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Benefit from maintenance in advanced non-squamous non-small cell lung cancer (NS-NSCLC) might favor switch maintenance after disease stabilization (SD) and continuation after objective response (OR). This trial assessed a maintenance strategy conditioned by response to cisplatin-gemcitabine (CG) with G continuation for patients with OR or switch to pemetrexed (P) for patients with SD as compared with a control arm based on the Paramount regimen.Eligibility criteria: age 18-70 years, ECOG PS 0-1, untreated stage IV NS-NSCLC without EGFR or ALK alteration, ineligibility to bevacizumab. Patients were randomized 1:1 to receive either CG (4 cycles) followed by G maintenance in case of OR followed by P at progression, or switch to P for patients with SD, or 4 cycles of CP followed by P (control arm). Primary endpoint: overall Survival.Between 2012 and 2016, 932 patients were randomized (CG: 467, CP: 465) with well-balanced characteristics. 257 patients (56.7%) in the CG arm received maintenance (G: 142, P: 113) versus 277 patients (59.7%) in the CP arm. Median number of maintenance cycles was 5 for G and P (CG induction) and 4 for P (CP induction). OS adjusted HR was 0.97 (95% CI 0.84, 1.13; p = 0.71) with a median of 10.9 months (CG) versus 10.4 (CP). HR for PFS was 0.95 (95% CI 0.83, 1.09; p = 0.45) with a median of 4.8 months for CG versus 4.5 for CP. Safety profile was as expected.Adapting maintenance strategy according to response to induction chemotherapy does not improve patient outcome.NCT01631136.

In advanced oestrogen receptor-positive, HER2-negative breast cancer, acquired resistance to aromatase inhibitors frequently stems from ESR1-mutated subclones, which might be sensitive to fulvestrant. The PADA-1 trial aimed to show the efficacy of an early change in therapy on the basis of a rising ESR1 mutation in blood (bESR1We did a randomised, open-label, phase 3 trial in 83 hospitals in France. Women aged at least 18 years with oestrogen receptor-positive, HER2-negative advanced breast cancer and an Eastern Cooperative Oncology Group performance status of 0-2 were recruited and monitored for rising bESR1From March 22, 2017, to Jan 31, 2019, 1017 patients were included, of whom 279 (27%) developed a rising bESR1PADA-1 is the first prospective randomised trial showing that the early therapeutic targeting of bESR1Pfizer.

International audience; Purpose: Maintenance chemotherapy is a reasonable choice for patients with metastatic non-small cell lung carcinoma (NSCLC) not progressing after induction therapy with a platinum-based doublet. Nevertheless, there have been no studies dedicated to elderly patients.Patients and methods: We conducted a randomised trial in patients aged 70-89 years, with advanced NSCLC (with neither EGFR mutation nor ALK rearrangement), who had not progressed after four cycles of monthly carboplatin and weekly paclitaxel in order to compare maintenance with either pemetrexed (500 mg/m2 d1, 22) in patients with non-squamous cell carcinoma or gemcitabine (1,150 mg/m2 d1, 8, 22) in squamous cell carcinoma to simple observation. The patients were required to have a performance status (PS) 0-2, mini-mental score >23, and creatinine clearance ≥45 mL/min. The primary end-point was overall survival (OS).Results: 632 patients were enrolled from May 2013 to October 2016. Of the 328 (52.3%) patients randomised after induction therapy, 166 patients were assigned to the observation arm, versus 162 to the switch maintenance arm, 119 of whom received pemetrexed and 43 gemcitabine. The median OS from randomisation was 14.1 months (95% confidence interval [CI]: 12.0-17.0) in the observation arm and 14 months (95% CI: 10.9-16.9) in the maintenance arm (p = 0.72). The median progression-free survival (PFS) from randomisation was 2.7 months (95% CI: 2.6-3.1) in the observation arm versus 5.7 months (95% CI: 4.8-7.1) in the maintenance arm (p < 0.001).Conclusion: Switch maintenance therapy significantly prolonged PFS but not OS and, thus, should not be proposed to elderly patients with advanced NSCLC.

Simple Summary The prognostic assessment of older cancer patients is complicated by their heterogeneity. We aimed to assess the prognostic value of routinely measured inflammatory biomarkers. We performed a pooled analysis of prospective multicenter cohorts of cancer patients aged ≥70. We measured CRP and albumin, and calculated Glasgow Prognostic Score (GPS) and CRP/albumin ratio. The GPS has three levels (0 = CRP ≤ 10 mg/L, albumin ≥ 35 g/L, i.e., normal values; 1 = one abnormal value; 2 = two abnormal values). Overall, 1800 patients were analyzed (mean age: 79 ± 6; males: 62%; metastases: 38%). The GPS and CRP/albumin ratio were independently associated with mortality. The discriminative power of the baseline clinical model was increased by adding GPS and CRP/albumin ratio. Routine inflammatory biomarkers add prognostic value to clinical factors in older cancer patients. Abstract Background: The prognostic assessment of older cancer patients is complicated by their heterogeneity. We aimed to assess the prognostic value of routine inflammatory biomarkers. Methods: A pooled analysis of prospective multicenter cohorts of cancer patients aged ≥70 was performed. We measured CRP and albumin, and calculated Glasgow Prognostic Score (GPS) and CRP/albumin ratio. The GPS has three levels (0 = CRP ≤ 10 mg/L, albumin ≥ 35 g/L, i.e., normal values; 1 = one abnormal value; 2 = two abnormal values). One-year mortality was assessed using Cox models. Discriminative power was assessed using Harrell’s C index (C) and net reclassification improvement (NRI). Results: Overall, 1800 patients were analyzed (mean age: 79 ± 6; males: 62%; metastases: 38%). The GPS and CRP/albumin ratio were independently associated with mortality in patients not at risk of frailty (hazard ratio [95% confidence interval] = 4.48 [2.03–9.89] for GPS1, 11.64 [4.54–29.81] for GPS2, and 7.15 [3.22–15.90] for CRP/albumin ratio > 0.215) and in patients at risk of frailty (2.45 [1.79–3.34] for GPS1, 3.97 [2.93–5.37] for GPS2, and 2.81 [2.17–3.65] for CRP/albumin ratio > 0.215). The discriminative power of the baseline clinical model (C = 0.82 [0.80–0.83]) was increased by adding GPS (C = 0.84 [0.82–0.85]; NRI events (NRI+) = 10% [2–16]) and CRP/albumin ratio (C = 0.83 [0.82–0.85]; NRI+ = 14% [2–17]). Conclusions: Routine inflammatory biomarkers add prognostic value to clinical factors in older cancer patients.

BACKGROUND: Older adults with cancer experience negative long-term functional effects of both cancer and treatments. Exercise may minimize their age-related and cancer-related functional decline. METHODS: We conducted a multicentre open-label 12month randomized clinical trial with two parallel arms including participants aged ≥70years with lymphoma or carcinoma requiring curative treatment. The study started at the beginning of any phase of cancer treatment (surgery, chemotherapy, or radiotherapy). The usual care group (UCG) received the current national recommendations in physical activity (a guideline without specific counselling). The intervention group (IG) received 1year phoned physical activity advice individually adapted to physical assessment (twice a month during the first 6months and then monthly). The primary outcome was the proportion of subjects with a 1year decreased short physical performance battery (SPPB) score of 1 point or more. Physical, cognitive, and clinical secondary outcomes were also investigated. RESULTS: We allocated 301 participants (age 76.7±5.0, female 60.6%) to each group. At baseline, the median SPPB was 10/12 in both groups. Breast was the most frequent tumour site (35.7%). After 1year, 14.0% of participants in the UCG and 18.7% in the IG had a decrease in SPPB score of 1 point or more (P=0.772). At 2years, there was no difference in SPPB, gait speed, International Physical Activity Questionnaire score, and verbal fluency. Subgroup analyses after 2years showed a decline in SPPB for 29.8% of UCG and 5.0% of IG breast cancer participants (P=0.006), in 21.7% of UCG and 6.2% of IG female participants (P=0.019), and in 24.5% of UCG and 11.1% of IG normal nutritional status participants (P=0.009). Falls, hospitalization, institutionalization, and death rates were similar in both groups. CONCLUSIONS: Personalized phoned physical activity advice had not reduced functional decline at 1year but provided preliminary evidence that may prevent physical performance decline at 2years in older adults with breast cancer. © 2019 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders. This work was funded by the National Hospital Program of Clinical Research (Programme Hospitalier de Recherche Clinique 2010) and sponsored by the University Hospital of Bordeaux (CHU Bordeaux). Haritz Arrieta was supported by a fellowship from University of the Basque Country (UPV/EHU).

Introduction Immune-checkpoint inhibitor (ICI) efficacy in patients with NSCLC harboring molecular alterations remains poorly elucidated. This study was undertaken to determine ICI efficacy against BRAF-, HER2-, MET-, and RET-NSCLC in a real-world setting. Methods In this retrospective, multicenter study in ICI-treated BRAF-, HER2-, MET- or RET-NSCLCs, we analyzed clinical characteristics and outcomes: ICI-treatment duration, progression-free survival (PFS), objective response rate, duration of response, and overall survival (OS). Results There were 107 patients with NSCLC (mean age, 65.5 y) included from 21 centers: 37% were never-smokers, 54% were men, and 93% had adenocarcinoma. Among them, 44 had BRAF mutation (V600: 26), 23 had HER2 mutation, 30 had MET mutation, and nine had RET translocation. Programmed cell death ligand 1 (PD-L1) status was known for 70 patients and was greater than or equal to 1% in 34 patients. Before ICI, patients had received a median of one treatment line. Median duration of response, PFS, and OS were 15.4 (95% confidence interval [CI]: 12.6–not reached [NR]) months, 4.7 (95% CI: 2.3–7.4) months, and 16.2 (95% CI: 12.0–24.0) months, respectively, for the entire cohort. The response rates for BRAF-V600, BRAF–non-V600, HER2, MET, and RET-altered NSCLC were 26%, 35%, 27%, 36%, and 38%, respectively. For patients who were PD-L1 negative and those who were PD-L1 positive, PFS was 3.0 (95% CI: 1.2–NR) and 4.3 (95% CI: 2.1–8.5) months, respectively, and OS was 11.7 (95% CI: 4.1–NR) and 35.8 (95% CI: 9.0–35.2) months, respectively. Toxicities were reported in 28 patients (26%), including 11 patients (10%) with a grade greater than or equal to three. Conclusions In this real-world setting, ICI efficacy against patients with BRAF-, HER2-, MET-, or RET-NSCLC seemed close to that observed in unselected patients with NSCLC. Large prospective studies on these subsets of patients are needed.

PURPOSE Tumor deposits (TDs) seem to affect the prognosis of patients with colon cancer (CC). In the seventh edition of the American Joint Committee on Cancer TNM staging system for CC, the presence of TDs is only considered in the absence of lymph node metastases (LNMs). In the era of personalized duration of histopathologic criteria-based adjuvant therapy, this could potentially lead to a decrease in the prognostic prediction accuracy. PATIENTS AND METHODS A post hoc analysis of all pathologic reports from patients with stage III CC included in the IDEA France phase III study (ClinicalTrials.gov identifier: NCT00958737 ) investigating the duration of adjuvant fluorouracil, leucovorin, and oxaliplatin or capecitabine and oxaliplatin therapy (3 v 6 months) was performed. The primary objective was to determine the prognostic impact of TD on disease-free survival (DFS). The effect of the addition of TD to LNM count on pN restaging was also evaluated. A multivariable analysis was performed to establish the association between TD and DFS. RESULTS Of 1,942 patients, 184 (9.5%) had TDs. The pN1a/b and pN1c populations showed similar DFS. TD-positive patients had worse prognosis compared with TD-negative patients, with 3-year DFS rates of 65.6% (95% CI, 58.0% to 72.1%) and 74.7% (95% CI, 72.6% to 76.7%; P = .0079), respectively. On multivariable analysis, TDs were associated with a higher risk of recurrence or death (hazard ratio [HR], 1.36; P = .0201). Other adverse factors included pT4 and/or pN2 disease (HR, 2.21; P < .001), the 3 months of adjuvant treatment (HR, 1.29; P = .0029), tumor obstruction (HR, 1.28; P = .0233), and male sex (HR, 1.24; P = .0151). Patients restaged as having pN2 disease (n = 35, 2.3%) had similar DFS as patients initially classified as pN2. CONCLUSION The presence of TDs is an independent prognostic factor for DFS in patients with stage III CC. The addition of TD to LNM may help to better define the duration of adjuvant therapy.

Background Androgen deprivation therapy (ADT) plus docetaxel is the standard of care in fit men with metastatic castration-naive prostate cancer (mCNPC) following results from GETUG-AFU 15, CHAARTED, and STAMPEDE. No data are available on the efficacy of treatments used for metastatic castration-resistant prostate cancer (mCRPC) in men treated upfront with ADT plus docetaxel for mCNPC. Objective To investigate the efficacy and tolerance of subsequent treatments in patients treated upfront with chemo-hormonal therapy for mCNPC. Design, setting, and participants Retrospective data from the GETUG-AFU 15 phase 3 trial were collected for treatments received for mCRPC. Outcome measurements and statistical analysis For the first three lines of salvage treatment for mCRPC we investigated the biochemical progression-free survival, maximum prostate-specific antigen (PSA) decline, overall survival, and tolerance. Results and limitations Overall, 245 patients received at least one treatment for mCRPC. For docetaxel used in first-line, a PSA decline ≥50% was observed in 25/66 (38%) and in 4/20 patients (20%) who had received upfront ADT alone and ADT plus docetaxel ( p =0.14). The median biochemical progression-free survival was 6.0 mo (95% confidence interval: 3.6–7.7) and 4.1 mo (95% confidence interval: 1.3–4.9), respectively. For docetaxel used in first- or second-line, a PSA decline ≥50% was observed in 36/80 (45%) and in 4/29 patients (14%) who had received upfront ADT alone and ADT plus docetaxel ( p =0.07). PSA declines ≥50% were observed with bicalutamide in 12/28 (43%) and 4/23 patients (17%) who had received upfront ADT alone and ADT plus docetaxel. Among men treated upfront with ADT plus docetaxel who received abiraterone or enzalutamide for mCRPC, 10/19 patients (53%) achieved a PSA decline ≥50%. Few grade 3–4 events occurred. Study limitations include the observational design and retrospective characteristics of this analysis, without standardized therapeutic salvage protocols, and the limited number of patients in some of the treatment subgroups. Conclusions Docetaxel rechallenge following progression to mCRPC after upfront ADT plus docetaxel for mCNPC was active only in a limited number of patients. Available data on abiraterone and enzalutamide support maintained efficacy in this setting. The lack of standardized therapeutic protocols for men developing mCRPC limits the comparability between patients. Patient summary Rechallenging docetaxel at castration-resistance was active only in a limited number of patients treated upfront with chemo-hormonal therapy for metastatic castration-naive prostate cancer. Anticancer activity was suggested with abiraterone or enzalutamide in this setting.

Summary Background Nab-paclitaxel plus gemcitabine has become a standard treatment regimen in patients with metastatic pancreatic adenocarcinoma; however, retrospective data suggest that gemcitabine might be inefficient in 50–60% of patients and thus not an optimum regimen in combination with nab-paclitaxel. We did a phase 2 trial to assess the activity and safety of a new regimen of nab-paclitaxel plus simplified leucovorin and fluorouracil. Methods We did a non-comparative, multicentre, open-label, randomised phase 2 trial in 15 hospitals and institutions in France. Eligible participants were previously untreated patients with metastatic pancreatic adenocarcinoma (previous adjuvant chemotherapy after curative intent resection was allowed if the interval between the end of chemotherapy and relapse was more than 12 months). Patients had to have at least one measurable lesion assessed by CT scan or MRI and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. We randomly assigned participants (1:2) centrally to 28-day cycles of either gemcitabine plus nab-paclitaxel or simplified leucovorin and fluorouracil plus nab-paclitaxel. The randomisation was by minimisation, stratified by centre and ECOG performance status. Drugs were administered in each cycle as follows: nab-paclitaxel (125 mg/m 2 ) and gemcitabine (1000 mg/m 2 ) as 30-min intravenous infusions on days 1, 8, and 15; leucovorin (400 mg/m 2 ) as a 120-min intravenous infusion on days 1 and 15; and fluorouracil (400 mg/m 2 ) as a 5-min bolus intravenous infusion followed by a 46-h continuous intravenous infusion of 2400 mg/m 2 on days 1 and 15. Patients continued treatment until unacceptable toxicity, disease progression, or patient withdrawal. The primary endpoint was progression-free survival at 4 months in the first 72 assessable patients in the leucovorin and fluorouracil group, with a target of 50% for the regimen to be deemed sufficiently active to warrant further study. We did the primary analysis on the modified intention-to-treat (ITT) population, defined as all randomly assigned and assessable patients regardless of their eligibility and received treatments. This trial is registered at ClinicalTrials.gov, number NCT01964534. The trial has ended and we report the final analysis here. Findings Between Dec 12, 2013, and Oct 31, 2014, we randomly assigned 114 patients to treatment: 75 patients to the leucovorin and fluorouracil group and 39 to the gemcitabine group. One patient in the leucovorin and fluorouracil group did not have a 4-month assessment, and was thus excluded from the modified ITT analysis. Median follow-up was 13·1 months (95% CI 12·5–14·1). At 4 months, 40 (56%, 90% CI 45–66) of 72 patients in the leucovorin and fluorouracil group were alive and free from disease progression (21 [54%, 40–68] of 39 patients in the gemcitabine group were also alive and progression-free at 4 months). Grade 3–4 adverse events occurred in 33 (87%) of 38 patients in the gemcitabine group and in 56 (77%) of 73 patients in the leucovorin and fluorouracil group, with different toxicity profiles. The most common grade 3–4 adverse events in the leucovorin and fluorouracil group were neutropenia without fever (17 [23%]), fatigue (16 [22%]), paraesthesia (14 [19%]), diarrhoea (nine [12%]), and mucositis (seven [10%]); in the gemcitabine group they were neutropenia without fever (12 [32%]), thrombocytopenia (seven [18%]), fatigue (eight [21%]), anaemia (five [13%]), increased alanine aminotransferase and aspartate aminotransferase concentrations (five [13%] for both), and paraesthesia (four [11%]). Two participants died; one in the leucovorin and fluorouracil group from septic shock, and one in the gemcitabine group from diabetes compensation with acidosis; these deaths were deemed to be not related to treatment. Treatment-related serious adverse events occurred in 28 (38%) of 73 patients in the leucovorin and fluorouracil group and in 14 (37%) of 38 in the gemcitabine group. Interpretation Nab-paclitaxel plus simplified leucovorin and fluorouracil fulfilled the primary endpoint in that more than the required 50% of our study population were progression-free at 4 months, with a tolerable toxicity profile. This regimen thus deserves further assessment in a phase 3 trial. Funding GERCOR (Groupe Cooperateur Multidisciplinaire en Oncologie) and Celgene through grants to GERCOR.

Background The phase II AFUGEM GERCOR trial aimed to assess the efficacy of a first‐line therapy combining nab‐paclitaxel plus either gemcitabine (gemcitabine group) or simplified leucovorin and fluorouracil (sLV5FU2 group) in patients with previously untreated metastatic pancreatic cancer. Results of progression‐free survival at 4 months (primary endpoint) were in favor of the sLV5FU2 group. This paper presents health‐related quality of life (HRQoL) data as a secondary endpoint. Methods HRQoL was assessed using the EORTC QLQ‐C30 questionnaire at baseline and at each chemotherapy cycle until the end of treatment. The HRQoL deterioration‐free survival (QFS) was used as a modality of longitudinal analysis. QFS was defined as the time between randomization and the first definitive HRQoL score deterioration as compared to the baseline score, or death. Sensitivity analysis was performed excluding death as an event. Univariate Cox models were used to estimate hazard ratios (HRs) and 90% confidence intervals (CIs) of the treatment effect. Results Between 2013 and 2014, 114 patients were randomized in a 1:2 ratio (39 in the gemcitabine group and 75 in the sLV5FU2 group). Patients in the sLV5FU2 group seemed to present longer QFS than those of the gemcitabine group for 14 out of 15 dimensions, with HRs

IF 7.191 (2017); International audience; BACKGROUND:Previous studies showed that high and low body mass index (BMI) was associated with worse prognosis in early-stage colorectal cancer (CRC), and low BMI was associated with worse prognosis in metastatic CRC (mCRC). We aimed to assess efficacy outcomes according to BMI.PATIENTS AND METHODS:A pooled analysis of individual data from 2085 patients enrolled in eight FFCD first-line mCRC trials from 1991 to 2013 was performed. Comparisons were made according to the BMI cut-off: Obese (BMI ≥30), overweight patients (BMI ≥ 25), normal BMI patients (BMI: 18.5-24) and thin patients (BMI

Aflibercept in combination with 5‑fluorouracil (5‑FU)/irinotecan improves overall survival in the second‑line therapy of patients with metastatic colorectal cancer (mCRC). In this study, we evaluated the effects of aflibercept in first‑line therapy with FOLFOX followed by maintenance with fluoropyrimidine. VELVET was a prospective, single‑arm multicenter phase II study (completed). Patients with previously untreated, unresectable, evaluable or measurable mCRC, with an age ≥18 years, and an ECOG performance status of 0‑2 received 6 cycles of modified FOLFOX7 (5‑FU/folinic acid and oxaliplatin) with aflibercept at 4 mg/kg every 2 weeks followed by maintenance therapy with fluoropyrimidine with aflibercept until disease progression or limiting toxicity. The reintroduction of oxaliplatin was performed at first progression. The primary endpoint was progression‑free survival (PFS) at 6 months. From May, 2013 to May, 2014, 49 patients were included and 48 were evaluable for response. In total, 33 patients (67.4%) were alive without progression at 6 months. The Kaplan‑Meier survival 6‑month and 1‑year PFS rates were 79.1 and 36.1%, respectively, and the median PFS was 9.3 months (95% CI, 8.3‑12.5). The objective response rate was 59.2% (N=29/49). The most common (≥10%) grade 3‑4 adverse events were hypertension (23%), fatigue (15%), neutropenia (12%), neuropathy (12%) and stomatitis (10%). Three (6%) treatment‑related deaths occurred: One from stroke, one from pulmonary embolism and one from neutropenic sepsis. On the whole, this study demonstrates the efficacy of aflibercept in combination with an oxaliplatin‑based regimen in the first‑line therapy of patients with mCRC. A strict monitoring of blood pressure and immediate management of hypertension during therapy is mandatory.

Purpose Reduction of adjuvant treatment duration may decrease toxicities without loss of efficacy in stage III colon cancer. This could offer clear advantages to patients and health care providers. Methods In International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France, as part of the IDEA international collaboration, patient with colon cancer patients were randomly assigned to 3 and 6 months of modified FOLFOX6 (mFOLFOX6: infusional fluorouracil, leucovorin, and oxaliplatin) or capecitabine plus oxaliplatin (CAPOX) by physician choice. The primary end point was disease-free survival (DFS), and analyses were descriptive. Results A total of 2,010 eligible patients received either 3 or 6 months of chemotherapy (modified intention-to-treat population); 2,000 (99%) had stage III colon cancer (N1: 75%, N2: 25%); 1,809 (90%) received mFOLFOX6, and 201 (10%) received CAPOX. The median age was 64 years, and the median follow-up time was 4.3 years. Overall, 94% (3 months) and 78% (6 months) of patients completed treatment (fluoropyrimidines ± oxaliplatin). Maximal grade 2 and 3 neuropathy rates were 28% and 8% in the 3-month arm and 41% and 25% in the 6-month arm ( P < .001). Final rates of residual neuropathy greater than grade 1 were 3% in the 3-month arm and 7% in the 6-month arm ( P < .001). There were 578 DFS events: 314 and 264 in the 3- and 6-month arms, respectively. The 3-year DFS rates were 72% and 76% in the 3- and 6-month arms, respectively (hazard ratio [HR], 1.24; 95% CI, 1.05 to 1.46; P = .0112). In the 3 and 6-month arms, respectively, for patients who received mFOLFOX6, the 3-year DFS rates were 72% and 76% (HR, 1.27; 95% CI, 1.07 to 1.51); for the T4 and/or N2 population, they were 58% and 66% (HR, 1.44; 95% CI, 1.14 to 1.82); and for the T1-3N1 population, they were 81% and 83% (HR, 1.15; 95% CI, 0.89 to 1.49). Conclusion IDEA France, in which 90% of patients received mFOLFOX6, shows superiority of 6 months of adjuvant chemotherapy compared with 3 months, especially in the T4 and/or N2 subgroups. These results should be considered alongside the international IDEA collaboration data.

Summary Background The combination of an anti-VEGF or an anti-EGFR-targeted monoclonal antibody with chemotherapy has shown clinical activity in patients with metastatic colorectal cancer. However, combining both anti-VEGF and anti-EGFR antibodies with chemotherapy in first-line treatment resulted in adverse outcomes. We assessed whether the combination of erlotinib, an EGFR tyrosine kinase inhibitor, with bevacizumab could increase the efficacy of maintenance therapy in patients with unresectable metastatic colorectal cancer. Methods This randomised, open-label, phase 3 study was undertaken in 49 centres in France, Austria, and Canada. Eligible patients were aged 18–80 years with histologically confirmed, unresectable metastatic colorectal cancer, WHO performance status 0–2, had received no previous therapy for metastatic disease, and had adequate organ function. Patients without disease progression after bevacizumab-based induction therapy were randomly assigned (1:1) by a minimisation technique to bevacizumab (7·5 mg/kg every 3 weeks) or bevacizumab plus erlotinib (150 mg once daily) as maintenance therapy until progression. All patients were stratified by centre, baseline performance status, age, and number of metastatic sites. The primary endpoint was progression-free survival on maintenance therapy analysed by intention to treat. We report the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00265824. Findings Between Jan 1, 2007, and Oct 13, 2011, 700 eligible patients were enrolled; following induction treatment, patients without disease progression were randomly assigned to bevacizumab (n=228) or bevacizumab plus erlotinib (n=224). At the final analysis, median follow-up was 51·0 months (IQR 36·0–60·0) in the bevacizumab group and 48·3 months (31·5–61·0) in the bevacizumab plus erlotinib group. In the primary analysis (after 231 progression-free survival events), median progression-free survival from randomisation was 5·1 months (95% CI 4·1–5·9) in the bevacizumab plus erlotinib group compared with 6·0 months (4·6–7·9) in the bevacizumab group (stratified hazard ratio [HR] 0·79 [95% CI 0·60–1·06]; p=0·11; unstratified HR 0·76 [0·59–0·99]; p=0·043). In the final analysis, median progression-free survival from randomisation was 5·4 months (95% CI 4·3–6·2) in the bevacizumab plus erlotinib group compared with 4·9 months (4·1–5·7) in the bevacizumab group (stratified HR 0·81 [95% CI 0·66–1·01], p=0·059; unstratified HR 0·78 [0·68–0·96], p=0·019). At the final analysis, median overall survival from maintenance was 24·9 months (95% CI 21·4–28·9) in the bevacizumab plus erlotinib group and 22·1 months (19·6–26·7) in the bevacizumab group (stratified HR 0·79 [95% CI 0·63–0·99], p=0·036; unstratified HR 0·79 [0·64–0·98], p=0·035). The most frequent grade 3–4 adverse events were skin rash (47 [21%] of 220 patients in the bevacizumab plus erlotinib group vs none of 224 patients in the bevacizumab alone group), diarrhoea (21 [10%] vs two [ vs two [ Interpretation Maintenance bevacizumab plus erlotinib might be a new non-chemotherapy-based maintenance option for the first-line treatment of patients with unresectable metastatic colorectal cancer after bevacizumab-based induction therapy. Funding GERCOR and F Hoffmann-La Roche.

BACKGROUND: Toxicity, which is a key parameter in the evaluation of cancer treatments, can be underestimated by clinicians. We investigated differences between patients and physicians in reporting adverse events of androgen deprivation therapy (ADT) with or without docetaxel in a multicentre phase III trial in non-castrate metastatic prostate cancer. METHODS: The 385 patients included were invited to complete a 26-symptom questionnaire 3 and 6months after the start of treatment, among which eighteen symptoms were also assessed by physicians, reported in medical records and graded using the Common Toxicity Criteria of the National Cancer Institute. Positive and negative agreements as well as Kappa concordance coefficients were computed. FINDINGS: Data were available for 220 and 165 patients at 3 and 6months respectively. Physicians systematically under-reported patients' symptoms. Positive agreement rates (at respectively 3 and 6months) for the five most commonly reported symptoms were: 61.0% and 64.3% hot flushes, 50.0% and 43.6% fatigue, 29.4% and 31.1% sexual dysfunction, 24.4% and 14.4% weigh gain/loss, 16.7% and 19.3% for joint/muscle pain. For symptoms most frequently reported as disturbing or very disturbing by patients, the clinicians' failure to report them ranged from 50.8% (hot flushes) to 89.5% (joint/muscle pain) at 3months, and from 48.2% (hot flushes) to 88.4% (joint/muscle pain) at 6months. INTERPRETATION: Physicians often failed to report treatment-related symptoms, even the most common and disturbing ones. Patients' self-evaluation of toxicity should be used in clinical trials to improve the process of drug assessment in oncology. FUNDING: French Health Ministry and Institut National du Cancer (PHRC), Sanofi-Aventis, Astra-Zeneca, and Amgen.

11551 Background: To assess prognostic value of routine biomarkers in older patients with cancer. Methods: A pooled analysis of three prospective multicentre cohorts, ELCAPA, PHRC Aquitaine and ONCODAGE was conducted. Patients aged 70 years or older, with cancer were included. Biomarkers collected were plasmatic C-reactive protein, albumin and a combined score: Glasgow Prognostic Score (GPS). The GPS comprised three categories (0: CRP≤10 mg/L, albumin≥35 g/L; 1: CRP≤10 mg/L and albumin < 35 g/L, or CRP > 10 mg/L and albumin≥35 g/L; 2: CRP > 10 mg/L and albumin < 35 g/L).The primary endpoint was overall survival at 12 months. Multivariable Cox models were used, adjusting for age, sex, localisation, metastatic status, performance status, frailty screening index, the G8. Discriminative properties were assessed using Harrell C index and NRI (Net Reclassification Improvement). Results: Overall 1800 patients were analyzed (ELCAPA: N = 543, PHRC Aquitaine: N = 253, ONCODAGE: N = 1004; mean age: 78.5±5.5 years; 61.7% of men; 37% metastatic; most frequent localisations: breast (34.9%) and colon-rectum (17.7%); 70.7% of patients screened at risk of frailty with G8). Overall survival was 71.1%. GPS was independently associated with death (among normal G8: GPS 1: Hazard Ratio (HR) = 4.48; 95% Confidence Interval (95% CI) = [2.03; 9.89], GPS 2: 11.64 [4.54; 29.81], among abnormal G8: GPS 1: 2.45 [1.79; 3.34], GPS 2: 3.97 [2.93; 5.37]. The addition of GPS to the clinical model (Harell C: 0.82 [0.80; 0.83]) improved discrimination (Harell C: 0.84 [0.82; 0.85], NRI: 11% [5; 19]). Conclusions: GPS could be used in older patients with cancer to help decision-making and prognosis assessment.

3519 Background: Tumor deposits (TDs) are isolated tumor foci in the pericolic, perirectal or mesocolic fat without residual lymph node (LN) tissue. TDs seem to impact the prognosis of stage III colon cancer (CC) patients (pts) but are only considered in TNM staging in the absence of LN metastases (LNM). We aimed at evaluating the prognosis value for disease free survival (DFS)of TDs in International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France phase III study (NCT00958737) that compared 3 versus 6 months of adjuvant FOLFOX or CAPOX for stage III CC pts. Methods: All pathological reports of pts included in IDEA France trial were retrospectively analyzed. DFS according to the presence or absence of TDs was evaluated using Kaplan-Meier estimator. Multivariable Cox model analysis was performed to evaluate the association between TDs and DFS. This analysis did not included immunohistochemical biomarkers. Results: Among the 2022 pts included in IDEA France study, 1942 (96%) were analyzed. 80 pts were excluded: no pathological report (n = 68), pts without treatment (n = 12). TDs were found in 184 pts (9.47%), of whom 74 with N1a/b (40%), 55 with N1c (30%) and 55 with N2 LN stage (30%). All characteristics were similar according to the presence of TDs, except for tumor/node (TN) stage (T4 and/or N2 are more frequent in pts with TDs; p = .0046). The 3-year DFS rates were 65.59% [95% confidence interval (95%CI) 58.04-72.12] and 74.71% [95%CI 72.57-76.71] for pts with and without TDs, respectively (p = 0.0079). In multivariable analysis, TDs were associated with higher risk of recurrence or death (hazard ratio (HR) = 1.36, 95%CI 1.05-1.75, p = .0201), as well as T4 and/or N2 (HR = 2.21, 95%CI 1.03-1.59, p < .001), 3 months of adjuvant treatment (HR = 1.29, 95%CI 1.09-1.52, p = .0029), obstruction (HR = 1.28, 95%CI 1.03-1.59, p = .0233) and male (HR = 1.24, 95%CI 1.04-1.46, p = .0151). Adding TDs count to the LNM count, 35 out of 1454 N1a/b/c CC pts (2.4%) were reclassified as N2 and experienced worse 3 years DFS than confirmed N1 CC pts (p = .0151). Conclusions: TD is an independent and valuable prognostic factor for DFSin stage III CC pts and should be considered whatever the LNM status.

Purpose To determine factors associated with early functional decline during first-line chemotherapy in older patients. Patients and Methods Patients age ≥ 70 years receiving first-line chemotherapy for cancer were prospectively considered for inclusion across 12 centers in France. Functional decline was defined as a decrease of ≥ 0.5 points on the Activities of Daily Living (ADL) scale between the beginning of chemotherapy and the second cycle. Factors associated with functional decline were sought from pretreatment abbreviated comprehensive geriatric assessment, including ADL, Instrumental ADL (IADL), Mini-Nutritional Assessment (MNA), Mini–Mental State Examination (MMSE), Geriatric Depression Scale (GDS15), and Timed Get Up and Go (GUG) test, and from comorbidities (Cumulative Illness Rating Scale–Geriatrics), MAX2 index, and baseline biologic and clinical information. Results Of 364 included patients, 50 experienced functional decline (16.7%; median, 0.5 points). Abnormal preadmission performance status, IADL, GDS15, MMSE, GUG, and MNA were associated with increased likelihood of functional decline (univariate analysis). In the multivariate model adjusted for baseline ADL and MAX2 index, high baseline GDS (odds ratio [OR], 2.16; 95% CI, 1.09 to 4.30; P = .03) and low IADL scores (OR, 2.87; 95% CI, 1.06 to 7.79; P = .04) were independently associated with increased risk of functional decline. Conclusion Our results outline associations between baseline depression, instrumental dependencies, and early functional decline during chemotherapy for older patients. ADL should be sequentially evaluated early during treatment. Baseline evaluation of GDS15 and IADL may be proposed to anticipate this event.

A prospective phase II multicenter study was performed in two steps in paclitaxel-treated ovarian cancer patients in France. A French version of the four-item Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) questionnaire was validated. This was then used to evaluate neurotoxicity in relation to erythropoietin treatment. Patients received standard second-line paclitaxel-based chemotherapy and erythropoietin for anemia. Neurotoxicity and hemoglobin levels were evaluated every cycle with the FACT/GOG-Ntx and NCI-CTCAE. The translated questionnaire was tested in 20 patients to confirm the translation accuracy. The final questionnaire was validated in 98 patients with internal consistency (Cronbach’s coefficient) and item correlation (Pearson’s r coefficient) tests. Neurotoxicity severity was analyzed according to erythropoietin intake (first three cycles versus no or late intake) and correlated with anemia. Patients received a median of six paclitaxel cycles (range 1–9). Neurotoxicity was validated in 484 questionnaires. Internal consistency was excellent with Cronbach’s coefficients of ≥0.89 at inclusion, after 3 cycles and at study end. Inter-question correlation was high with Pearson’s coefficients of 0.65–0.85. FACT/GOG-Ntx and NCI-CTCAE severity scoring was similar. Globally, the incidence of severe neurotoxicity (FACT/GOG-Ntx and NCI-CTCAE) was found significantly higher in patients with severe anemia. Of 98 evaluable patients, 31 received erythropoietin during the first three cycles. Mean hemoglobin level was significantly lower in this group from baseline to cycle 4; however, these anemic patients with early EPO intake did not develop an increase rate of severe neurotoxicity. The French FACT/GOG-Ntx questionnaire is a reliable and valid tool for assessing chemotherapy-induced neuropathy. This study raises the possibility that erythropoietin might play a neuroprotective role when administered with paclitaxel.

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

International audience; BACKGROUND: Several expression array studies identified molecular apocrine breast cancer (BC) as a subtype that expresses androgen receptor (AR) but not estrogen receptor alpha. We carried out a multicentre single-arm phase II trial in women with AR-positive, estrogen, progesterone receptor and HER2-negative (triple-negative) metastatic or inoperable locally advanced BC to assess the efficacy and safety of abiraterone acetate (AA) plus prednisone. PATIENTS AND METHODS: Patients with a metastatic or locally advanced, centrally reviewed, triple-negative and AR-positive (\textgreater/=10% by immunohistochemistry, IHC) BC were eligible. Any number of previous lines of chemotherapy was allowed. AA (1000 mg) was administered once a day with prednisone (5 mg) twice a day until disease progression or intolerance. The primary end point was clinical benefit rate (CBR) at 6 months defined as the proportion of patients presenting a complete response (CR), partial response (PR) or stable disease (SD) \textgreater/=6 months. Secondary end points were objective response rate (ORR), progression-free survival (PFS) and safety. RESULTS: One hundred and forty-six patients from 27 centres consented for IHC central review. Of the 138 patients with sufficient tissue available, 53 (37.6%) were AR-positive and triple-negative, and 34 of them were included from July 2013 to December 2014. Thirty patients were eligible and evaluable for the primary end point. The 6-month CBR was 20.0% [95% confidence interval (CI) 7.7%-38.6%], including 1 CR and 5 SD \textgreater/=6 months, 5 of them still being under treatment at the time of analysis (6.4+, 9.2+, 14.5+, 17.6+, 23.4+ months). The ORR was 6.7% (95% CI 0.8%-22.1%). The median PFS was 2.8 months (95% CI 1.7%-5.4%). Fatigue, hypertension, hypokalaemia and nausea were the most common drug-related adverse events; the majority of them being grade 1 or 2. CONCLUSIONS: AA plus prednisone treatment is beneficial for some patients with molecular apocrine tumours and five patients are still on treatment. CLINICALTRIALSGOV: NCT01842321

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.

Purpose Objective factors for making choices about the treatment of elderly patients with cancer are lacking. This investigation aimed to help physicians select appropriate treatments through the identification of factors that predict early death (< 6 months) after initiation of chemotherapy treatment. Patients and Methods Previously untreated patients greater than 70 years of age who were scheduled for first-line chemotherapy for various types of cancer were included. Baseline abbreviated comprehensive geriatric assessment (aCGA), including the Mini-Mental State Exam, Timed Get Up and Go (GUG), Activities of Daily Living (ADL), Instrumental Activities in Daily Living (IADL), Mini Nutritional Assessment (MNA), Geriatric Depression Scale (GDS15), and comorbidities index (Cumulative Index Rating Scale-Geriatric), was carried out. Prognostic factors of early death were sought from aCGA results and traditional oncology measures. Results A total of 348 patients were included across 12 centers in Southwest France (median age, 77.45 years; ratio of men to women, 1.47; advanced disease, 65%). Abnormal aCGA scores were observed for 18.1% of patients on the ADL, 73.0% of patients on the IADL, 24.1% of patients on the GUG, 19.0% of patients on the MMS, 44.0% of patients on the GDS15, and 64.9% of patients on the MNA. Advanced disease (odds ratio [OR], 3.9; 95% CI, [1.58 to 9.73]), a low MNA score (OR 2.77; 95% CI, [1.24 to 6.18]), male sex (OR, 2.40; 95% CI, [1.2 to 4.82]), and long GUG (OR, 2.55; 95% CI, [1.32 to 4.94] were associated with higher risk of early death. Conclusion In patients greater than 70 years of age with cancer, advanced disease, a low MNA score, and poor mobility predicted early death. We recommend that the MNA and GUG, performed by a trained nurse, be maintained as part of routine pretreatment workup in these patients to identify at-risk patients and to inform the decision-making process for chemotherapy.

Summary Objective Current chemotherapy protocols for gastric cancer present high toxicity. The FOLFIRI regimen has shown promising results with elderly colorectal cancer patients and for gastric cancer patients but this is the first report on elderly gastric cancer patients. Design In this multicenter non-randomized phase II trial, we administered the FOLFIRI chemotherapy protocol (irinotecan [180 mg/m2], fluorouracil [5-FU] [400 mg/m2] and folinic acid 400 mg/m2 or 200 mg/m2 of l-folinic acid) to patients aged over 70 years with locally-advanced or metastatic gastric cancer combined with Comprehensive Geriatric Assessment (CGA). Responses were assessed at 2 months. Results Forty-two patients received eight cycles of the FOLFIRI regimen, with 82.5% of patients showing disease control: 10 patients (26%) showing objective (partial or complete) responses and 23 (57.5%) showing stable disease. One-year overall survival (OS) was 41.5% [95%CI 26.5–56.0] and one-year progression-free survival (PFS) was 31.8% [95%CI 18.4–46.1%]. We observed 10 Grade 3/4 hematologic toxicities with one febrile neutropenia. CGA data demonstrated that geriatric functions were not altered by treatment and that nutritional status improved over treatment. Conclusions Results show excellent disease control and relatively high survival rates with limited toxicity similar to younger patients indicating that this regimen should be considered as a possible treatment in advanced gastric cancer of the elderly.

10031Background: Cancer in older patient favors the loose of physical function. Physical activity could be a key factor to diminish the age and cancer-related decline. Methods: We conducted a multi...

737 Background: Primary tumor sidedness (PTS) could be a predictive maker for treatment efficacy of EGFR inhibitors monoclonal antibodies in patients with wild-type (WT) RAS metastatic colorectal cancer (MCRC), cetuximab having limited efficacy in patients with WT-RAS right-sided tumors. DREAM study demonstrated that adding erlotinib, an oral EGFR tyrosine kinase inhibitor (TKI) to bevacizumab during maintenance therapy improved clinical outcomes (RR, PFS, OS) in patients with MCRC, whatever KRAS status. The aim of this post-hoc analysis is to evaluate the clinical outcomes according to KRAS mutational status and PTS when adding erlotinib to bevacizumab maintenance therapy. Methods: PTS was retrospectively collected in patients from the DREAM phase III trial treated with bevacizumab with or without erlotinib as maintenance therapy for MCRC who have been controlled by induction therapy. The limit for the definition of PTS was splenic flexure, and rectal tumors were considered as left-sided tumors. The primary endpoint was overall survival (OS). Results: Among 452 patients who received maintenance therapy, PTS ascertainment was 84.7% (n = 383) with 265 (71.0%) patients having left-sided primary tumor and 108 (28.9%) having right-sided primary tumors (3 patients had both and tumor location was unknown in 7 patients). Median OS and treatment effect are presented in table 1. Conclusions: The greatest OS benefit of adding erlotinib to bevacizumab maintenance therapy was observed in patients with WT-KRAS and right-sided MCRC, suggesting a clinical impact of the different mechanism of action between EGFR TKI and monoclonal antibodies. Clinical trial information: NCT00265824. [Table: see text]

In the Intergroupe Francophone de Cancérologie Thoracique 0501 trial the carboplatin-paclitaxel chemotherapy increased toxicity (most frequent, decreased neutrophil count, asthenia). We longitudinally compared health-related quality of life (HRQoL) of the two treatment arms.In total, 451 patients aged 70–89 years with advanced non-small cell lung cancer (NSCLC) were randomly assigned to receive carboplatin plus paclitaxel or vinorelbine or gemcitabine. HRQoL was assessed by means of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire at baseline, week 6 and week 18.Using a five-point decrease as the minimal clinically important difference, patients treated with the chemotherapy doublet exhibited a significant longer time until definitive deterioration (TUDD) for two HRQoL dimensions: physical functioning (median TUDD: 2.04 for the doublet versus 1.71 months for monotherapy; log-rank p=0.01) and nausea and vomiting (median: not reached versus 4.83, respectively; log-rank p=0.046). Cox multivariate analysis revealed the carboplatin and paclitaxel arm to be independently associated with longer TUDD for these two HRQoL dimensions. In addition, TUDD didn't significantly differ between the two arms for all the other HRQoL dimensions.The chemotherapy doublet did not reduce TUDD in elderly patients with advanced NSCLC. Moreover, TUDD was prolonged for two HRQoL dimensions, namely physical functioning and nausea and vomiting.

BACKGROUND: The Glass model developed in 2003 uses prognostic factors for noncastrate metastatic prostate cancer (NCMPC) to define subgroups with good, intermediate, and poor prognosis. OBJECTIVE: To validate NCMPC risk groups in a more recently diagnosed population and to develop a more sensitive prognostic model. DESIGN, SETTING, AND PARTICIPANTS: NCMPC patients were randomized to receive continuous androgen deprivation therapy (ADT) with or without docetaxel in the GETUG-15 phase 3 trial. Potential prognostic factors were recorded: age, performance status, Gleason score, hemoglobin (Hb), prostate-specific antigen, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), metastatic localization, body mass index, and pain. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: These factors were used to develop a new prognostic model using a recursive partitioning method. Before analysis, the data were split into learning and validation sets. The outcome was overall survival (OS). RESULTS AND LIMITATIONS: For the 385 patients included, those with good (49%), intermediate (29%), and poor (22%) prognosis had median OS of 69.0, 46.5 and 36.6 mo (p=0.001), and 5-yr survival estimates of 60.7%, 39.4%, and 32.1%, respectively (p=0.001). The most discriminatory variables in univariate analysis were ALP, pain intensity, Hb, LDH, and bone metastases. ALP was the strongest prognostic factor in discriminating patients with good or poor prognosis. In the learning set, median OS in patients with normal and abnormal ALP was 69.1 and 33.6 mo, and 5-yr survival estimates were 62.1% and 23.2%, respectively. The hazard ratio for ALP was 3.11 and 3.13 in the learning and validation sets, respectively. The discriminatory ability of ALP (concordance [C] index 0.64, 95% confidence interval [CI] 0.58-0.71) was superior to that of the Glass risk model (C-index 0.59, 95% CI 0.52-0.66). The study limitations include the limited number of patients and low values for the C-index. CONCLUSION: A new and simple prognostic model was developed for patients with NCMPC, underlying the role of normal or abnormal ALP. PATIENT SUMMARY: We analyzed clinical and biological factors that could affect overall survival in noncastrate metastatic prostate cancer. We showed that normal or abnormal alkaline phosphatase at baseline might be useful in predicting survival.

3500 Background: The IDEA international collaboration was established to combine data from 6 randomized trials to assess whether a 3-month (3M) of oxaliplatin/fluoropyrimidines-based adjuvant chemotherapy (CT) is non-inferior to the 6-month (6M) for 3-year disease free survival (DFS) in stage III colon cancer (CC). Methods: French IDEA randomized patients (pts) between 3M and 6M of CT with mFOLFOX6 or XELOX (physician/pts choice). DFS was estimated using the Kaplan–Meier method and described using 3 years DFS rate. Results: Among 2022 randomized pts between May 2009 and May 2014, 2010 (99.4%) received CT and were enrolled in the mITT population: 49.9 and 50.1% in 3M and 6M, respectively. 99.5% of the mITT pts had stage III (N1: 74.9%; N2: 25.2%); median age 63.9 years; mFOLFOX6: 90% and XELOX 10% of pts. DFS median follow-up is 50.2 months. There were 578 DFS events (314 in 3M and 264 in 6M arm) leading to a 3-year DFS rate of 72.1% in the 3M vs. 75.7% in the 6M (HR=1.24; 95%CI 1.05–1.46, p=0.0112). For pts receiving mFOLFOX6, 3-year DFS rate was 72.0% in the 3M vs. 76.3% in the 6M (HR=1.27; 95%CI 1.07–1.51 p=0.0069). 94.2% and 78.0% of pts completed 3 and 6 months of CT, respectively. Median oxaliplatin doses intensity were 96.9% in 3M and 72.1% in 6M (495.0 and 735.1 mg/m2). By considering the neuropathy grade with 15375 neuropathy longitudinal measurements the overall maximal neuropathy grade 0-1/2/3-4 was 63.6/28.5/7.9% in 3M and 33.4/41.3/25.3% in 6M; p

9003 Background: Benefit coming from maintenance treatment appears greater for switch maintenance in pts with disease stabilization (SD) while it might be larger for continuation maintenance in pts with objective response (OR). This study assessed a maintenance strategy conditioned by response to cisplatin-gemcitabine (CG): continuation maintenance with G for pts with OR and switch maintenance with pemetrexed (P) for pts with SD compared with a control arm using P continuation maintenance following cisplatin-pemetrexed (CP) induction regimen. Methods: Eligibility criteria included age 18-70 years, PS of 0-1, untreated stage IV NSQ NSCLC without EGFR mutation or ALK rearrangement, ineligibility to bevacizumab. Pts were randomized 1:1 to receive either experimental CG arm: CG (4 cycles) followed by G maintenance in case of OR followed by second-line P or switch maintenance with P for pts with SD, or standard CP arm: 4 cycles CP induction regimen followed by maintenance P. Overall survival (OS) was the primary endpoint; secondary endpoints included PFS, response rate and safety. Results: Between Jul 2012 and Jun 2016, 932 pts were randomized (CG: 467, CP: 465). Pts characteristics were balanced between the arms. 255 pts (54.6%) in the CG arm received maintenance treatment (G: 142, P: 113) while 274 pts (58.9%) received P maintenance in the CP arm. Median number of maintenance cycles was 5 for G and 4 for P in both arms. The OS adjusted HR was 0.97 (95% CI 0.84, 1.13; p=0.72); median OS: 10.9m CG vs. 10.4m CP. The HR for PFS was 0.96 (95% CI 0.84, 1.10; p=0.56); median PFS: 5.0m CG vs. 4.7m CP. Safety profile was as expected during induction chemotherapy. During maintenance, grade ≥3 hematological AEs occurred in 28% and 31% of pts in CG and CP, respectively, with febrile neutropenia (2.4% vs. 1.1%), anemia (9.4% vs. 11.7%), thrombocytopenia (6.7% vs. 5.8%). No grade ≥3 non-hematological AEs occurred in >5% of pts except for asthenia (3.9% CG vs. 5.1% CP). Conclusions: Adapting maintenance strategy according to response to induction chemotherapy does not improve patient outcome. Clinical trial information: NCT01631136.

350 Background: Nab-paclitaxel plus gemcitabine regimen (NABGEM) became a standard in first-line patients (pts) with metastatic pancreatic adenocarcinoma (mPAC). The AFUGEM trial evaluated the efficacy and safety of nab-paclitaxel plus simplified LV5FU2 (NABFU). Methods: Main eligibility criteria were: untreated mPAC, ECOG PS≤2. Pts received nab-paclitaxel (125 mg/m2 on d1, 8 and 15) plus gemcitabine (1000 mg/m2 on d1, 8 and 15) or plus simplified LV5FU2 (leucovorin 400 mg/m2, 5FU bolus 400 mg/m2 followed by 2400 mg/m2 given as a 46-hour continuous infusion on d1 and 15), one cycle every 4 weeks in both arms, ratio 1:2, respectively. The primary end point was observed progression-free survival (PFS) rate at 4 months (m). A Fleming 2-stage design was used with a targeted (H1) 4m-PFS rate of 50% in NABFU arm and an uninteresting 35% rate (H0, unilateral alpha of 5% and power of 80%). Results: 114 pts were included: NABGEM n=39, NABFU n=75. Baseline characteristics were well balanced: median age 66 years (45-86), ≥2 metastatic sites 36.8%, ECOG PS 0-1 84.2% and 2 15.8%, at the exception of pain more frequent in the NABFU arm (38.5% vs 56.0%). In mITT population, the observed 4m-PFS rates were of 55.4% [95% CI, 45-63] in NABFU Vs 53.9% [95% CI, 39.6-67.7] in NABGEM. Disease control rates were 65% (95% CI, 53-76) and 62% (95% CI, 45-77) respectively. After a follow-up of 24.3m, median PFS were 5.9 [95% CI, 3.6-7.4] v 4.9 months [95% CI, 2.1-7.7] [HR=0.79, 95% CI: 0.52-1.20]. Grade 3-4 adverse events were more frequent in NABGEM (77% v 87%). At tumor progression, in the NABFU arm, 50 patients (66%) and then 13 patients (17%) received a second and third line of chemotherapy respectively, versus 22 patients (56%) and 6 patients (15%) in the NABGEM arm. Median OS were 11.4 [95% CI, 8.8-16.5] v 9.2 months [95% CI, 6.0-13.6] [HR=0.61, 95% CI: 0.40-0.95], respectively. The 12 and 18-months OS rates in NABFU vs NABGEM arm were 48% Vs 41% and 34% Vs 13%, respectively. Conclusions: Nab-paclitaxel plus simplified LV5FU2 appears at least as active as gemcitabine plus nab-paclitaxel in mPAC. The toxicity profile is safe and tolerable. This regimen deserves evaluation in a phase III trial. Clinical trial information: NCT01964534.

International audience; OBJECTIVE: We tested the effect of dietary advice dedicated to increase intake in older patients at risk for malnutrition during chemotherapy, versus usual care, on one-year mortality. METHOD: We conducted a multicentre, open-label interventional, stratified (centre), parallel randomised controlled trial, with a 1ratio1 ratio, with two-year follow-up. Patients were aged 70 years or older treated with chemotherapy for solid tumour and at risk of malnutrition (MNA, Mini Nutritional Assessment 17-23.5). Intervention consisted of diet counselling with the aim of achieving an energy intake of 30 kCal/kg body weight/d and 1.2 g protein/kg/d, by face-to-face discussion targeting the main nutritional symptoms, compared to usual care. Interviews were performed 6 times during the chemotherapy sessions for 3 to 6 months. The primary endpoint was 1-year mortality and secondary endpoints were 2-year mortality, toxicities and chemotherapy outcomes. RESULTS: Between April 2007 and March 2010 we randomised 341 patients and 336 were analysed: mean (standard deviation) age of 78.0 y (4.9), 51.2% male, mean MNA 20.2 (2.1). Distribution of cancer types was similar in the two groups; the most frequent were colon (22.4%), lymphoma (14.9%), lung (10.4%), and pancreas (17.0%). Both groups increased their dietary intake, but to a larger extent with intervention (p\textless0.01). At the second visit, the energy target was achieved in 57 (40.4%) patients and the protein target in 66 (46.8%) with the intervention compared respectively to 13 (13.5%) and 20 (20.8%) in the controls. Death occurred during the first year in 143 patients (42.56%), without difference according to the intervention (p = 0.79). No difference in nutritional status changes was found. Response to chemotherapy was also similar between the groups. CONCLUSION: Early dietary counselling was efficient in increasing intake but had no beneficial effect on mortality or secondary outcomes. Cancer cachexia antianabolism may explain this lack of effect. TRIAL REGISTRATION: ClinicalTrials.gov NCT00459589.

Summary Background Early chemotherapy might improve the overall outcomes of patients with metastatic non-castrate (ie, hormone-sensitive) prostate cancer. We investigated the effects of the addition of docetaxel to androgen-deprivation therapy (ADT) for patients with metastatic non-castrate prostate cancer. Methods In this randomised, open-label, phase 3 study, we enrolled patients in 29 centres in France and one in Belgium. Eligible patients were older than 18 years and had histologically confirmed adenocarcinoma of the prostate and radiologically proven metastatic disease; a Karnofsky score of at least 70%; a life expectancy of at least 3 months; and adequate hepatic, haematological, and renal function. They were randomly assigned to receive to ADT (orchiectomy or luteinising hormone-releasing hormone agonists, alone or combined with non-steroidal antiandrogens) alone or in combination with docetaxel (75 mg/m 2 intravenously on the first day of each 21-day cycle; up to nine cycles). Patients were randomised in a 1:1 ratio, with dynamic minimisation to minimise imbalances in previous systemic treatment with ADT, chemotherapy for local disease or isolated rising concentration of serum prostate-specific antigen, and Glass risk groups. Patients, physicians, and data analysts were not masked to treatment allocation. The primary endpoint was overall survival. Efficacy analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00104715. Findings Between Oct 18, 2004, and Dec 31, 2008, 192 patients were randomly allocated to receive ADT plus docetaxel and 193 to receive ADT alone. Median follow-up was 50 months (IQR 39–63). Median overall survival was 58·9 months (95% CI 50·8–69·1) in the group given ADT plus docetaxel and 54·2 months (42·2–not reached) in that given ADT alone (hazard ratio 1·01, 95% CI 0·75–1·36). 72 serious adverse events were reported in the group given ADT plus docetaxel, of which the most frequent were neutropenia (40 [21%]), febrile neutropenia (six [3%]), abnormal liver function tests (three [2%]), and neutropenia with infection (two [1%]). Four treatment-related deaths occurred in the ADT plus docetaxel group (two of which were neutropenia-related), after which the data monitoring committee recommended treatment with granulocyte colony-stimulating factor. After this recommendation, no further treatment-related deaths occurred. No serious adverse events were reported in the ADT alone group. Interpretation Docetaxel should not be used as part of first-line treatment for patients with non-castrate metastatic prostate cancer. Funding French Health Ministry and Institut National du Cancer (PHRC), Sanofi-Aventis, AstraZeneca, and Amgen.

e15009Background: Recent studies showed improvement of patients outcomes with addition of aflibercept to FOLFIRI as second-line therapy for metastatic colorectal cancer (mCRC). The addition of afli...

633 Background: The IDEA international collaboration was established to prospectively combine/analyze data from six randomized trials to assess whether a 3-month course of oxaliplatin/fluoropyrimidines-based adjuvant chemotherapy (CT) is non-inferior to the 6-month current standard treatment in stage III colon cancer (CC). The primary endpoint of IDEA was 3-year disease-free survival. The accrual goal for the French IDEA study was 2,000 patients. Methods: French IDEA randomized patients with stage III CC between 3 months (arm A) and 6 months (arm B) of adjuvant CT with modified (m) FOLFOX6 or XELOX (depending on physician/patient choice). Oxaliplatin was stopped in case of persistent neuropathy grade ≥2 with fluoropyrimidines continuation for the planned duration. Toxicity was graded during treatment and follow-up using NCI-CTCAE v3.0. Results: From May 2009 to May 2014, 2,023 patients were randomized in 129 French centers either to arm A (n=1009, 49.9%) or to arm B (n=1014, 50.1%). 2012 (99.5%) patients had stage III disease (N1: 75%; N2: 25%) and 11 patients had stage II (n=2) or stage IV disease (n=9). Median age was 64 years (18-85). 89.4% of patients received mFOLFOX6, 10.1% of patients received XELOX, and 0.5% of patients did not receive any study treatment. Overall, 94.1% and 77.5% of patients completed 3 months (arm A) and 6 months (arm B) of CT, respectively. Median oxaliplatin dose was 500 mg/m2 in arm A and 747 mg/m2in arm B. Toxicity profiles depended on the FU backbone with more grade 3/4 neutropenia on mFOLFOX6 (15.0% vs 6.5%) and more grade 3/4 diarrhea (4.7% vs 8.1%) on XELOX. Grade 2/3-4 peripheral neuropathy was less common in arm A than in arm B (23.2/6% vs 37.9/20.4%). Grade 2/3-4 residual neuropathy for patients with a follow-up of at least 3 years (n=811, median follow-up of 3.91 years) was 2.3/0.5% in arm A vs 3.9/ 2.4% in arm B. At 6 months after randomization, mortality rate was 0.7% (n=7) on arm A and 0.5% (n=5) on arm B. Median follow-up is 2.74 years for the whole population. Conclusions: Both mFOLFOX6 and XELOX were safe. Peripheral neuropathy was lower in arm A than in arm B. Clinical trial information: 2009-010384-16.

3567 Background: VEGF inhibition with (ziv-)aflibercept, a recombinant human fusion protein, in combination with FU/irinotecan improves patient outcomes (overall survival (OS), progression-free sur...

9538 Background: Predicting major adverse events such as functional decline during chemotherapy is an important issue in geriatric oncology. Recent studies have shown that different parts of compre...

325 Background: Our aim was to investigate outcome of patients (pts) treated with AC or NC for organ-confined UC, or with NC for clinical lymph node involvement (cN+). Methods: We retrospectively analyzed 482 pts treated in 22 French hospitals between 2000 and 2013 in 3 settings: 226 pts with radical cystectomy (RC) and AC (AC group), 193 cN0 (NC group), and 63 cN+ (cN+ group) pts received NC before a planned RC for cT2-T4, M0 UC. The primary outcome was overall survival (OS). Cancer-related survival (CRS) was also evaluated. Multivariate Cox proportional hazards regression was used to estimate adjusted hazard ratios with 95% confidence interval. Results: Median age was 62, 61.7, and 62.1 in AC, NC, and cN+, respectively. Median time between diagnosis and first treatment (RC or NC) was 2.1, 1.4 and 1.6 months, respectively (p

Aim: REG is a multi-kinase inhibitor with survival benefits in pts with pretreated mCRC, as demonstrated in the phase III CORRECT study. As a result, REG has been made available for medical practice use in the US, and in the EU. However, prescribing conditions in the real-life setting are known to be less stringent than selection criteria in clinical trials. The REgorafeniB in mEtastatic Colorectal cancer: a French Compassionate progrAm (REBECCA) is an ambispective cohort study designed to elucidate safety and effectiveness outcomes associated with REG as used in clinical practice for mCRC refractory to all available therapies. Methods: Pts were identified from the database of the French ATU (Temporary Authorization for Use), approved by the French Health Authorities to provide early access to innovative, not yet approved medicinal products such as REG. Baseline patient and tumor characteristics, REG dosing and dose-intensity, REG-related adverse events, pre- and post REG treatments, predictors of events, and effectiveness data (PFS, OS) were collected from pts who agreed, and whom physicians accepted to collaborate to the REBECCA study which had OS estimate as a primary objective. Results: 1178 pts met the ATU criteria, of whom 1119 started on REG. 681/1178 (58%) were male. Median age was 64 years (range 25-92). ECOG PS was 0 (31%), 1 (59%), and ≥ 2 (10%). Median time since diagnosis of the metastatic disease was 2.7 years. KRAS mutation was documented in 604/1178 (51%) of pts. Metastases were predominantly located in the liver (76%) and lungs (62%). The starting dose of REG was 160 mg/day in 89.7% of pts. Of the 1178 pts who met the ATU criteria, 787 pts treated by 283 physicians were included in the REBECCA study. Analyses in these patients are in progress. Conclusions: Apart from a baseline PS > 1 in 10% of the pts, the patterns of pts included in the ATU seem to be comparable to those of pts included in the phase III CORRECT study. REBECCA, which is the largest cohort study of REG in mCRC pts ever reported, will provide valuable insights in the therapeutic benefit of this new compound in the real-life setting. Full results of this study will be presented at the meeting. Disclosure: A. Adenis: Bayer (advisory board, research funding). All other authors have declared no conflicts of interest.

Background: The molecular apocrine breast cancer subset has recently been identified. These tumours are estrogen receptor (ER) negative but are characterised by the expression of many genes expressed by ER-positive luminal tumours and, interestingly, are androgen receptor (AR) positive. One third of these tumours are HER2-negative. Abiraterone acetate (AA) is a novel, selective, irreversible, and potent inhibitor of CYP17 enzymatic activity that reduces testosterone levels in the blood to undetectable range. Trial design: We are conducting an uncontrolled, open-label, prospective, multicentric, phase II trial to evaluate the clinical activity of AA in patients with molecular apocrine inoperable locally advanced or metastatic breast cancer. Before inclusion, tumour samples (primary or metastatic) from patients presenting with a triple negative cancer are screened centrally for confirmation of ER/PgR/HER2 negativity and assessment of AR positivity. Additionally patients could be chemotherapy naive or have received any number of lines of chemotherapy with measurable or non-measurable disease. Patients receive AA 1,000 mg and prednisone 10 mg daily until progression or unacceptable toxicity. The primary endpoint is the clinical benefit rate (CR + PR + SD ≥ 24 weeks). Secondary objectives include objective response rate, duration of response, overall survival, progression-free survival and safety. The translational research study focuses on identifying AA response biomarkers as well as improving the molecular definition of apocrine breast cancer, and describing the variation of circulating tumour cells levels. The target accrual is 31 patients. This is a single stage design to discriminate between a 15% and 35% clinical benefit (power 80%, Alpha 5%). As of April 2014, 28 French centers are open for enrolment (first site opened since June 2013). 18 centers have registered 59 patients. Of 55 centrally reviewed tumours, 25 (45%) were tested as ER/PgR/HER2 negative and AR positive leading to the inclusion of 19 patients for now. Disclosure: All authors have declared no conflicts of interest.

Aim: VEGF or EGFR targeted monoclonal antibodies with chemotherapy demonstrated clinical activity in metastatic colorectal cancer (mCRC). Yet, combining these monoclonal antibodies in mCRC achieved adverse outcomes. However, erlotinib (E), an EGFR tyrosine kinase inhibitor, combined with bevacizumab (B) as maintenance (m) therapy after B-based induction therapy (IT) improved progression-free survival (PFS) (Tournigand, ASCO 2012). We report here the final results of the DREAM study. Methods: DREAM is a phase III trial in patients with unresectable mCRC. Pts without progression or surgery after a B-based IT were randomised to B (7.5 mg/kg q3w) or B (same dose) plus E (150 mg/d) as maintenance therapy until progression after stratification by centre, baseline ECOG status, ALP, LDH, induction chemotherapy (XELOX2-B vs mFOLFOX7-B or FOLFIRI-B), KRAS status, age, number of metastatic sites and tumour response (RR). Primary endpoint was mPFS from randomisation. Secondary endpoints were overall survival (OS), PFS from registration (r), response according to KRAS status, adverse events, curative resection, chemotherapy-free interval (CFI), and HR-QoL. Results: Among 701 registered pts, 452 were randomised for maintenance (B, 228; BE, 224). Median follow-up was 50 months. B arm vs BE arm, medians were: mPFS 4.9 vs 5.9 months (HR 0.77, CI 0.62-0.94; p = 0.012), rPFS 9.3 vs 10.2 months (HR 0.76, 95%CI 0.63-0.93; p = 0.007), mOS 22.0 vs 25.0 months (HR 0.80, CI 0.63-0.98; p = 0.034), rOS 26.9 vs 30.5 months (HR 0.80, CI 0.64-0.99; p = 0.040). All subgroups, including KRAS, had a benefit in OS. RR from baseline maintenance were B vs BE arm: all patients 11.5% vs 22.5% (OR 0.45, CI 0.25-0.79; p = 0.003), KRAS WT 15.4% vs 24% (OR 0.58, CI 0.27-1.19; p = 0.133), KRAS mut 8.3% vs 19.7% (OR 0.37, CI 0.12-1.04; p = 0.041). Patients in the B arm vs BE arm experienced less grade 3/4 diarrhea (0.9% vs 9.3%) and skin rash (0% vs 21.4%). Median time on therapy was 110 days in arm BE. Conclusions: Combination of erlotinib and bevacizumab as maintenance therapy significantly prolonged PFS and OS in patients with unresectable mCRC. The combination of anti-VEGF mab and EGFR tyrosine kinase inhibitor is active, even in mutated KRAS patients. Disclosure: B. Chibaudel: Roche, Sanofi; C. Tournigand: Roche, Sanofi; F. Bonnetain: Roche, Nestle, Merck; T. Andre: Roche; A. De Gramont: Roche, Sanofi. All other authors have declared no conflicts of interest.

4550 Background: The benefit of NC on survival in UC has been shown with SD and is most evident in patients (pts) who achieve a pathological complete response (ypT0). In the last decade, physicians...