparoscopy and during IDS. We report here the results of screening by laparoscopy. Results: This multicenter study is conducted in 14 centers. Over a 16 month period, 182 and 82 patients have been screened and randomized, respectively. The proportion of screening/inclusion in the paticipating centers ranged from 16% to 100% (mean: 46%). Reasons for non inclusion were resectable tumor (60%), non ovarian/tubal/peritoneal adenocarcinoma histology or contra-indication to carboplatin/taxol/bevacizumab (29%), patient refusal (1%). The screening success was not statistically related to the specialty of the PI in each center (medical oncologist vs surgical oncologist, p = 0.09) or to the volume of patients screened (p = 0.09). Conclusions: In patients with suspicion of ovarian cancer (based on imaging, CA125 and clinical data), screening by laparoscopy resulted in eligibility of 46% of patients for inclusion in a neoadjuvant therapy clinical trial. Resectable tumors was the first reason for non inclusion in this neoadjuvant therapy trial. Disclosure: R. Rouzier: membership on an advisory board; V. Menguy: Employee; Y. Ghazi: Employee;. All other authors have declared no conflicts of interest.

TPS5614 Background: We hypothesize that improving the response rate of stage IIIC or IV and non-optimally resectable ovarian cancer patients to neoadjuvant chemotherapy would improve the optimal de...

9511 Background: The purpose of this study is to analyse predictive factors of early death in older patients with cancer during 100 days after a geriatric comprehensive assessment (CGA) in order to...

6042 Background: Adjuvant RDT-chemotherapy is the standard for resected head and neck squamous cell carcinomas (SCCHN) with adverse histological prognostic factors (AHPF). Despite this treatment, h...

501 Background: Combination of P+BEV significantly improves progression-free survival (PFS) in MBC pts, but is associated with adverse events (AEs), mainly neuropathy and fatigue worsening over tim...

LBA5002^ Background: In three phase III trials in OC (2 front line, 1 PT-sensitive recurrent), BEV + CT → BEV significantly improved progression-free survival (PFS) vs CT alone. AURELIA is the first randomized trial of BEV in PT-resistant OC. Methods: Eligible patients (pts) had OC (measurable by RECIST 1.0 or assessable) that had progressed ≤6 mo after ≥4 cycles of PT-based therapy. Pts with refractory OC, history of bowel obstruction, or >2 prior anticancer regimens were ineligible. After CT selection by the investigator (pegylated liposomal doxorubicin [PLD], topotecan [TOP], or weekly paclitaxel [PAC]), pts were randomized to CT either alone or with BEV (10 mg/kg q2w or 15 mg/kg q3w depending on CT) until progression (PD), unacceptable toxicity, or withdrawal of consent. Pts in the CT-alone arm could cross over to BEV monotherapy at PD. The primary endpoint was PFS by RECIST. Secondary endpoints included objective response rate (ORR), overall survival, safety, and quality of life. The design provided ...

667 Background: Treatment of anal cancer is based on combined radiotherapy and chemotherapy (CT). Some patients present early (2 months) toxicities of grade 3 or greater which can strongly impair quality of life. We aimed to identify predictive factors of toxicities in 106 patients treated in a single center between January 2000 and February 2010. Methods: Retrospective analysis of our databases reported severe local toxicities (grade 3 or higher) during treatment of proven localized epidermoid carcinoma of the anal cancer. The following factors were screened as potential predictive factors: gender, age, irradiation dose, HIV status, type of boost (external vs brachytherapy), circumferential extension, type of chemotherapy, invasion of anal margin, clinical T and N stage, and clinical stage. Results: With a median follow-up of 54.1 months (46.8-61.4) early severe local toxicities occurred in 42 patients (pts) (39.6%) whereas late severe toxicities happened in 21 pts (19.8%). Both early and late toxicities were dominated by proctitis (diarrhea and/or rectal bleeding) (7 pts, 6.6% and 6 pts, 5.6% respectively) and recto-anal epithelial toxicities (27 pts, 25.4% and 17 pts, 16% respectively). Two patients got colostomia because of treatment toxicities (1,8%). Predictive factors of increased early toxicities were as follows: clinical stage III/IV (p=0.04), no brachytherapy boost (p=0.008) and type of CT (no CT, 5.9%, CT, 48.8% p=0.001). Brachytherapy boost and presence of CT retained their independency in multivariate analysis (respectively, p=0.001 and p=0.05). Only HIV positivity (p=0.02) was identified as a predictive factor of late toxicities. HIV positivity (p=0.02), invasion of anal margin (p=0.01) and circumferential extension > 33% (p=0.007) correlated with epithelial ulcer. Invasion of anal margin (p Conclusions: In this cohort absence of brachytherapy boost and CT correlated with more severe early local toxicities whereas HIV positivity was the only predictor of local late toxicities.

e11062 Background: Since its approval in Europe in 2000, trastuzumab (T) has changed HER2-positive metastatic breast cancer (MBC) prognosis. After a durable controlled disease under T based therapy...

e13116 Background: The aim was to describe the PK of Erlo, Cap, and Gem, given in combination in the phase I CAPERGEM trial, performed in advanced pancreatic cancer patients. Methods: This study wa...