TC Arm Research Articles

The Comparative Safety of Epirubicin and Cyclophosphamide versus Docetaxel and Cyclophosphamide in Lymph Node-Negative, HR-Positive, HER2-Negative Breast Cancer (ELEGANT): A Randomized Trial.

Simple SummaryAnthracycline and taxane-based chemotherapy are the cornerstone of adjuvant therapy for early breast cancer. In recent years, several trials explored the efficacy of the anthracycline-free regimens, especially for HER2-negative breast cancer patients, which turned out to be a feasible alternative. However, there is no comparison between epirubicin and cyclophosphamide versus docetaxel and cyclophosphamide about their safety and efficacy to date. ELEGANT is the first phase III randomized trial comparing the safety and efficacy of EC versus TC, and it reports comprehensive safety profiles of both regimens with a primary endpoint of grade 3 to 4 neutropenia rate.Background: In adjuvant settings, epirubicin and cyclophosphamide (EC) and docetaxel and cyclophosphamide (TC) are both optional chemotherapy regimens for lymph node-negative, hormone receptor (HR)-positive, human epidermal receptor 2 (HER2)-negative breast cancer patients. Neutropenia is one of the most common adverse events (AEs) of these regimens. The rate of grade 3–4 neutropenia varies in different studies, and direct comparisons of safety profiles between EC and TC are lacking. Method: ELEGANT (NCT02549677) is a prospective, randomized, open-label, noninferior hematological safety trial. Eligible patients with lymph node-negative HR+/HER2-tumors (1:1) were randomly assigned to received four cycles of EC (90/600 mg/m2) or TC (75/600 mg/m2) every three weeks as adjuvant chemotherapy. The primary endpoint was the incidence of grade 3 or 4 neutropenia defined by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 on an intention-to-treat basis. Noninferiority was defined as an upper 95% CI less than a noninferiority margin of 15%. Results: In the intention-to-treat population, 140 and 135 patients were randomized into the EC and TC arms, respectively. For the primary endpoint, the rate of grade 3 or 4 neutropenia is 50.71% (95% CI: 42.18%, 59.21%) in the EC arm and 48.15% (95% CI: 39.53%, 56.87%) in the TC arm (95%CI risk difference: −0.100, 0.151), showing the noninferiority of the EC arm. For secondary endpoints, the rate of all-grade anemia is higher in the EC arm (EC 42.86% versus TC 22.96%, p = 0.0007), and more patients suffer from nausea/vomiting, hair loss, and nail changes (p < 0.01) in the EC arm. No statistically different disease-free survival was observed between the two arms (p = 0.13). Conclusion: EC is not inferior to TC in the rate of grade 3 or 4 neutropenia, but more other AEs were observed in the EC group.

A comparison of two chemotherapy regimens in advanced, recurrent, or metastatic salivary gland carcinoma.

The efficacy of chemotherapy in locally advanced, recurrent, and metastatic salivary gland carcinomas (LA-R/M SGCs) is still undefined. We aimed to compare the efficacy of two chemotherapy regimens in LA-R/M SGC. This prospective study compared paclitaxel (Taxol) plus carboplatin (TC) versus cyclophosphamide, doxorubicin, plus cisplatin (CAP) regimen in terms of overall response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), and overall survival (OS). Between October 2011 and April 2019, 48 patients with LA-R/M SGCs were recruited. The ORRs of first-line TC and CAP regimens were 54.2% and 36.3%, respectively (P = 0.57). The ORRs in recurrent and de novo metastatic patients were 50.0% and 37.5% for TC and CAP, respectively (P = 0.26). The median PFS of TC and CAP arms were 10.2 and 11.9 months, respectively (P = 0.91). In the subanalysis, patients with adenoid cystic carcinoma (ACC) had longer PFS in the TC arm (14.5 vs. 8.2 months, P = 0.03), irrespective of the tumor grade (low grade: 16.3 vs. 8.9 months, high grade: 11.7 vs. 4.5 months; P = 0.03). The median OS rates were 45.5 and 19.5 months for TC and CAP groups, respectively (P = 0.71). For patients with LA-R/M SGC, there was no significant difference between first-line TC and CAP in terms of ORR, PFS, and OS.

The efficacy and safety of apatinib combined with paclitaxel and carboplatin dose-dense regimen in neoadjuvant therapy for locally advanced triple-negative breast cancer.

e12602 Background: Triple negative breast cancer (TNBC) has the traits of early onset, high malignancy and no effective molecular targets to act on, neoadjuvant chemotherapy is recommended as the preferred treatment for locally advanced TNBC with highly recurrence risk. The addition of platinum-based agents to conventional taxanes regimens in locally advanced TNBC can significantly improve pathological complete response (pCR) rate. Anti-angiogenic drugs are currently one of the few targeted therapies that have achieved efficacy in TNBC. Apatinib, an inhibitor of VEGFR2, shows significant antitumor activity in the patients with breast cancer. Methods: Pathologically confirmed TNBC patients with clinical stage I-IIIC (per AJCC 8th ed) with no previous surgery or radio-chemotherapy treatment were enrolled in our center from September 2018 to June 2020. Enrolled patients received 4-8 neoadjuvant treatment cycles of apatinib 250mg per day + paclitaxel 175mg/m2 d1 + carboplatin AUC = 4 d2 q14d (Apa+TC), followed by sequential surgery. Enrolled patients who underwent surgery were matched with TNBC patients received paclitaxel and carboplatin intense regimen (TC) contemporarily in our center by propensity score matching (PSM). pCR in breast and axilla (ie. ypT0/Tis ypN0) was the primary endpoint. Objective response rate (ORR), disease control rate (DCR), event-free survival (EFS), overall survival (OS) and adverse events (AEs) are secondary endpoints. Results: 25 locally advanced TNBC patients were enrolled for neoadjuvant therapy of Apa+TC. In radiological evaluation, 2 patients achieved CR, 20 patients achieved PR, 3 patients achieved SD, which indicated an ORR of 88% and a DCR of 100%. 23 of 25 enrolled patients underwent surgery, with a pCR rate of 60.87% (95%CI: 38.54%-80.29%). 69 patients who were treated by TC before surgery were matched by PSM based on baseline stage T and stage N features. A significant higher pCR rate was achieved in Apa+TC arm compared with TC alone (60.87% vs. 30.43%, respectively, P = 0.009). Similar incidence of AEs was observed between two arms. The main AEs were hematologic toxicities fatigue, digestive canal symptoms, transaminase elevation and peripheral neurotoxicity in Apa+TC arm. Grade III-IV AEs included granulocytopia (14/25), thrombocytopenia (4/25), anaemia (3/25), fatigue (1/25), hypertension (1/25) and arrhythmia (1/25). Meanwhile, apatinib-related AEs, including hypertension, proteinuria, and hand-and-foot syndrome, were mild. Due to the limited time, the survival follow-up is still in progress. Conclusions: Apatinib combined with paclitaxel and carboplatin intensive regimen achieved a better efficacy and manageable adverse events in neoadjuvant chemotherapy for locally advanced TNBC, which might be a promising strategy in the treatment of locally advanced TNBC. Clinical trial information: NCT03735082.

Relationship between Complete Remission and Overall Survival in Acute Myeloid Leukemia: A Report from Daco-016 and Daco-017

The correlation between complete remission (CR) and overall survival (OS) is not well defined for patients with AML who are not eligible for intensive chemotherapy (ICT). With the introduction of hypomethylating agents (HMAs), outcomes have improved compared to low-dose cytarabine or best supportive care, however, there is a need to understand whether patients who achieve a CR following treatment with HMAs experience a longer OS compared to those patients who don't achieve a CR. This retrospective analysis of CR and OS is based on data from two clinical trials of decitabine, DACO-0161 and DACO-0172. The dose schedule of decitabine in both studies was 20 mg/m2 intravenously for 5 consecutive days of continuous 4-week cycles. In DACO-016, the control arm was Treatment Choice (TC; supportive care or cytarabine 20 mg/m2 per day as a subcutaneous injection for 10 consecutive days every 4 weeks). DACO-017 was a single arm study. Morphologic CR was based on the modified 2003 International Working Group criteria. OS was measured from the date of randomization (N=485) in DACO-016 and the date of starting decitabine treatment (N=55) in DACO-017, with patients last known to be alive censored at the last date of contact. OS stratified by CR was estimated using the Kaplan-Meier method and tested using the log-rank test. In DACO-016, 15.7% (N=38) of patients treated with decitabine achieved CR. The median OS for decitabine treated patients who achieved a CR was 19.1 months (95% confidence interval (CI): 15.2-24.2). 97.4% of CRs (N=37) occurred at or after the fourth cycle of decitabine. The median OS for patients who did not achieve a CR with decitabine was 5.7 months (CI: 4.6-7.1) (Figure 1). In contrast, only 7.4% (N=18) of patients treated with TC achieved a CR. In the TC arm, the median OS for patients who achieved a CR was 25.0 months (CI: 16.3-37.0) and 4.5 months (CI: 3.8-5.5) for patients who did not achieve a CR. In DACO-017, the median OS for patients who achieved a CR was 21.6 months (CI: 7.1-24.7). For patients who did not achieve a CR, the median OS was 6.1 months (CI: 3.1-8.1). The median time to CR for decitabine treated patients was 4.6 months. Both studies showed that the median OS of patients who achieved a CR was more than twice that of patients who did not achieve a CR. This analysis demonstrates the prognostic value of CR in relation to OS in patients with AML regardless of treatment and thus the importance of treating patients with decitabine for a minimum of 4 cycles to before evaluating response to treatment. While CR has been shown to be an imperfect surrogate for OS, in this analysis of patients with AML who were ineligible for ICT, achieving a CR remains associated with improved OS benefits vs. not achieving a CR.

THU0370 CLUSTER-RANDOMIZED PRAGMATIC CLINICAL TRIAL EVALUATING THE POTENTIAL BENEFIT OF A TIGHT-CONTROL AND TREAT-TO-TARGET STRATEGY IN AXIAL SPONDYLOARTHRITIS: THE RESULTS OF THE TICOSPA TRIAL.

Background:Current recommendations for axial spondyloarthritis (axSpA) management include tight control and treat-to-target (TC) strategies, but no study has evaluated its potential benefitObjectives:To evaluate the benefit of TC strategies in comparison to usual care (UC) in patients with axSpA.Methods:Study design:Pragmatic, prospective, cluster-randomized controlled (2 arms), one-year trial (NCT03043846).Centers: 18 axSpA expert centers randomly allocated (1:1) to the treatment arm: TC vs. UC.Patients: axSpA diagnosis and ASAS criteria, non-optimally treated with NSAIDs, bDMARD-naïve, and ASDAS &gt; 2.1 at inclusion.Study treatment:a) TC arm: the strategy was pre-specified by the scientific committee based on current axSpA recommendations and aiming at a target (ASDAS &lt;2.1); visits every 4w;b) UC arm:treatment decisions were at the rheumatologist’s discretion with visits every 12w.Outcomes:the % of patients with a significant (&gt;30%) improvement in the ASAS-HI score over one-year follow-up was the main outcome. Other outcomes (disease activity, quality of life, treatment, …) over follow-up were evaluated (Table 1). The number/type of adverse events were collected.Statistical analysis: this was an intention-to-treat analysis. To take into account the cluster-randomization design, for all outcomes, two models were performed: first a two-level mixed model with 2 random effects was used to estimate the % of responders/the change of the outcome over follow-up (i.e. mod1); in a second step, the imbalanced variables observed at baseline were included in the model (i.e.mod2). Cost-effectiveness was assessed by estimating the (baseline- and cluster-adjusted) incremental cost per quality-adjusted life-year (QALY) gained for TC vs. UC.Estimated outcomes at week 48Cluster-adjusted (mod1)Cluster and imbalance-adjusted (mod2)TCUCASDAS LDA*76.5%59.5%&lt;0.010.03ASDAS ID25.9%18.7%--ASDAS CII61.2%46.0%&lt;0.010.02ASDAS MI16.5%14.9%--ASAS4052.3%34.7%&lt;0.010.01ASAS2094.9%85.9%&lt;0.010.03BASDAI 5079.0%43.8%0.010.03Physician Global (0-10)2.0 (0.2)1.8 (0.2)--CRP (mg/L)3.9(1.4)3.5 (1.5)--BASG (0-10)2.6 (0.5)3.4 (0.5)0.09-BASFI (0-10)1.7(0.5)2.4 (0.5)--ASAS HI SMD47.3%36.1%--EQ5D0.7(0.1)0.8(0.1)0.02-ASAS-NSAID score1.5(2.2)- 4.9 (2.9)--Results:160 patients were included (80 in TC and 80 in UC). Mean age was 37.9(11.0) years with a disease duration of 3.7(6.2) years, 51.2% were males. A radiographic damage of the SI-joints, a (ever) positive MRI sacroiliitis and HLA-B27+ were seen in 46.9%, 81.9% and 75.0% patients respectively. Mean ASDAS at inclusion was 3.0 (0.7) and mean ASASHI was 8.6 (3.7). 72 patients per group attended the one-year visit. Although 47.3% vs. 36.1% patients in the TC and UC arms achieved a significant improvement in ASASHI at the one-year visit, the difference was not statistically significant, with either model. Across all other outcomes a trend was observed in favor of the TC arm (Table 1). The number of bDMARDs was significantly higher in TC arm (56.2% vs. 27.2%). The number of infections was comparable in both groups (15 vs. 16 in the TC and UC, respectively), with only 2 severe infections occurring in the UC arm. From a societal perspective, TC resulted in an additional 0.04 QALY and saved €265 when compared to UC and a 67% probability of being cost-effective at a cost-effectiveness threshold of €20,000 per QALY.Conclusion:In this setting of SpA expert centers, UC resulted in a good outcome in a substantial number of patients but the TC was not superior for the primary outcome despite a greater number of bDMARDs prescription. Nevertheless, a general trend in favor of the tight control was observed, with a comparable safety profile and was found to be favorable from a societal health economic perspective.Acknowledgments:this trial has been conducted thanks to an unrestricted grant from UCBDisclosure of Interests:Anna Moltó Grant/research support from: Pfizer, UCB, Consultant of: Abbvie, BMS, MSD, Novartis, Pfizer, UCB, Clementina López-Medina: None declared, Filip van den Bosch Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Annelies Boonen Grant/research support from: AbbVie, Consultant of: Galapagos, Lilly (all paid to the department), Casper Webers: None declared, Emmanuelle Dernis Speakers bureau: Lilly, Novartis, Floris A. van Gaalen: None declared, Martin SOUBRIER: None declared, Pascal Claudepierre Speakers bureau: Janssen, Novartis, Lilly, Athan Baillet Consultant of: Athan BAILLET has received honorarium fees from Abbvie for his participation as the coordinator of the systematic literature review, Mirian Starmans-Kool: None declared, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, Maxime Dougados Grant/research support from: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Speakers bureau: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma

Abstract P2-10-03: Genomic markers but not molecular subtypes provide prognostic impact and predict anthracycline efficacy in early triple-negative breast cancer: Results from the prospective WSG PlanB trial

Abstract Background: Optimal treatment, particularly use of anthracyclines in aggressive triple-negative breast cancer (TNBC), is still a controversial issue in early BC management. However, TNBC exhibits substantial molecular heterogeneity: for example, the immune phenotype seems to be associated with better outcome. An important clinical issue in early TNBC is to quantify the impact of subtypes as well as individual genes on survival and especially on anthracycline benefit. Methods: In PlanB, patients with ER and PR&amp;lt;1% (local or central lab), HER2- EBC were treated by TC (6 cycles Docetaxel/Cyclophosphamide) or EC-Doc (4xEpirubicin/Cyclophosphamideà4xDocetaxel) (overall n=2449, HER2-). RNA isolation was successfully performed in n=402/449 patients with available follow-up. Gene (n=119) expression data by Nanostring® platform were entered into univariate and multivariate Cox models for disease-free survival (DFS) to identify genes (and combinations) with potential prognostic and/or predictive impact. Median follow-up was 60 months. Results: RNA expression results were available in n=394 (203 TC vs. 191 EC-Doc): PAM-50 subtype: basal-like 82%; HER2-enriched 7%; luminal (A or B) 3.5%; normal-like 7.4%. Median age was 54; 78% were node-negative. In patients with “discordant” tumors (HR positive by local or central assessment), 76% were still basal-like, compared to 86% in “concordant” TNBC. Of 27 patients with HER2-enriched subtype, HER2 status was positive by central assessment in only five cases (18%). Within this TN cohort, 5y DFS was similar in TC (83%) and EC-Doc (79%) arms; positive nodal status and tumor size &amp;gt;2 cm were (unfavorable) clinical-pathological prognostic markers. Prognostic or predictive impacts of molecular subtype, risk of recurrence subgroups, or proliferation indices were not seen. Twelve genes (incl. CD8, EGFR, GPR160, SPINT2) showed potential multivariate prognostic impact by entering the “forwards stepwise” multivariate Cox model for DFS. The upper half of patients according to the resulting “twelve-gene signature” had well over 90% 5y-DFS, whereas the lowest quartile had under 60% 5-y DFS. Several genes (incl. ERBB2, FOXC1) showed potential for a predictive impact regarding TC vs. EC-Doc by interaction analysis. Further details and perspectives for testing the robustness of these potential impacts will be presented at the meeting. Conclusions To our knowledge, these are the first results from a prospective, adjuvant taxane-based trial regarding molecular predictors of anthracycline efficacy and PAM-50-based prognostic factors in early TNBC. ERBB2 expression, but not HER2-enriched subtype, was predictive for A-benefit in HER2-negative BC. Molecular heterogeneity of TNBC beyond basal-like vs. non-basal-like subtype is clinically relevant and should be considered for patient stratification in ongoing trials with combination therapy. The identified prognostic gene signature should be validated in the WSG-ADAPT-TN and other TNBC trials. Citation Format: Gluz O, Liedtke C, Prat A, Christgen M, Gebauer D, Kates R, Pelz E, Clemens M, Warm M, Aktas B, Kuemmel S, Pare L, Krabisch P, Kreipe HH, Wuerstlein R, Nitz U, Harbeck N. Genomic markers but not molecular subtypes provide prognostic impact and predict anthracycline efficacy in early triple-negative breast cancer: Results from the prospective WSG PlanB trial [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-10-03.

Prospective WSG phase III PlanB trial: Final analysis of adjuvant 4xEC→4x doc vs. 6x docetaxel/cyclophosphamide in patients with high clinical risk and intermediate-to-high genomic risk HER2-negative, early breast cancer.

504 Background: Optimal chemotherapy in HER2-negative, particularly HR-positive, early breast cancer (EBC), especially the survival impact of anthracyclines, is still a matter of debate. Retrospective analyses saw most benefit of 6xCEF vs. 6xCMF in HER2+ EBC. Prospective trials have shown conflicting results; no predictive molecular factors have been validated so far, particularly for HR+ EBC. The WSG PlanB trial is the first trial that randomized only patients with high clinical risk or with Recurrence Score &gt;11 in the HR+/HER2- subgroup (pN0-1). Patients with RS&lt;11 (pN0-1) had an excellent prognosis (five-year DFS of 94%) with endocrine therapy alone (Gluz et al. ASCO 2016). Methods: The WSG PlanB trial was originally planned as a non-inferiority study for comparison of 6 cycles of anthracycline-free TC (Arm A) vs. standard anthracycline-taxane based chemotherapy (4xEC→4xDoc) (Arm B) in patients with high-risk pN0 (T2-4, G2-3, &lt;35 years, or high uPA/PAI-1) or pN+ HER2- EBC. Following an early amendment, Oncotype DX was performed in all HR+ tumors, and omission of chemotherapy (CT) was recommended in RS≤11 HR+ pN0-1 disease. Primary endpoint was DFS, defined as time to any recurrence, secondary cancer or death. Final analysis for the CT randomization was planned after completed 5-year follow-up in all patients. Results: From 2009 to 2011, PlanB enrolled 3198 patients (n=3073 with central pathology review). In 348 patients (15.3%), CT was omitted based on RS≤11. 2449 patients were randomized to 6xTC (n=1222) and 4xEC→4xDoc (n=1227). Within this cohort, 41% were pN+, 42% had G3 tumors and 18% HR-negative tumors by central pathology. After median follow-up of 61 months, very similar five-year DFS of 89.9% [88.1%-91.7%] vs. 90.2% [88.4%-92.0%] and five-year OS of 94.7% [93.4%-96.1%] vs. 94.6% [93.2%-96.0%] were observed in Arms A vs. B. Five treatment-related deaths were observed in Arm A (TC) vs. one in Arm B (EC-Doc) (0.4% vs. 0.1%), despite a trend to more SAE’s in Arm B vs. Arm A (n=397 vs. 358). Although recurrence score is a strong prognostic factor, it was not predictive for anthracycline efficacy; no efficacy differences between the study arms were observed in (locally) triple-negative patients or in those with &gt;4 involved lymph nodes, despite the prognostic impact of these factors. Conclusion: In the WSG PlanB trial, patients with early HER2-negative BC seem to be sufficiently treated by six cycles of docetaxel/cyclophosphamide compared to four cycles of EC followed by four cycles of docetaxel -- no efficacy differences are evident in high-risk subgroups defined by triple-negative status, nodal status, or high Recurrence Score. Further prospective studies are urgently needed before final conclusions for impact of anthracyclines in HER2-negative BC can be drawn. Clinical trial information: NCT01049425.

Dose-dense FEC followed by docetaxel versus docetaxel plus cyclophosphamide as adjuvant chemotherapy in women with HER2-negative, axillary lymph node-positive early breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG)

Sequential administration of anthracycline and taxane is the current standard of care adjuvant regimen for node-positive early breast cancer. Due to long-term toxicity concerns, anthracycline-free regimens have been developed. We compared a sequential dose-dense anthracycline and taxane regimen with the anthracycline-free regimen of docetaxel and cyclophosphamide. In this randomized, non-inferiority, phase III trial, women with HER2-negative invasive breast cancer and at least one positive axillary lymph node were randomized to receive either epirubicin (75 mg/m(2)), 5-fluorouracil (500 mg/m(2)) and cyclophosphamide (500 mg/m(2)) every 2 weeks for four cycles, followed by four cycles of docetaxel (75 mg/m(2)) every 2 weeks with prophylactic G-CSF support (FEC → D) or docetaxel (75 mg/m(2)) and cyclophosphamide (600 mg/m(2)) every 21 days for six cycles (TC). The primary end point of the study was the 3-year disease-free survival (DFS) rate. Six hundred and fifty women were randomized to either FEC → D (n = 326) or TC (n = 324). After a median follow-up of 46 and 47 months, the 3-year DFS rate was 89.5% and 91.1% for the FEC → D and TC arm, respectively (hazard ratio = 1.147, 95% confidence interval 0.716-1.839, P = 0.568). Grade 3-4 neutropenia was higher in the TC arm (32.4% versus 10.5%, P = 0.0001). The incidence of neutropenic fever was low (<1%). Nausea, vomiting, hand-foot syndrome and fatigue (grade 3-4) were more common with FEC → D. Acute cardiotoxicity was rare (1 event in each group). There were no toxic deaths. This trial did not clearly demonstrate that TC is non-inferior to dose-dense FEC → D. However, 3-year DFS rates were excellent in both arms for women with node-positive, HER2-negative early breast cancer. NCT01985724.

Retrospective analysis of the survival benefit of chemotherapy for recurrent or advanced epithelial ovarian carcinoma in patients previously treated with paclitaxel plus platinum-based chemotherapy.

The outcomes of treatment for women with recurrent or advanced epithelial ovarian carcinoma previously treated with pacli- taxel plus platinum-based chemotherapy were analyzed. Retrospective analysis was performed in a total of 65 series of treatments provided for 35 patients with a history of paclitaxel plus platinum-based chemotherapy. The chemotherapy regimens used were classified into the following four types for analysis: conventional paclitaxel plus carboplatin therapy (TC arm), pegylated liposomal doxorubicin-containing regimens (PLD arm), CPT-11-containing regimens (CPT-11 arm), and others. Disease-control rates (DCRs) were compared and subjected to univariate analysis. Progression-free survival (PFS) was determined from the date of the first cycle of each chemotherapy with the Kaplan-Meier method, and comparisons were performed using the log-rank test. DCR was 80%, 71%, and 26% for the TC, PLD, and CPT-l arms, respectively. The median PFS was 286, 372, and 76 days for the TC, PLD, and CPT-11 arms, respectively. There was no discernible difference in PFS between the TC and the PLD arm. In contrast, PFS of the CPT- 11 arm was significantly shorter than that of the TC and PLD arms. In addition, three of seven (42.9%) treatments in the PLD arm maintained a progression-free period for longer than one year, while only one of 25 (4%) treatments in the TC arm maintained a progression-free period for more than one year. The PFS of PLD is similar to that of TC. PLD-containing regimens might have a potential benefit with a higher PFS over one year than the TC regimen.

Abstract P1-14-06: A phase II randomized study with eribulin/cyclophosphamide (ErC) and docetaxel/cyclophosphamide (TC) as neoadjuvant therapy in HER2-negative breast cancer- Final analysis of primary endpoint and correlative analysis results

Abstract Background: Eribulin mesylate (Er) is a non-taxane inhibitor of microtubule growth that results in G2-M cell cycle arrest, disruption of normal mitotic spindles and apoptosis. Er demonstrated an overall survival (OS) but not progression free survival (PFS) advantage in anthracycline and taxane refractory breast cancer pts. This OS rather than PFS benefit has been attributed to Er's potential to suppress new metastases through its effects on the epithelial mesenchymal transition (EMT) pathway, even in the absence of an effect on the primary tumor or established metastases. In this study ErC was compared to TC, a standard regimen for (neo) adjuvant treatment. A companion exploratory analysis examined the EMT markers E-cadherin and vimentin, as well as the endothelial marker CD-31 assessing tumor vasculature. Final assessments of the primary endpoint of pathological complete response (pCR) and results of the correlative studies will be presented. Methods: Women with histologically confirmed invasive HER2-negative (IHC 0-1+ or FISH/SISH negative), cT1-3, cN0-2, M0 (pN3a disease allowed) adenocarcinoma of the breast were eligible. Following a 10 pt lead-in to confirm the safety/feasibility of ErC, pts were randomized 2:1. Arm 1, Er 1.4 mg/m2 IV (Days 1 &amp; 8) and C 600 mg/m2 IV (Day 1); Arm 2, T 75 mg/m2 IV and C 600 mg/m2 IV on Day 1, both regimens administered q 21 days x 6 cycles followed by surgery. Tumor samples were collected at baseline and from residual breast cancer at the time of surgery. Samples were assayed for E-cadherin, vimentin, and CD-31 expression by immunohistochemistry. Results: Enrollment was completed 4/2014 (76 pts); 10 pts in lead-in phase, 66 pts were randomized (Arm 1, 44; Arm 2, 22). In the randomized population, 77% had invasive ductal adenocarcinoma; median tumor size 3.1 cm (range, 0.4-10cm; 29.5% were T3); axillary nodes clinically positive in 52%. 34% of pts were triple negative (TN). 59 pts (89%) underwent surgery after receiving neoadjuvant chemotherapy (NAC) on study. pCR rates were 9% and 18% on the TC and ErC arms respectively. 4/7 pts with pCR on the ErC arm were TN. tumor samples were analyzed from 69 pts (including lead-in pts) for expression of the EMT biomarkers. Of these, 40 pts had paired pre- and post-treatment samples, and 29 pts had either a pre- or post-treatment sample (including 8 pre-treatment samples from pts who achieved pCR). In pre-treatment tumor specimens (61 samples), E-cadherin levels were modest-high in 80%, vimentin expression was seen in 39%, and CD-31 expression observed in 21% of the samples. Analysis of pre- and post-treatment paired specimens and differential effects according to treatment regimen will be presented. Conclusion: The observed pCR rate of 18% with ErC in this HER2- pt population was comparable with other NAC regimens. Correlative evaluation of EMT markers and tumor vascular density with response is ongoing and will be presented. Citation Format: Yardley DA, Chandra P, Hart L, Wright GS, Ward P, Mani A, Shastry M, Finney L, Guo S, DeBusk LM, Hainsworth JD, Burris III HA. A phase II randomized study with eribulin/cyclophosphamide (ErC) and docetaxel/cyclophosphamide (TC) as neoadjuvant therapy in HER2-negative breast cancer- Final analysis of primary endpoint and correlative analysis results. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-14-06.

Decitabine Improves Outcomes in Older Patients with AML and Higher Blast Counts

S192 salvage 31% (9/29), (c) intense first-salvage and less-intense secondsalvage 4% (2/45), (d) less-intense firstand less intense secondsalvage 4% (1/23) (Table 1). Conclusions: Pending evaluation of other covariates (CR1 duration, age, transplant in first CR, cytogenetics etc.), our data suggest that intensity of first-salvage had no significant effect on CR rate with second-salvage therapy. This suggests that the policy of regarding various salvage regimens as identical when limiting number of prior treatments for purposes of study eligibility is reasonable. 225 Decitabine Improves Outcomes in Older Patients with AML and Higher Blast Counts Table 1 Patient Characteristics for Both Arms of DACO-016 Trial Characteristic DAC TC N(%) 127 (47) 144 (53) Median age [years] 73 73 Male sex [%] 56 65 Secondary AML [%] 24 30 t-AML [%] 5 1 BM Blast count Median Blast Percent 55% 55% Pts. with > 30% BM blasts [%] 100 100 Pts. with > 50% BM blasts [%] 57 55 Adverse Cytogenetics [%] 37 33 WBC Median (range) 2.3 (0.3-13.9) 3.2 (0.5-14.8) Pts. with WBC > 15 0 0 ECOG PS (%] 0-1 76 74 2 24 26 1-yr OS 37% 27% Median Relapse-Free Survival (m) 9.5 7.7 30-day mortality [%] 10 6 Grade 3-4 Heme toxicity (%) anemia 33 23 neutropenia 23 20 neutropenic fever 42 25 Thrombocytopenia 34 35 Tapan Kadia, Xavier Thomas, Anna Dmoszynska, Agnieszka Wierzbowska, Mark Minden, Christopher Arthur, Peter De Porre, Liang Xiu, Margaret Doyle, Jacqueline Bussolari, Hagop Kantarjian Leukemia, MD Anderson Cancer Center; Hopital Edouard Herriot; Haematooncology and Bone Marrow Transplantation, Medical University of Lublin; Medical University of Lodz; Princess Margaret Cancer Centre; Royal North Shore Hospital; Janssen; Janssen Research & Development, USA; Janssen-Cilag Ltd Introduction: Hypomethylating agents such as decitabine (DAC) and 5-azacytidine (AZA) have been shown to improve outcomes in older patients with high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) with 20-30% bone marrow (BM) blasts. The AML-001 trial compared AZA vs. conventional care ([CC]; which included supportive care [SC], intensive chemotherapy [IC], or low-dose cytarabine [LDAC] ) in older patients with AML and BM blasts > 30%. AZA was associated with a trend towards improvement in OS (10.4 vs. 6.5 months, HR1⁄40.84; p1⁄40.083) compared to CC (Dombret, et. al. EHA 2014). Methods: DACO-016 was a multicenter, randomized, phase III trial of DAC vs. treatment choice ([TC]; SC or LDAC) in older patients with AML (Kantarjian, et. al. JCO 2012). In order to have a cohort comparable to the AZA-001 trial, we selected a subset of patients from DACO-016 with BM blast counts >30% and WBC count < 15. We then analyzed the clinical characteristics and outcomes of these patients. The OS data is based on the mature data set of DACO-016 with the clinical cutoff in October 2010, having a median follow-up of 30.7 months. Results: Of the 485 pts on the trial, 271 (56%) met the criteria to be analyzed, 127 (47%) who received DAC and 144 (53%) who had TC. Patient characteristics for both arms are summarized in Table 1. Patients on the DAC arm received a median of 4 cycles (range, 1-33) compared to a median of 2 (1-34) cycles on the TC arm. The CR/CRi rate was 27% for DAC vs. 11% for TC. This was associated with a significantly improved OS for patients receiving DAC (8.6 vs. 4.7 months, HR1⁄40.67; p1⁄40.0033)(Figure 1). This represented an absolute improvement of 3.9 months or a relative improvement of 83% over TC. The relapse-free survival was 9.5 vs. 7.7 months for DAC vs. TC. When censored at the time of subsequent therapy, DAC maintained a Clinical Lymphoma, Myeloma & Leukemia June 2015 significant OS advantage compared to TC (9.3 vs. 5 months, HR 0.69; p1⁄40.011). The 30-day mortality was similar for DAC vs. TC (10% vs. 6%), but DAC was associated with a higher rate of grade 3-4 hematologic toxicity (Table 1). Conclusion: DAC is an effective treatment in older patients with AML and may also improve outcomes in patients with higher BM blast counts.

Simplification to atazanavir/ritonavir+lamivudine in virologically suppressed HIV-infected patients: 24-weeks interim analysis from ATLAS-M trial.

IntroductionWe report interim 24-weeks efficacy data of ATLAS-M trial, a phase IV, multicentre, open-label, randomized study designed to show 48-weeks, non-inferior efficacy (margin of −12%) of treatment simplification to atazanavir/ritonavir (ATV/r)+lamivudine (3TC) versus maintaining 3-drugs ATV/r-based cART.MethodsSubjects on ATV/r+2 NRTIs, without previous treatment failure (TF), with HIV-RNA <50copies/mL for >3 months and CD4>200 cells/mm3 for >6 months were eligible. At baseline, patients were randomized to switch to ATV/r+3TC (arm one) or to maintain the original 3-drug regimen (arm two). Primary endpoint: proportion of patients free of TF at week 48. TF was defined as treatment modification for any reason, including virological failure (VF=two consecutive HIV-RNA>50 copies/mL or a single value >1000 copies/mL). Enrollment of 266 patients was planned.ResultsA total of 266 patients (78% males, median age 44 years, median CD4 603 cells/µL, 79% treated with a tenofovir-containing backbone) were enrolled. At the time of analysis, 24 weeks data were available for 84 and 87 patients in arm one and two, respectively. At baseline, subjects in the two arms did not differ for the main characteristics. At 24 weeks, at the intention to treat analysis the proportion of patients free of TF was 91.7% (95% CI 85.8–97.6) and 85.1% (95% CI 77.6–92.6) in arm one and two, respectively (difference +6.6%, 95% CI −2.9/+16.1). VF was observed in two patients randomized to arm one (one at baseline, before treatment simplification) and one to arm two without resistance mutations. Clinical and laboratory adverse events occurred at similar rates in the two arms. At week 24, patients in arm one showed a greater increase in CD4 (mean change +90 vs +10 cells/µL, p=0.007). A greater increase in total cholesterol (+18 vs −2 mg/dL, p<0.001), HDL (+4 vs +0 mg/dL, p=0.001) and LDL (+12 vs +0 mg/dL, p=0.001) was also observed in arm one without differences in other lipid parameters. Renal function showed a significant improvement in arm one (mean change in eGFR +5 vs −2 mL/min/1.73m2 in arm two, p=0.001). No significant differences in bilirubin levels or other laboratory parameters were observed between the two arms.ConclusionsThis interim analysis suggests a 24-weeks non-inferior efficacy of treatment simplification to ATV/rit+3TC as compared to continuation of ATV/rit +2 NRTI in virologically suppressed patients. Follow-up until 48-weeks is scheduled to confirm these data.

SAT0088 Economic Evaluation of A Tight-Control Treatment Strategy Using an Imaging Device (HANDSCAN) for Monitoring Joint Inflammation in Early Rheumatoid Arthritis

BackgroundNowadays treat-to-target by means of tight-control is generally accepted as the standard treatment principle in early rheumatoid arthritis (RA) (Schoels et.al.). However, this requires frequent (monthly) visits including comprehensive clinical...

Reduction of Toxicity by Reversing the Order of Infusion of Docetaxel and Cyclophosphamide

Background: This retrospective study aimed to determine whether adverse events are more common in docetaxel followed by cyclophosphamide (TC) as compared to the reverse infusion order (rTC). Methods: A retrospective analysis was undertaken at a single institution for 92 consecutive cases treated with TC or rTC for stage I-III breast cancer in a neoadjuvant/adjuvant setting between December 2006 and June 2011. TC was administered during the first 2.5 years and rTC in the latter 2 years. Results: Among the 92 cases, 50 were in the TC arm and 42 in the rTC arm. Fatigue (72.0 vs. 23.8%), edema (48.0 vs. 16.7%), peripheral neuropathy (66.0 vs. 14.3%), myalgia (48.0 vs. 9.5%) and stomatitis (48.0 vs. 16.7%) occurred significantly more often in cases receiving TC compared to rTC, respectively. Conclusion: Nonhematological toxicities are less common in cases receiving rTC in comparison to those receiving TC.

First-line treatment of advanced ovarian cancer with paclitaxel/carboplatin with or without epirubicin (TEC versus TC)—a gynecologic cancer intergroup study of the NSGO, EORTC GCG and NCIC CTG

The addition of anthracyclines to platinum-based chemotherapy may provide benefit in survival in ovarian cancer patients. We evaluated the effect on survival of adding epirubicin to standard carboplatin and paclitaxel. We carried out a prospectively randomized phase III study comparing carboplatin plus paclitaxel (TC; area under the curve 5 and 175 mg/m(2)) with the same combination and epirubicin (TEC; 75 mg/m(2) i.v.). Between March 1999 and August 2001, 887 patients with epithelial ovarian, tubal or peritoneal cancer International Federation of Gynecology and Obstetrics stages IIB-IV were randomized to receive either TC (442 patients) or TEC (445 patients). Median time to progression was 16.4 months in the TEC arm and 16.0 months in the TC arm (hazard ratio 0.99; 95% confidence interval [CI]: 0.9-1.2). Median overall survival time was 42.4 months for the TEC arm and 40.2 for the TC arm (hazard ratio 0.96; 95% CI: 0.8-1.1). Grade 3/4 hematologic toxic effects and most grade 3/4 non-hematologic toxic effects were more frequent in the TEC arm. Accordingly, a quality-of-life analysis showed inferiority of TEC versus TC. The addition of epirubicin to standard carboplatin and paclitaxel treatment did not improve survival in patients with advanced ovarian, tubal or peritoneal cancer.

O3-020 - A Randomized Phase III Trial of Paclitaxel Plus Carboplatin (TC) Versus Paclitaxel Plus Cisplatin (TP) in Stage IVB or Recurrent Cervical Cancer: Japan Clinical Oncology Group Study (JCOG0505)

ABSTRACT Background TC is a less toxic regimen in terms of milder nephropathy, neuropathy and no need of hospitalization. This phase III trial was designed to evaluate the clinical benefits of TC compared with TP which is the current standard chemotherapy for stage IVB or recurrent cervical cancer. Methods Patients with stage IVB or recurrent cervical cancer—not amenable to curative therapy; 0-1 prior platinum; no prior taxanes—were randomized with the minimization method to either TP (T 135 mg/m2 24h d1 + P 50 mg/m2 2h d2) or TC (T 175 mg/m2 3h d1 + C AUC5 1h d1), both for maximum six cycles every 21 days. Primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), toxic effects, and the proportion of non-hospitalization periods (NHP) as a surrogate for QoL. The planned sample size was 250 patients with one-sided a = 5% and at least 70% power to confirm the non-inferiority of TC to TP (threshold hazard ratio [HR] 1.29) in terms of OS. HR is estimated by a stratified Cox regression. Results From February 2006 to November 2009, 253 patients were enrolled. The median follow-up is 17.4 months. 71% of patients of the TP arm and TC arm each received six cycles. Results are as follows: as an alevel for an interim analysis was Conclusions This first randomized, controlled trial comparing carboplatin doublet with cisplatin doublet showed significant non-inferiority of TC in terms of OS. More feasible and less toxic TC can be recommended as the new standard treatment of stage IVB or recurrent cervical cancer. TP TCOS (median) 18.3 months, 17.5 months, HR 0.99 (multiplicity adjusted 90% CI: 0.79–1.25); non-inferiority P = 0.032 PFS (median) HR 1.04 (95% CI: 0.80–1.35) 6.90 months 6.21 months neutropenia G3–4 85.1% 76.4% thrombocytopenia G3–4 3.3% 23.6% febrile neutropenia G3–4 16.0% 7.3% creatinine G2–4 9.8% 4.1% neuropathy (motor) G3–4 0.8% 2.4% neuropathy (sensory) G3–4 0% 4.9% NHP (P

A randomized, phase III trial of paclitaxel plus carboplatin (TC) versus paclitaxel plus cisplatin (TP) in stage IVb, persistent or recurrent cervical cancer: Japan Clinical Oncology Group study (JCOG0505).

5006 Background: TC is a less toxic regimen in terms of milder nephropathy, neuropathy and no need of hospitalization. This multicenter phase III trial was designed to evaluate the clinical benefits of TC compared with TP which is current standard chemotherapy for stage IVB or recurrent cervical cancer. Methods: Patients (pts) with stage IVB or recurrent cervical cancer; not amenable to curative therapy; 0-1 prior platinum; no prior taxanes; were randomized with minimization method to either TP (T 135 mg/m2 24h d1 + P 50 mg/m2 2h d2) or TC (T 175 mg/m2 3h d1 + C AUC5 1h d1), both for maximum 6 cycles every 21 days. Primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), toxicities, and the proportion of non-hospitalization periods (NHP) as a surrogate for QoL. The trial was powered at least 70% to confirm the non-inferiority of TC to TP (threshold hazard ratio [HR] 1.29) in terms of OS, and the planned sample size was 250 pts with one-sided alpha 5%. HR is estimated by a stratified Cox regression. Results: From 2/06 to 11/09, 253 pts were enrolled. 71% pts of TP arm and TC arm each received 6 cycles. Median follow-up is 17.4 mo. Results are as below. As an alpha level for an interim analysis was less than 0.0001, significance level for the final analysis is approximately 5% even after the multiplicity adjustment. Conclusions: This first randomized controlled trial comparing carboplatin doublet with cisplatin doublet showed significant non-inferiority of TC in terms of OS. More feasible and less toxic TC can be recommended as the new standard treatment for stage IVB or recurrent cervical cancer. [Table: see text]

Randomized phase II trial of carboplatin and paclitaxel with or without lonafarnib in first-line treatment of epithelial ovarian cancer stage IIB–IV

ObjectivesThis study evaluates whether a molecular targeted therapy with the farnesyltransferase inhibitor lonafarnib added to standard chemotherapy in first-line treatment of advanced ovarian cancer (OC) could improve progression-free (PFS) and overall survival (OS). Patients and MethodsWe performed a prospective randomized phase II study to compare standard therapy carboplatin (C; AUC 5) and paclitaxel (T; 175mg/m2) in primary advanced OC with or without lonafarnib (L). Lonafarnib was given in a dose of 100mg orally twice a day during chemotherapy and was increased afterwards to 200mg up to six months as a maintenance therapy. Results105 patients were recruited (53 patients were randomized to receive LTC, 52 to TC). Hematologic toxicity was similar in both arms. Grade 3 and 4 non-hematological toxicity, occurred significantly more often with LTC (23% versus 4%, p=0.005) and was associated with a higher dropout rate. PFS and OS were not significantly different among both arms. The LTC arm showed inferiority in the stratum with residual tumor of more than 1cm: median PFS was 11.5months (95% CI: 7.4–14.2) compared with 16.4 (95% CI: 10.3–40.4) for TC (p=0.0141; HR=0.36 (95% CI: 0.15–0.84)) with median OS 20.6months (95% CI: 13.1–31.0) and 43.4months (95% CI: 15.7–) for the TC arm (p=0.012; HR=0.32 (95% CI: 0.13–0.8)). ConclusionThe addition of lonafarnib did not improve PFS or OS. Patients with a residual tumor of more than 1cm had significantly shorter PFS and OS. Incorporation of lonafarnib into future studies for primary therapy of OC is not recommended.

P5-18-09: The Incidence of Febrile Neutropenia in the First Course of Adjuvant Chemotherapy with Docetaxel/Cyclophosphamide with or without Pegfilgrastim.

Abstract Background In our original doxorubicin-cyclophosphamide/docetaxel-cyclophosphamide (AC/TC) adjuvant study (JCO 27: 1177–1183, 2009), we reported an incidence of febrile neutropenia (FN) of 5% (8% in women ≥65 years) with the TC regimen without prophylactic WBC growth factors but with a recommendation for prophylactic antibiotics. There is a paucity of data on the incidence of FN with the TC regimen aside from this clinical trial. Because we have been conducting a randomized adjuvant study of TC compared to other regimens, we used this opportunity to analyze the incidence of FN during the first course of chemotherapy with TC in the first cohort of randomized patients (US Oncology Network study 06090). The prophylactic use of WBC growth factors was at the investigator's discretion. Patients and Methods The study included 1298 patients entered between May 2007 and May 2009. Of these, 649 were included in the TC arm. Median age was 54 years (range 27–71), 75.5% were Caucasian, 561 (86.4%) were in PS 0 at baseline, and about half were node negative. Eight patients did not receive study treatment for various reasons. Among the 641 patients who received TC; 213 (33.3%) received pegfilgrastim, 48 (7.5%) received filgrastim and were not included in this analysis, and 380 (59.2%) patients did not receive either during the first cycle. Thus, this analysis focused on 593 women who did or did not receive prophylactic pegfilgrastim in cycle 1. Results: All patients with a reported adverse event of FN or with a reported AE of fever with some degree of neutropenia (in order to capture all possible cases of FN) during the first cycle of TC were identified [Table 1]. FN and fever + neutropenia occurred in a total of 6 (2.8%) patients who received pegfilgrastim and 36 (9.5%) patients who did not. A comparison of age, race, performance status and stage of disease between these 2 groups revealed that they were similar. The 213 patients who received pegfilgrastim were slightly older (median 56 years, range 27–71) compared to those who did not (median 53 years, range 30–71). During all 6 cycles, 41 patients reported FN, and 30 (73%) of these patients experienced FN during cycle 1. Conclusion: Among 593 women who received TC as adjuvant chemotherapy, the incidence of FN during the first cycle was under 10% whether or not the patients received prophylactic pegfilgrastim. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-18-09.

P5-18-03: First Interim Toxicity Analysis of the Randomized Phase III WSG Plan B Trial Comparing 4xEC-4xDoc Versus 6xTC in Breast Cancer Patients with HER2 Negative Breast Cancer (BC).

Abstract Background: Anthracycline-taxane based adjuvant chemotherapy (cht) is considered standard in node-positive and high-risk node-negative BC. However, retrospective analyses suggest that in HER2−BC, benefit from anthracyclines may not outweigh acute and long term toxicities. Recurrence Score (RS) identifies patients who are not candidates for cht based on their low relapse risk, as well as minimal, if any, benefit of cht. The WSG Plan B trial investigates anthracycline-free cht in HER2− BC and is the first trial in Europe prospectively incorporating RS for decision making regarding adjuvant cht in both N0 and N+ BC. Methods: Plan B trial randomizes HER2− BC patients with high-risk N0 (at least one risk factor: ≥pT2; negative HR status; G2-3; age ≤35 years old; high uPA/PAI-1) or N+ disease to 6xTC (Docetaxel 75Cyclophosphomide600) vs. 4xEC (Epirubicin90Cyclophosphomide600)-4xDocetaxel100 G-CSF prophylaxis is recommended according to current ASCO guidelines. The statistical design previews n=2.448 randomized to cht; patients with HR+ BC, N0-3 and a RS ≤11 receive endocrine therapy only. Results: From April 2009 to June 2011, 3037 patients have been recruited and 2296 randomized (TC/EC-Doc: 1146/1150; age &amp;lt;65 years old: 900/911; ≥65 years old: 246/239). From the patients with HR+ disease (n=2368) 18% had a RS 0–11, 61% a RS 12–25 and 21% a RS ≥ 25. In patients with 0–3 positive LN and RS of 0–11 (n=329) who opted for no cht 257 are in the observational arm. In the group with an intermediate risk (RS 12–25) 14% drop outs before start of cht have been reported. In 1172 fully monitored patients 22 toxicity-related therapy stops have been reported in the TC and 34 in the EC-Doc arm (p=0.12). 614 serious adverse events (SAE) have been reported (299 TC vs. 315 EC-Doc). There is no difference in patients &amp;lt;65 years old (TC vs. EC-Doc: 218/218), but slightly more SAE's in patients ≥65 years old treated by EC-Doc (97 vs. 81, p=0.13). The most frequent SAEs were: leucopenia, febrile neutropenia (TC/EC-Doc:37 (3.3%)/31 (2.7%), n.s.), infections and heart/vascular events (TC/EC-Doc 29/40, n.s.). In patients ≥65 years old, there is a trend towards more febrile neutropenia (13 vs. 5; p=0.06) in the TC, and more severe mucositis/diarrhea/nausea (3 vs. 15; p=0.007) and heart/vascular events (5 vs. 14; p=0.06) in the EC-Doc arm. There were 5 therapy related deaths (TC 5 (0.4%)/EC-Doc 0, p=0.03); 3 in patients &amp;lt;65 years, 2 in patients ≥65 years (4 due to sepsis, 1 due to cardiac failure). Detailed data on relationship between the protocol specified, RS-guided treatment assignment and toxicity, and use of G-CSF support will be updated for the meeting. Conclusions: The Plan-B trial is one of the largest randomized phase III trials currently evaluating anthracycline-free adjuvant cht in HER2− BC. The cht administered within the study was generally well tolerated, but higher number of treatment-related deaths has been observed within the TC arm. The short term toxicity profile seems be different between both study arms, particularly in patients &amp;gt;65 years old. On the basis of prognosis as determined by RS, cht has been spared after a shared decision process in a substantial group of patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-18-03.